bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of experience in prioritizing hippocampal replay
Authors: Huelin Gorriz Marta , Takigawa Masahiro , Bendor Daniel
Published: December 2023

During sleep, recent memories are replayed by the hippocampus, leading to their consolidation, with a higher priority given to salient experiences. To examine the role of replay in the selective strengthening of memories, we recorded large ensembles of hippocampal place cells while male rats ran repeated spatial trajectories on two linear tracks, differing in either their familiarity or number of laps run. We observed that during sleep, the rate of replay events for a given track increased proportionally with the number of spatial trajectories run by the animal. In contrast, the rate of sleep replay events decreased if the animal was more familiar with the track. Furthermore, we find that the cumulative number of awake replay events occurring during behavior, influenced by both the novelty and duration of an experience, predicts which memories are prioritized for sleep replay, providing a more parsimonious neural correlate for the selective strengthening of memories.
The NERP-4–SNAT2 axis regulates pancreatic β-cell maintenance and function
Authors: Zhang Weidong , Miura Ayako , Abu Saleh Md Moin , Shimizu Koichiro , Mita Yuichiro , Tanida Ryota , Hirako Satoshi , Shioda Seiji , Gmyr Valery , Kerr-Conte Julie , Pattou Francois , Jin Chunhuan , Kanai Yoshikatsu , Sasaki Kazuki , Minamino Naoto , Sakoda Hideyuki , Nakazato Masamitsu
Published: December 2023

Insulin secretion from pancreatic β cells is regulated by multiple stimuli, including nutrients, hormones, neuronal inputs, and local signalling. Amino acids modulate insulin secretion via amino acid transporters expressed on β cells. The granin protein VGF has dual roles in β cells: regulating secretory granule formation and functioning as a multiple peptide precursor. A VGF-derived peptide, neuroendocrine regulatory peptide-4 (NERP-4), increases Ca2+ influx in the pancreata of transgenic mice expressing apoaequorin, a Ca2+-induced bioluminescent protein complex. NERP-4 enhances glucose-stimulated insulin secretion from isolated human and mouse islets and β-cell–derived MIN6-K8 cells. NERP-4 administration reverses the impairment of β-cell maintenance and function in db/db mice by enhancing mitochondrial function and reducing metabolic stress. NERP-4 acts on sodium-coupled neutral amino acid transporter 2 (SNAT2), thereby increasing glutamine, alanine, and proline uptake into β cells and stimulating insulin secretion. SNAT2 deletion and inhibition abolish the protective effects of NERP-4 on β-cell maintenance. These findings demonstrate a novel autocrine mechanism of β-cell maintenance and function that is mediated by the peptide–amino acid transporter axis.
Itaconate promotes hepatocellular carcinoma progression by epigenetic induction of CD8+ T-cell exhaustion
Authors: Gu Xuemei , Wei Haoran , Suo Caixia , Shen Shengqi , Zhu Chuxu , Chen Liang , Yan Kai , Li Zhikun , Bian Zhenhua , Zhang Pinggen , Yuan Mengqiu , Yu Yingxuan , Du Jinzhi , Zhang Huafeng , Sun Linchong , Gao Ping
Published: December 2023

Itaconate is a well-known immunomodulatory metabolite; however, its role in hepatocellular carcinoma (HCC) remains unclear. Here, we find that macrophage-derived itaconate promotes HCC by epigenetic induction of Eomesodermin (EOMES)-mediated CD8+ T-cell exhaustion. Our results show that the knockout of immune-responsive gene 1 (IRG1), responsible for itaconate production, suppresses HCC progression. Irg1 knockout leads to a decreased proportion of PD-1+ and TIM-3+ CD8+ T cells. Deletion or adoptive transfer of CD8+ T cells shows that IRG1-promoted tumorigenesis depends on CD8+ T-cell exhaustion. Mechanistically, itaconate upregulates PD-1 and TIM-3 expression levels by promoting succinate-dependent H3K4me3 of the Eomes promoter. Finally, ibuprofen is found to inhibit HCC progression by targeting IRG1/itaconate-dependent tumor immunoevasion, and high IRG1 expression in macrophages predicts poor prognosis in HCC patients. Taken together, our results uncover an epigenetic link between itaconate and HCC and suggest that targeting IRG1 or itaconate might be a promising strategy for HCC treatment.
Amplified fluorogenic immunoassay for early diagnosis and monitoring of Alzheimer’s disease from tear fluid
Authors: Lee Sojeong , Kim Eunjung , Moon Chae-Eun , Park Chaewon , Lim Jong-Woo , Baek Minseok , Shin Moo-Kwang , Ki Jisun , Cho Hanna , Ji Yong Woo , Haam Seungjoo
Published: December 2023

Accurate diagnosis of Alzheimer’s disease (AD) in its earliest stage can prevent the disease and delay the symptoms. Therefore, more sensitive, non-invasive, and simple screening tools are required for the early diagnosis and monitoring of AD. Here, we design a self-assembled nanoparticle-mediated amplified fluorogenic immunoassay (SNAFIA) consisting of magnetic and fluorophore-loaded polymeric nanoparticles. Using a discovery cohort of 21 subjects, proteomic analysis identifies adenylyl cyclase-associated protein 1 (CAP1) as a potential tear biomarker. The SNAFIA demonstrates a low detection limit (236 aM), good reliability (R2 = 0.991), and a wide analytical range (0.320–1000 fM) for CAP1 in tear fluid. Crucially, in the verification phase with 39 subjects, SNAFIA discriminates AD patients from healthy controls with 90% sensitivity and 100% specificity in under an hour. Utilizing tear fluid as a liquid biopsy, SNAFIA could potentially aid in long-term care planning, improve clinical trial efficiency, and accelerate therapeutic development for AD.
Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1
Authors: Asadollahi Kazem , Rajput Sunnia , de Zhang Lazarus Andrew , Ang Ching-Seng , Nie Shuai , Williamson Nicholas A. , Griffin Michael D. W. , Bathgate Ross A. D. , Scott Daniel J. , Weikl Thomas R. , Jameson Guy N. L. , Gooley Paul R.
Published: December 2023

