bluuebunny/crossref_metadata_2025 huggingface dataset:
The matrisome landscape controlling in vivo germ cell fates
Authors: Amran Aqilah , Pigatto Lara , Farley Johanna , Godini Rasoul , Pocock Roger , Gopal Sandeep
Published: May 2024

The developmental fate of cells is regulated by intrinsic factors and the extracellular environment. The extracellular matrix (matrisome) delivers chemical and mechanical cues that can modify cellular development. However, comprehensive understanding of how matrisome factors control cells in vivo is lacking. Here we show that specific matrisome factors act individually and collectively to control germ cell development. Surveying development of undifferentiated germline stem cells through to mature oocytes in the Caenorhabditis elegans germ line enabled holistic functional analysis of 443 conserved matrisome-coding genes. Using high-content imaging, 3D reconstruction, and cell behavior analysis, we identify 321 matrisome genes that impact germ cell development, the majority of which (>80%) are undescribed. Our analysis identifies key matrisome networks acting autonomously and non-autonomously to coordinate germ cell behavior. Further, our results demonstrate that germ cell development requires continual remodeling of the matrisome landscape. Together, this study provides a comprehensive platform for deciphering how extracellular signaling controls cellular development and anticipate this will establish new opportunities for manipulating cell fates.
Cingulate microstimulation induces negative decision-making via reduced top-down influence on primate fronto-cingulo-striatal network
Authors: Amemori Satoko , Graybiel Ann M. , Amemori Ken-ichi
Published: May 2024

The dorsolateral prefrontal cortex (dlPFC) is crucial for regulation of emotion that is known to aid prevention of depression. The broader fronto-cingulo-striatal (FCS) network, including cognitive dlPFC and limbic cingulo-striatal regions, has been associated with a negative evaluation bias often seen in depression. The mechanism by which dlPFC regulates the limbic system remains largely unclear. Here we have successfully induced a negative bias in decision-making in female primates performing a conflict decision-making task, by directly microstimulating the subgenual cingulate cortex while simultaneously recording FCS local field potentials (LFPs). The artificially induced negative bias in decision-making was associated with a significant decrease in functional connectivity from cognitive to limbic FCS regions, represented by a reduction in Granger causality in beta-range LFPs from the dlPFC to the other regions. The loss of top-down directional influence from cognitive to limbic regions, we suggest, could underlie negative biases in decision-making as observed in depressive states.
Reduction of precious metal ions in aqueous solutions by contact-electro-catalysis
Authors: Su Yusen , Berbille Andy , Li Xiao-Fen , Zhang Jinyang , PourhosseiniAsl MohammadJavad , Li Huifan , Liu Zhanqi , Li Shunning , Liu Jianbo , Zhu Laipan , Wang Zhong Lin
Published: May 2024

Precious metals are core assets for the development of modern technologies in various fields. Their scarcity poses the question of their cost, life cycle and reuse. Recently, an emerging catalysis employing contact-electrification (CE) at water-solid interfaces to drive redox reaction, called contact-electro-catalysis (CEC), has been used to develop metal free mechano-catalytic methods to efficiently degrade refractory organic compounds, produce hydrogen peroxide, or leach metals from spent Li-Ion batteries. Here, we show ultrasonic CEC can successfully drive the reduction of Ag(ac), Rh3+, [PtCl4]2-, Ag+, Hg2+, Pd2+, [AuCl4]-, and Ir3+, in both anaerobic and aerobic conditions. The effect of oxygen on the reaction is studied by electron paramagnetic resonance (EPR) spectroscopy and ab-initio simulation. Combining measurements of charge transfers during water-solid CE, EPR spectroscopy and gold extraction experiments help show the link between CE and CEC. What’s more, this method based on water-solid CE is capable of extracting gold from synthetic solutions with concentrations ranging from as low as 0.196 ppm up to 196 ppm, reaching in 3 h extraction capacities ranging from 0.756 to 722.5 mg g−1 in 3 h. Finally, we showed CEC is employed to design a metal-free, selective, and recyclable catalytic gold extraction methods from e-waste aqueous leachates.
Ferritinophagy mediates adaptive resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer
Authors: Wang Hui , Hu Qianfan , Chen Yuzhong , Huang Xing , Feng Yipeng , Shi Yuanjian , Li Rutao , Yin Xuewen , Song Xuming , Liang Yingkuan , Zhang Te , Xu Lin , Dong Gaochao , Jiang Feng
Published: May 2024