The conformational ensembles of G protein-coupled receptors (GPCRs) include inactive and active states. Spectroscopy techniques, including NMR, show that agonists, antagonists and other ligands shift the ensemble toward specific states depending on the pharmacological efficacy of the ligand. How receptors recognize ligands and the kinetic mechanism underlying this population shift is poorly understood. Here, we investigate the kinetic mechanism of neurotensin recognition by neurotensin receptor 1 (NTS1) using 19F-NMR, hydrogen-deuterium exchange mass spectrometry and stopped-flow fluorescence spectroscopy. Our results indicate slow-exchanging conformational heterogeneity on the extracellular surface of ligand-bound NTS1. Numerical analysis of the kinetic data of neurotensin binding to NTS1 shows that ligand recognition follows an induced-fit mechanism, in which conformational changes occur after neurotensin binding. This approach is applicable to other GPCRs to provide insight into the kinetic regulation of ligand recognition by GPCRs.
Senescence-associated 13-HODE production promotes age-related liver steatosis by directly inhibiting catalase activity
Authors: Duan Jinjie , Dong Wenhui , Wang Guangyan , Xiu Wenjing , Pu Guangyin , Xu Jingwen , Ye Chenji , Zhang Xu , Zhu Yi , Wang Chunjiong
Published: December 2023

Aging is a major risk factor for metabolic disorders. Polyunsaturated fatty acid-derived bioactive lipids play critical roles as signaling molecules in metabolic processes. Nonetheless, their effects on age-related liver steatosis remain unknown. Here we show that senescent liver cells induce liver steatosis in a paracrine manner. Linoleic acid-derived 9-hydroxy-octadecadienoic acid (9-HODE) and 13-HODE increase in middle-aged (12-month-old) and aged (20-month-old) male mouse livers and conditioned medium from senescent hepatocytes and macrophages. Arachidonate 15-lipoxygenase, an enzyme for 13-HODE and 9-HODE production, is upregulated in senescent cells. A 9-HODE and 13-HODE mixture induces liver steatosis and activates SREBP1. Furthermore, catalase (CAT) is a direct target of 13-HODE, and its activity is decreased by 13-HODE. CAT overexpression reduces 13-HODE-induced liver steatosis and protects male mice against age-related liver steatosis. Therefore, 13-HODE produced by senescent hepatocytes and macrophages activates SREBP1 by directly inhibiting CAT activity and promotes liver steatosis.
Harnessing PROTAC technology to combat stress hormone receptor activation
Authors: Gazorpak Mahshid , Hugentobler Karina M. , Paul Dominique , Germain Pierre-Luc , Kretschmer Miriam , Ivanova Iryna , Frei Selina , Mathis Kei , Rudolf Remo , Mompart Barrenechea Sergio , Fischer Vincent , Xue Xiaohan , Ptaszek Aleksandra L. , Holzinger Julian , Privitera Mattia , Hierlemann Andreas , Meijer Onno C. , Konrat Robert , Carreira Erick M. , Bohacek Johannes , Gapp Katharina
Published: December 2023

Counteracting the overactivation of glucocorticoid receptors (GR) is an important therapeutic goal in stress-related psychiatry and beyond. The only clinically approved GR antagonist lacks selectivity and induces unwanted side effects. To complement existing tools of small-molecule-based inhibitors, we present a highly potent, catalytically-driven GR degrader, KH-103, based on proteolysis-targeting chimera technology. This selective degrader enables immediate and reversible GR depletion that is independent of genetic manipulation and circumvents transcriptional adaptations to inhibition. KH-103 achieves passive inhibition, preventing agonistic induction of gene expression, and significantly averts the GR’s genomic effects compared to two currently available inhibitors. Application in primary-neuron cultures revealed the dependency of a glucocorticoid-induced increase in spontaneous calcium activity on GR. Finally, we present a proof of concept for application in vivo. KH-103 opens opportunities for a more lucid interpretation of GR functions with translational potential.
Structural and functional analysis of the minimal orthomyxovirus-like polymerase of Tilapia Lake Virus from the highly diverged Amnoonviridae family
Authors: Arragain Benoit , Pelosse Martin , Thompson Albert , Cusack Stephen
Published: December 2023

Tilapia Lake Virus (TiLV), a recently discovered pathogen of tilapia fish, belongs to the Amnoonviridae family from the Articulavirales order. Its ten genome segments have characteristic conserved ends and encode proteins with no known homologues, apart from the segment 1, which encodes an orthomyxo-like RNA-dependent-RNA polymerase core subunit. Here we show that segments 1–3 encode respectively the PB1, PB2 and PA-like subunits of an active heterotrimeric polymerase that maintains all domains found in the distantly related influenza polymerase, despite an unprecedented overall size reduction of 40%. Multiple high-resolution cryo-EM structures of TiLV polymerase in pre-initiation, initiation and active elongation states, show how it binds the vRNA and cRNA promoters and performs RNA synthesis, with both transcriptase and replicase configurations being characterised. However, the highly truncated endonuclease-like domain appears inactive and the putative cap-binding domain is autoinhibited, emphasising that many functional aspects of TiLV polymerase remain to be elucidated.
Structural insights into photosystem II supercomplex and trimeric FCP antennae of a centric diatom Cyclotella meneghiniana
Authors: Zhao Songhao , Shen Lili , Li Xiaoyi , Tao Qiushuang , Li Zhenhua , Xu Caizhe , Zhou Cuicui , Yang Yanyan , Sang Min , Han Guangye , Yu Long-Jiang , Kuang Tingyun , Shen Jian-Ren , Wang Wenda
Published: December 2023

Diatoms are dominant marine algae and contribute around a quarter of global primary productivity, the success of which is largely attributed to their photosynthetic capacity aided by specific fucoxanthin chlorophyll-binding proteins (FCPs) to enhance the blue-green light absorption under water. We purified a photosystem II (PSII)-FCPII supercomplex and a trimeric FCP from Cyclotella meneghiniana (Cm) and solved their structures by cryo-electron microscopy (cryo-EM). The structures reveal detailed organizations of monomeric, dimeric and trimeric FCP antennae, as well as distinct assemblies of Lhcx6_1 and dimeric FCPII-H in PSII core. Each Cm-PSII-FCPII monomer contains an Lhcx6_1, an FCP heterodimer and other three FCP monomers, which form an efficient pigment network for harvesting energy. More diadinoxanthins and diatoxanthins are found in FCPs, which may function to quench excess energy. The trimeric FCP contains more chlorophylls c and fucoxanthins. These diversified FCPs and PSII-FCPII provide a structural basis for efficient light energy harvesting, transfer, and dissipation in C. meneghiniana.
Total wash elimination for solid phase peptide synthesis
Authors: Collins Jonathan M. , Singh Sandeep K. , White Travis A. , Cesta Drew J. , Simpson Colin L. , Tubb Levi J. , Houser Christopher L.
Published: December 2023

We present a process for solid phase peptide synthesis (SPPS) that completely eliminates all solvent intensive washing steps during each amino acid addition cycle. A key breakthrough is the removal of a volatile Fmoc deprotection base through bulk evaporation at elevated temperature while preventing condensation on the vessel surfaces with a directed headspace gas flushing. This process was demonstrated at both research and production scales without any impact on product quality and when applied to a variety of challenging sequences (up to 89 amino acids in length). The overall result is an extremely fast, high purity, scalable process with a massive waste reduction (up to 95%) while only requiring 10–15% of the standard amount of base used. This transformation of SPPS represents a step-change in peptide manufacturing process efficiency, and should encourage expanded access to peptide-based therapeutics.
Genotoxic stress stimulates eDNA release via explosive cell lysis and thereby promotes streamer formation of Burkholderia cenocepacia H111 cultured in a microfluidic device
Authors: Heredia-Ponce Zaira , Secchi Eleonora , Toyofuku Masanori , Marinova Gabriela , Savorana Giovanni , Eberl Leo
Published: December 2023

DNA is a component of biofilms, but the triggers of DNA release during biofilm formation and how DNA contributes to biofilm development are poorly investigated. One key mechanism involved in DNA release is explosive cell lysis, which is a consequence of prophage induction. In this article, the role of explosive cell lysis in biofilm formation was investigated in the opportunistic human pathogen Burkholderia cenocepacia H111 (H111). Biofilm streamers, flow-suspended biofilm filaments, were used as a biofilm model in this study, as DNA is an essential component of their matrix. H111 contains three prophages on chromosome 1 of its genome, and the involvement of each prophage in causing explosive cell lysis of the host and subsequent DNA and membrane vesicle (MV) release, as well as their contribution to streamer formation, were studied in the presence and absence of genotoxic stress. The results show that two of the three prophages of H111 encode functional lytic prophages that can be induced by genotoxic stress and their activation causes DNA and MVs release by explosive cell lysis. Furthermore, it is shown that the released DNA enables the strain to develop biofilm streamers, and streamer formation can be enhanced by genotoxic stress. Overall, this study demonstrates the involvement of prophages in streamer formation and uncovers an often-overlooked problem with the use of antibiotics that trigger the bacterial SOS response for the treatment of bacterial infections.
Space microgravity increases expression of genes associated with proliferation and differentiation in human cardiac spheres
Authors: Hwang Hyun , Rampoldi Antonio , Forghani Parvin , Li Dong , Fite Jordan , Boland Gene , Maher Kevin , Xu Chunhui
Published: December 2023