Osimertinib (Osi) is a widely used epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). However, the emergence of resistance is inevitable, partly due to the gradual evolution of adaptive resistant cells during initial treatment. Here, we find that Osi treatment rapidly triggers adaptive resistance in tumor cells. Metabolomics analysis reveals a significant enhancement of oxidative phosphorylation (OXPHOS) in Osi adaptive-resistant cells. Mechanically, Osi treatment induces an elevation of NCOA4, a key protein of ferritinophagy, which maintains the synthesis of iron-sulfur cluster (ISC) proteins of electron transport chain and OXPHOS. Additionally, active ISC protein synthesis in adaptive-resistant cells significantly increases the sensitivity to copper ions. Combining Osi with elesclomol, a copper ion ionophore, significantly increases the efficacy of Osi, with no additional toxicity. Altogether, this study reveals the mechanisms of NCOA4-mediated ferritinophagy in Osi adaptive resistance and introduces a promising new therapy of combining copper ionophores to improve its initial efficacy.
Universal scaling in real dimension
Authors: Bighin Giacomo , Enss Tilman , Defenu Nicolò
Published: May 2024

The concept of universality has shaped our understanding of many-body physics, but is mostly limited to homogenous systems. Here, we present a study of universality on a non-homogeneous graph, the long-range diluted graph (LRDG). Its scaling theory is controlled by a single parameter, the spectral dimension ds, which plays the role of the relevant parameter on complex geometries. The graph under consideration allows us to tune the value of the spectral dimension continuously also to noninteger values and to find the universal exponents as continuous functions of the dimension. By means of extensive numerical simulations, we probe the scaling exponents of a simple instance of $$O({{{{{{{\mathcal{N}}}}}}}})$$
O

(

N

)

symmetric models on the LRDG showing quantitative agreement with the theoretical prediction of universal scaling in real dimensions.
Mycobacterium tuberculosis suppresses host antimicrobial peptides by dehydrogenating L-alanine
Authors: Peng Cheng , Cheng Yuanna , Ma Mingtong , Chen Qiu , Duan Yongjia , Liu Shanshan , Cheng Hongyu , Yang Hua , Huang Jingping , Bu Wenyi , Shi Chenyue , Wu Xiangyang , Chen Jianxia , Zheng Ruijuan , Liu Zhonghua , Ji Zhe , Wang Jie , Huang Xiaochen , Wang Peng , Sha Wei , Ge Baoxue , Wang Lin
Published: May 2024

Antimicrobial peptides (AMPs), ancient scavengers of bacteria, are very poorly induced in macrophages infected by Mycobacterium tuberculosis (M. tuberculosis), but the underlying mechanism remains unknown. Here, we report that L-alanine interacts with PRSS1 and unfreezes the inhibitory effect of PRSS1 on the activation of NF-κB pathway to induce the expression of AMPs, but mycobacterial alanine dehydrogenase (Ald) Rv2780 hydrolyzes L-alanine and reduces the level of L-alanine in macrophages, thereby suppressing the expression of AMPs to facilitate survival of mycobacteria. Mechanistically, PRSS1 associates with TAK1 and disruptes the formation of TAK1/TAB1 complex to inhibit TAK1-mediated activation of NF-κB pathway, but interaction of L-alanine with PRSS1, disables PRSS1-mediated impairment on TAK1/TAB1 complex formation, thereby triggering the activation of NF-κB pathway to induce expression of AMPs. Moreover, deletion of antimicrobial peptide gene β-defensin 4 (Defb4) impairs the virulence by Rv2780 during infection in mice. Both L-alanine and the Rv2780 inhibitor, GWP-042, exhibits excellent inhibitory activity against M. tuberculosis infection in vivo. Our findings identify a previously unrecognized mechanism that M. tuberculosis uses its own alanine dehydrogenase to suppress host immunity, and provide insights relevant to the development of effective immunomodulators that target M. tuberculosis.
Polyoxometalate-based plasmonic electron sponge membrane for nanofluidic osmotic energy conversion
Authors: Zhu Chengcheng , Xu Li , Liu Yazi , Liu Jiang , Wang Jin , Sun Hanjun , Lan Ya-Qian , Wang Chen
Published: May 2024