Efficient generation of cardiomyocytes from human-induced pluripotent stem cells (hiPSCs) is important for their application in basic and translational studies. Space microgravity can significantly change cell activities and function. Previously, we reported upregulation of genes associated with cardiac proliferation in cardiac progenitors derived from hiPSCs that were exposed to space microgravity for 3 days. Here we investigated the effect of long-term exposure of hiPSC-cardiac progenitors to space microgravity on global gene expression. Cryopreserved 3D hiPSC-cardiac progenitors were sent to the International Space Station (ISS) and cultured for 3 weeks under ISS microgravity and ISS 1 G conditions. RNA-sequencing analyses revealed upregulation of genes associated with cardiac differentiation, proliferation, and cardiac structure/function and downregulation of genes associated with extracellular matrix regulation in the ISS microgravity cultures compared with the ISS 1 G cultures. Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes mapping identified the upregulation of biological processes, molecular function, cellular components, and pathways associated with cell cycle, cardiac differentiation, and cardiac function. Taking together, these results suggest that space microgravity has a beneficial effect on the differentiation and growth of cardiac progenitors.
Sentence completion in progressive supranuclear palsy following transcranial direct current stimulation
Authors: Scholtz Johanna , Weiss Sabine , Redecker Christoph , Müller Horst M.
Published: December 2023

Progressive supranuclear palsy (PSP) is an atypical Parkinsonian disorder which results in deterioration of motor and cognitive skills, including language disorders such as impaired word retrieval. While there is evidence of successful use of tDCS to improve word fluency in PSP, little is known about the effectiveness of brain stimulation for word retrieval in sentence context. Therefore, we investigated whether tDCS reduces sentence completion time in PSP patients. In this sham-controlled, triple-blinded crossover study, anodal tDCS (atDCS) was applied over the left Broca’s area at 2 mA for 20 min (n = 23). In contrast to patients with multiple system atrophy (MSA), also an atypical Parkinsonian disorder, and healthy elderlies, sentence completion improved in PSP patients when tDCS was applied. The improvement in word fluency reported in previous studies using other electrode positions was not replicated. By using atDCS of the left Broca’s area, we were able to demonstrate a difference between the two movement disorders. The obtained insight could be helpful to improve language therapy of these disorders.
Pharmaco-EEG of antipsychotic treatment response: a systematic review
Authors: De Pieri Marco , Rochas Vincent , Sabe Michel , Michel Cristoph , Kaiser Stefan
Published: December 2023

Response to antipsychotic medications (AP) is subjected to a wide and unpredictable variability and efforts were directed to discover predictive biomarkers to personalize treatment. Electroencephalography abnormalities in subjects with schizophrenia are well established, as well as a pattern of EEG changes induced by APs. The aim of this review is to provide a synthesis of the EEG features that are related to AP efficacy, including both pre-treatment signatures and changes induced by APs during treatment. A systematic review of English articles using PubMed, PsychINFO and the Cochrane database of systematic reviews was undertaken until july 2023. Additional studies were added by hand search. Studies having as an endpoint the relationship between AP-related clinical improvement and electroencephalographic features were included. Heterogeneity prevented a quantitative synthesis. Out of 1232 records screened, 22 studies were included in a final qualitative synthesis. Included studies evaluated resting-state and task-related power spectra, functional connectivity, microstates and epileptic abnormalities. At pre-treatment resting-state EEG, the most relevant predictors of a poor response were a change in theta power compared to healthy control, a high alpha power and connectivity, and diminished beta power. Considering EEG during treatment, an increased theta power, a reduced beta-band activity, an increased alpha activity, a decreased coherence in theta, alpha and beta-band were related to a favorable outcome. EEG is promising as a method to create a predictive biomarker for response to APs; further investigations are warranted to harmonize and generalize the contradictory results of reviewed studies.
A Drosophila heart optical coherence microscopy dataset for automatic video segmentation
Authors: Fishman Matthew , Matt Abigail , Wang Fei , Gracheva Elena , Zhu Jiantao , Ouyang Xiangping , Komarov Andrey , Wang Yuxuan , Liang Hongwu , Zhou Chao
Published: December 2023

The heart of the fruit fly, Drosophila melanogaster, is a particularly suitable model for cardiac studies. Optical coherence microscopy (OCM) captures in vivo cross-sectional videos of the beating Drosophila heart for cardiac function quantification. To analyze those large-size multi-frame OCM recordings, human labelling has been employed, leading to low efficiency and poor reproducibility. Here, we introduce a robust and accurate automated Drosophila heart segmentation algorithm, called FlyNet 2.0+, which utilizes a long short-term memory (LSTM) convolutional neural network to leverage time series information in the videos, ensuring consistent, high-quality segmentation. We present a dataset of 213 Drosophila heart videos, equivalent to 604,000 cross-sectional images, containing all developmental stages and a wide range of beating patterns, including faster and slower than normal beating, arrhythmic beating, and periods of heart stop to capture these heart dynamics. Each video contains a corresponding ground truth mask. We expect this unique large dataset of the beating Drosophila heart in vivo will enable new deep learning approaches to efficiently characterize heart function to advance cardiac research.
An innovative optics lab design for residency training in ophthalmology
Authors: Alipour Fateme , Samavati Katayoon , Abdi Parisa , Shirazi Mandana , Tavassoly Mohammad Taghi
Published: December 2023

Proper understanding of the optical function of the eye is the foundation of clinical understanding of ophthalmologists. Although teaching principals of optics has always been a part of ophthalmology residency curriculum, it seems that successful strategies other than lecture—based methods are needed to engage students and facilitate the understanding of optical principals. A collaborative team of physicists (optics Ph.D.), ophthalmologists and medical education experts designed an optics lab for ophthalmology residents to help them practically simulate different optical phenomena. The educational course consisted of 4 sessions of 90 min to practice the optical tests using the lab instruments. Each class consisted of 6–9 residents, divided into 3 groups with a fully equipped unit, and two mentors (an optics Ph.D. professor and an ophthalmology professor). A quasi-experimental design with pre-post test was used to evaluate the effectiveness of the training workshop in changing the ophthalmology residents’ optical knowledge and attitude. Thirty-five residents participated in the study. The average score of residents' performance before the workshop was 5.21 (out of 100), which increased significantly to 66.1 after the workshop. Also, the average knowledge of residents, which was measured as self-reported, increased significantly from 28.85 to 71.09. The average score of students' attitudes and interest was increased from 40.49 to 74.81. It seems that training workshops and labs are effective to bring about change in knowledge and attitude of ophthalmology residents toward optics as a new teaching strategy that would be implemented in their curriculum.
Streamlined instrument-free lysis for the detection of Candida auris
Authors: Jin Mei , Trick Alexander Y. , Totten Marissa , Lee Pei-wei , Zhang Sean X. , Wang Tza-Huei
Published: December 2023

The continued spread of Candida auris in healthcare facilities has increased the demand for widely available screening to aid in containment and inform treatment options. Current methods of detection can be unreliable and require bulky and expensive instruments to lyse and identify fungal pathogens. Here, we present a quick, low-cost, instrument-free method for lysis of C. auris suitable for streamlined sample processing with polymerase chain reaction (PCR) detection. Chemical, thermal, and bead beating lysis techniques were evaluated for lysis performance and compatibility with nucleic acid extraction and downstream PCR reactions. Using only 10 s of manual shaking with glass beads, this method demonstrated a limit of detection (LOD) of C. auris at 500 colony forming units per mL, a 20-fold improvement compared to the LOD without manual shaking, and a 60-fold reduction in time compared to common fungal lysis kits, all while maintaining repeatability and reproducibility across multiple users. This work highlights a simple method for increasing sensitivity and reducing turnaround time of PCR-based C. auris detection and exhibits promise for integration into point-of-care platforms towards real-time triage of colonized patients.
Foam formation during drainage of a surfactant solution in a microfluidic porous medium model
Authors: Lima Nicolle , Parsa Shima , Paciornik Sidnei , Carvalho Marcio S.
Published: December 2023

Foam has been shown to have great potential to significantly improve sweep efficiency during gas injection in oil recovery, remediation of contaminated sites, gas storage, and acidification processes. The gas mobility reduction largely depends on the generation and stability of lamellae in the pore space that traps the gas phase. Most available analyses focus on foam formation during the co-injection of gas and liquid phases at different fractional flow (foam quality) or flow of foam formed before being injected in the porous media. During surfactant-alternating-gas (SAG) injection, foam is formed as the aqueous phase is displaced by the gas slug that follows. The dynamics of lamellae formation and their stability are different from that of a co-injection process, since the amount of surfactant available to stabilize the gas-liquid interfaces is fixed as fresh surfactant solution is not injected together with the gas phase. This work studies foam formation during the drainage of a surfactant solution by gas injection at a fixed flow rate. A transparent microfluidic model of a porous medium is used in order to enable the correlation of pore-scale phenomena and macroscopic flow behavior. The results show that the maximum number of lamellae increases with surfactant concentration, even much above the critical micelle concentration (CMC). The availability of surfactant molecules needed to stabilize newly formed gas-liquid interfaces rises with concentration. The higher number of lamellae formed at higher surfactant concentration leads to stronger mobility reduction of the gas phase and longer time needed for the gas to percolate through the porous medium.
The effects of challenge or social buffering on cortisol, testosterone, and antler growth in captive red deer (Cervus elaphus) males
Authors: Bartoš Luděk , Esattore Bruno , Kotrba Radim , Pluháček Jan , Ceacero Francisco , Komárková Martina , Dušek Adam , Bartošová Jitka
Published: December 2023

We equipped 17 captive red deer males (Cervus elaphus) with GPS collars to measure inter-individual distances throughout the 5-months of the antler growth period. We expected some individuals to associate regularly with others while others would not. We predicted that males aggregating with others within a socially stable environment (Associates) would benefit from a form of “social buffering” and would likely have lowered cortisol (C) and testosterone (T) concentrations. Males only irregularly joining social groupings would experience elevated levels of aggression; according to the “Challenge hypothesis”, their T and C concentrations should increase. Interacting with a higher proportion of Associates did indeed reduce C concentrations. Conversely, avoiding Associates and challenging other males stimulated the T secretion. Admittedly, males avoiding regular proximity to others tended to develop the largest antlers. They probably benefited from frequent successful agonistic threats to conspecifics, resulting in elevated T concentrations. Regular association with tolerant, conspecifics and “social buffering” did not seem sufficient for producing larger antlers despite reducing C concentrations. Alternative social strategies were adopted within the same group of individuals and showed how the trade-off between these strategies could have an essential impact on C and T concentrations.
Oxidation-treated carbon nanotube yarns accelerate neurite outgrowth and induce axonal regeneration in peripheral nerve defect
Authors: Kunisaki Atsushi , Kodama Akira , Ishikawa Masakazu , Ueda Takahiro , Lima Marcio D. , Kondo Takeshi , Adachi Nobuo
Published: December 2023

Carbon nanotubes (CNTs) have the potential to promote peripheral nerve regeneration, although with limited capacity and foreign body reaction. This study investigated whether CNTs hydrophilized by oxidation can improve peripheral nerve regeneration and reduce foreign body reactions and inflammation. Three different artificial nerve conduit models were created using CNTs treated with ozone (O group), strong acid (SA group), and untreated (P group). They were implanted into a rat sciatic nerve defect model and evaluated after 8 and 16 weeks. At 16 weeks, the SA group showed significant recovery in functional and electrophysiological evaluations compared with the others. At 8 weeks, histological examination revealed a significant increase in the density of regenerated neurofilament and decreased foreign body giant cells in the SA group compared with the others. Oxidation-treated CNTs improved biocompatibility, induced nerve regeneration, and inhibited foreign-body reactions.
A multi-modal attention neural network for traffic flow prediction by capturing long-short term sequence correlation
Authors: Huang Xiaohui , Jiang Yuan , Wang Junyang , Lan Yuanchun , Chen Huapeng
Published: December 2023

Accurate traffic flow prediction information can help traffic managers and drivers make more rational decisions and choices. To make an effective and accurate traffic flow prediction, we need to consider not only the spatio-temporal dependencies between data, but also the temporal correlation between data. However, most existing methods only consider temporal continuity and ignore temporal correlation. In this paper, we propose a multi-modal attention neural network for traffic flow prediction by capturing long-short term sequence correlation (LSTSC). In the model, we employed attention mechanisms to capture the spatio-temporal correlations of the sequences, and the model based on multiple decision forms demonstrated higher accuracy and reliability. The superiority of the model is demonstrated on two datasets, PeMS08 and PeMSD7(M), particularly for long-term predictions.
A bead-based multiplex assay covering all coronaviruses pathogenic for humans for sensitive and specific surveillance of SARS-CoV-2 humoral immunity
Authors: Stern Daniel , Meyer Tanja C. , Treindl Fridolin , Mages Hans Werner , Krüger Maren , Skiba Martin , Krüger Jan Philipp , Zobel Christian M. , Schreiner Maximilian , Grossegesse Marica , Rinner Thomas , Peine Caroline , Stoliaroff-Pépin Anna , Harder Thomas , Hofmann Natalie , Michel Janine , Nitsche Andreas , Stahlberg Silke , Kneuer Antje , Sandoni Anna , Kubisch Ulrike , Schlaud Martin , Mankertz Annette , Schwarz Tatjana , Corman Victor M. , Müller Marcel A. , Drosten Christian , de la Rosa Kathrin , Schaade Lars , Dorner Martin B. , Dorner Brigitte G.
Published: December 2023

Serological assays measuring antibodies against SARS-CoV-2 are key to describe the epidemiology, pathobiology or induction of immunity after infection or vaccination. Of those, multiplex assays targeting multiple antigens are especially helpful as closely related coronaviruses or other antigens can be analysed simultaneously from small sample volumes, hereby shedding light on patterns in the immune response that would otherwise remain undetected. We established a bead-based 17-plex assay detecting antibodies targeting antigens from all coronaviruses pathogenic for humans: SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV strains 229E, OC43, HKU1, and NL63. The assay was validated against five commercial serological immunoassays, a commercial surrogate virus neutralisation test, and a virus neutralisation assay, all targeting SARS-CoV-2. It was found to be highly versatile as shown by antibody detection from both serum and dried blot spots and as shown in three case studies. First, we followed seroconversion for all four endemic HCoV strains and SARS-CoV-2 in an outbreak study in day-care centres for children. Second, we were able to link a more severe clinical course to a stronger IgG response with this 17-plex-assay, which was IgG1 and IgG3 dominated. Finally, our assay was able to discriminate recent from previous SARS-CoV-2 infections by calculating the IgG/IgM ratio on the N antigen targeting antibodies. In conclusion, due to the comprehensive method comparison, thorough validation, and the proven versatility, our multiplex assay is a valuable tool for studies on coronavirus serology.
SOCS2 inhibits hepatoblastoma metastasis via downregulation of the JAK2/STAT5 signal pathway
Authors: Lv Yong , Xie Xiaolong , Zou Guoyou , Kong Meng , Yang Jiayin , Chen Jing , Xiang Bo
Published: December 2023

Metastasis of hepatoblastoma (HB) is a key factor that impairs the prognosis and treatment of children. The suppressor of cytokine signaling 2 (SOCS2) is a classical negative feedback protein that regulates cytokine signal transduction and has been known to be downregulated in several tumor, but the molecular mechanisms of its involvement in HB metastasis are unknown. We found that SOCS2 was a gene down-regulated in hepatoblastoma and associated with HB metastasis through bioinformatics. The qRT-PCR, Western blot and IHC showed that SOCS2 was significantly lower in HB tissues. Clinicopathological correlation analysis revealed that low expression of SOCS2 was significantly correlated with tumor metastasis (P = 0.046) and vascular invasion (P = 0.028), associated with poor prognosis. Overexpression of SOCS2 inhibited the migration and invasion of hepatoblastoma cells, while knockdown of SOCS2 expression promoted these malignant phenotypes. In vivo studies revealed overexpression of SOCS2 inhibited the formation of lung metastasis. Up-regulation of SOCS2 in HB cell inhibited EMT and JAK2/STAT5. Conversely, down-regulation of SOCS2 promoted EMT and JAK2/STAT5. The addition of the JAK2 inhibitor Fedratinib partially reversed the effects of si-SOCS2 on HB cells. SOCS2 may inhibit the migration and invasion of HB cells by inhibiting the JAK2/STAT5 signaling pathway. These results may provide guiding significance for the clinical treatment of HB.
Source diversity of Artemia enrichment boosts goldfish (Carassius auratus) performance, β-carotene content, pigmentation, immune-physiological and transcriptomic responses
Authors: Elshafey Ahmed E. , Khalafalla Malik M. , Zaid Attia A. Abou , Mohamed Radi A. , Abdel-Rahim Mohamed M.
Published: December 2023

This study aimed to assess the impact of spirulina and/or canthaxanthin-enriched Artemia on the goldfish (Carassius auratus) growth, pigmentation, blood analysis, immunity, intestine and liver histomorphology, and expression of somatolactin (SL) and growth hormone (GH) genes. Artemia was enriched with spirulina and/or canthaxanthin for 24 h. Goldfish (N = 225, 1.10 ± 0.02 g) were tested in five experimental treatments, three replicates each: (T1) fish fed a commercial diet; (T2) fish fed a commercial diet and un-enriched Artemia (UEA); (T3) fish fed a commercial diet and spirulina-enriched Artemia (SEA); (T4) fish fed a commercial diet and canthaxanthin-enriched Artemia (CEA); and (T5) fish fed a commercial diet and spirulina and canthaxanthin-enriched Artemia (SCA) for 90 days. The results showed that the use of spirulina and/or canthaxanthin increased performance, β-carotene content and polyunsaturated fatty acids of Artemia. For goldfish, T5 showed the highest growth performance, β-carotene concentration and the lowest chromatic deformity. T5 also showed improved hematology profile, serum biochemical, and immunological parameters. Histomorphology of the intestine revealed an increase in villi length and goblet cells number in the anterior and middle intestine, with normal liver structure in T5. SL and GH gene expression in the liver and brain differed significantly among treatments with a significant increase in enriched Artemia treatments compared to T1 and T2. In conclusion, the use of spirulina and/or canthaxanthin improved performance of Artemia. Feeding goldfish spirulina and/or canthaxanthin-enriched Artemia improved performance, β-carotene content, pigmentation, health status and immune-physiological response.
Genome sequence and characterization of a novel Pseudomonas putida phage, MiCath
Authors: Jaryenneh James , Schoeniger Joseph S. , Mageeney Catherine M.
Published: December 2023

Pseudomonads are ubiquitous bacteria with importance in medicine, soil, agriculture, and biomanufacturing. We report a novel Pseudomonas putida phage, MiCath, which is the first known phage infecting P. putida S12, a strain increasingly used as a synthetic biology chassis. MiCath was isolated from garden soil under a tomato plant using P. putida S12 as a host and was also found to infect four other P. putida strains. MiCath has a ~ 61 kbp double-stranded DNA genome which encodes 97 predicted open reading frames (ORFs); functions could only be predicted for 48 ORFs using comparative genomics. Functions include structural phage proteins, other common phage proteins (e.g., terminase), a queuosine gene cassette, a cas4 exonuclease, and an endosialidase. Restriction digestion analysis suggests the queuosine gene cassette encodes a pathway capable of modification of guanine residues. When compared to other phage genomes, MiCath shares at most 74% nucleotide identity over 2% of the genome with any sequenced phage. Overall, MiCath is a novel phage with no close relatives, encoding many unique gene products.
Predicting the hyperelastic properties of alginate-gelatin hydrogels and 3D bioprinted mesostructures
Authors: Soufivand Anahita Ahmadi , Budday Silvia
Published: December 2023

Additive manufacturing has been widely used in tissue engineering, as 3D bioprinting enables fabricating geometrically complicated replacements for different tissues and organs. It is vital that the replacement mimics the specific properties of native tissue and bears the mechanical loading under its physiological conditions. Computational simulations can help predict and tune the mechanical properties of the printed construct—even before fabrication. In this study, we use the finite element (FE) method to predict the mechanical properties of different hydrogel mesostructures fabricated through various print patterns and validate our results through corresponding experiments. We first quantify the mechanical properties of alginate-gelatin hydrogels used as matrix material through an inverse approach using an FE model and cyclic compression-tension experimental data. Our results show that the fabrication process can significantly affect the material properties so that particular caution needs to be paid when calibrating FE models. We validate our optimized FE model using experimental data and show that it can predict the mechanical properties of different mesostructures, especially under compressive loading. The validated model enables us to tune the mechanical properties of different printed structures before their actual fabrication. The presented methodology can be analogously extended for cell bioprinting applications, other materials, and loading conditions. It can help save time, material, and cost for biofabrication applications in the future.
Pan msr gene deleted strain of Salmonella Typhimurium suffers oxidative stress, depicts macromolecular damage and attenuated virulence
Authors: Sahoo Raj , Chauhan Tapan Kumar Singh , Lalhmangaihzuali Lalhmangaihzuali , Sinha Esha , Qureshi Salauddin , Mahawar Manish
Published: December 2023

Salmonella encounters but survives host inflammatory response. To defend host-generated oxidants, Salmonella encodes primary antioxidants and protein repair enzymes. Methionine (Met) residues are highly prone to oxidation and convert into methionine sulfoxide (Met-SO) which compromises protein functions and subsequently cellular survival. However, by reducing Met-SO to Met, methionine sulfoxide reductases (Msrs) enhance cellular survival under stress conditions. Salmonella encodes five Msrs which are specific for particular Met-SO (free/protein bound), and ‘R’/‘S’ types. Earlier studies assessed the effect of deletions of one or two msrs on the stress physiology of S. Typhimurium. We generated a pan msr gene deletion (Δ5msr) strain in S. Typhimurium. The Δ5msr mutant strain shows an initial lag in in vitro growth. However, the Δ5msr mutant strain depicts very high sensitivity (p < 0.0001) to hypochlorous acid (HOCl), chloramine T (ChT) and superoxide-generating oxidant paraquat. Further, the Δ5msr mutant strain shows high levels of malondialdehyde (MDA), protein carbonyls, and protein aggregation. On the other side, the Δ5msr mutant strain exhibits lower levels of free amines. Further, the Δ5msr mutant strain is highly susceptible to neutrophils and shows defective fitness in the spleen and liver of mice. The results of the current study suggest that the deletions of all msrs render S. Typhimurium highly prone to oxidative stress and attenuate its virulence.
Synergistic effect of cryptotanshinone and temozolomide treatment against human glioblastoma cells
Authors: Zhu Songxian , Guo Jingjing , Yu Li , Liu Jun , Chen Jixiang , Xin Jinxin , Zhang Yuqiang , Luo Jie , Duan Chao
Published: December 2023

Glioblastoma multiforme (GBM) is a complex disease to treat owing to its profound chemoresistance. Therefore, we evaluated the combined effect and therapeutic efficacy of temozolomide (TMZ), a potent alkylating agent and the current gold standard therapy for GBM, and cryptotanshinone (CTS), which inhibits glioma cell proliferation in GBM cells. Using LN229 and U87-MG human GBM cells in a short-term stimulation in vitro model, the cytotoxic and anti-proliferative effects of single and combined treatment with 4 μM CTS and 200 μM TMZ were investigated. Furthermore, cell viability, DNA damage, apoptosis rate, and signal transducer and activator of transcription 3 (STAT3) protein were measured using cytotoxic assay, comet assay, flow cytometry, and western blotting analysis, respectively. The two drugs’ synergistic interaction was validated using the synergy score. We found that the anti-proliferative effects of combination therapy using the two drugs were greater than that of each agent used alone (CTS or TMZ). Western blot analysis indicated that treatment of GBM cells with CTS combined with TMZ more significantly decreased the expression of MGMT and STAT3, than that with TMZ alone. Combined treatment with CTS and TMZ might be an effective option to overcome the chemoresistance of GBM cells in a long-term treatment strategy.
Clarifying solvent effect during photocatalytic glycerol conversion on TiO2/GQD as selective photocatalyst
Authors: Hassan Sara , El-Hafiz Dalia R. Abd , Abdullah E. S. , Khalil Mostafa M. H.
Published: December 2023

Nowadays, dealing with the growing chemical and energy demands is important without compromising the environment. So, this work studies photocatalytic glycerol conversion (as biomass derivativ feedstock) into value-added products using an eco-friendly synthesized catalyst. Graphene quantum dots (GQDs) were prepared from available/cheap precursors like glucose via the hydrothermal method and used as a support for TiO2. TiO2/GQDs were characterized via different analytical techniques, revealing very small particle sizes of ~ 3–6 nm with a large surface area of ~ 253 m2/g and a band gap of ~ 2.6 eV. The prepared photocatalyst shows good efficiency during photocatalytic glycerol conversion to dihydroxyacetone (DHA). Different reaction conditions were tested: reaction time, catalyst amount, presence of oxidant (H2O2), and biphasic media (aqueous/organic phases). Comparing a monophasic (H2O) photoreactor with a biphasic reactor containing 90% organic phase (ethyl acetate) and 10% aqueous phase (H2O and/or H2O2) indicates that the presence of H2O2 increases glycerol conversion and liquid selectivity to reach 57% and 91%, respectively after 120 min. However, it still suffers a low DHA/GA ratio (2.7). On the other hand, using a biphasic reactor in the presence of an H2O2 oxidant increases the DHA/GA ratio to ~ 6.6, which was not reached in previous research. The formation of H2O/H2O2 as micro-reactors dispersed in the ethyl acetate phase increased the average light intensity effect of the glycerol/photocatalyst system in the micro-reactors. Unlike previous work, this work presents a facile way to prepare eco-friendly/cheap (noble metal free) photocatalysts for glycerol conversion to ultrapure DHA using a biphasic photoreactor.
Prediction of osteoporosis in patients with rheumatoid arthritis using machine learning
Authors: Lee Chaewon , Joo Gihun , Shin Seunghun , Im Hyeonseung , Moon Ki Won
Published: December 2023

Osteoporosis is a serious health concern in patients with rheumatoid arthritis (RA). Machine learning (ML) models have been increasingly incorporated into various clinical practices, including disease classification, risk prediction, and treatment response. However, only a few studies have focused on predicting osteoporosis using ML in patients with RA. We aimed to develop an ML model to predict osteoporosis using a representative Korean RA cohort database. The KORean Observational study Network for Arthritis (KORONA) database, established by the Clinical Research Center for RA in Korea, was used in this study. Among the 5077 patients registered in KORONA, 2374 patients were included in this study. Four representative ML algorithms were used for the prediction: logistic regression (LR), random forest, XGBoost (XGB), and LightGBM. The accuracy, F1 score, and area under the curve (AUC) of each model were measured. The LR model achieved the highest AUC value at 0.750, while the XGB model achieved the highest accuracy at 0.682. Body mass index, age, menopause, waist and hip circumferences, RA surgery, and monthly income were risk factors of osteoporosis. In conclusion, ML algorithms are a useful option for screening for osteoporosis in patients with RA.