Nanofluidic membranes have demonstrated great potential in harvesting osmotic energy. However, the output power densities are usually hampered by insufficient membrane permselectivity. Herein, we design a polyoxometalates (POMs)-based nanofluidic plasmonic electron sponge membrane (PESM) for highly efficient osmotic energy conversion. Under light irradiation, hot electrons are generated on Au NPs surface and then transferred and stored in POMs electron sponges, while hot holes are consumed by water. The stored hot electrons in POMs increase the charge density and hydrophilicity of PESM, resulting in significantly improved permselectivity for high-performance osmotic energy conversion. In addition, the unique ionic current rectification (ICR) property of the prepared nanofluidic PESM inhibits ion concentration polarization effectively, which could further improve its permselectivity. Under light with 500-fold NaCl gradient, the maximum output power density of the prepared PESM reaches 70.4 W m−2, which is further enhanced even to 102.1 W m−2 by changing the ligand to P5W30. This work highlights the crucial roles of plasmonic electron sponge for tailoring the surface charge, modulating ion transport dynamics, and improving the performance of nanofluidic osmotic energy conversion.
The 8-17 DNAzyme can operate in a single active structure regardless of metal ion cofactor
Authors: Wieruszewska Julia , Pawłowicz Aleksandra , Połomska Ewa , Pasternak Karol , Gdaniec Zofia , Andrałojć Witold
Published: May 2024

DNAzymes – synthetic enzymes made of DNA — have long attracted attention as RNA-targeting therapeutic agents. Yet, as of now, no DNAzyme-based drug has been approved, partially due to our lacking understanding of their molecular mode of action. In this work we report the solution structure of 8–17 DNAzyme bound to a Zn2+ ion solved through NMR spectroscopy. Surprisingly, it turned out to be very similar to the previously solved Pb2+-bound form (catalytic domain RMSD = 1.28 Å), despite a long-standing literature consensus that Pb2+ recruits a different DNAzyme fold than other metal ion cofactors. Our follow-up NMR investigations in the presence of other ions — Mg2+, Na+, and Pb2+ – suggest that at DNAzyme concentrations used in NMR all these ions induce a similar tertiary fold. Based on these findings, we propose a model for 8–17 DNAzyme interactions with metal ions postulating the existence of only a single catalytically-active structure, yet populated to a different extent depending on the metal ion cofactor. Our results provide structural information on the 8-17 DNAzyme in presence of non-Pb2+ cofactors, including the biologically relevant Mg2+ ion.
An improved epigenetic counter to track mitotic age in normal and precancerous tissues
Authors: Zhu Tianyu , Tong Huige , Du Zhaozhen , Beck Stephan , Teschendorff Andrew E.
Published: May 2024

The cumulative number of stem cell divisions in a tissue, known as mitotic age, is thought to be a major determinant of cancer-risk. Somatic mutational and DNA methylation (DNAm) clocks are promising tools to molecularly track mitotic age, yet their relationship is underexplored and their potential for cancer risk prediction in normal tissues remains to be demonstrated. Here we build and validate an improved pan-tissue DNAm counter of total mitotic age called stemTOC. We demonstrate that stemTOC’s mitotic age proxy increases with the tumor cell-of-origin fraction in each of 15 cancer-types, in precancerous lesions, and in normal tissues exposed to major cancer risk factors. Extensive benchmarking against 6 other mitotic counters shows that stemTOC compares favorably, specially in the preinvasive and normal-tissue contexts. By cross-correlating stemTOC to two clock-like somatic mutational signatures, we confirm the mitotic-like nature of only one of these. Our data points towards DNAm as a promising molecular substrate for detecting mitotic-age increases in normal tissues and precancerous lesions, and hence for developing cancer-risk prediction strategies.
Evaluating the utility of multi-gene, multi-disease population-based panel testing accounting for uncertainty in penetrance estimates
Authors: Liang Jane W. , Christensen Kurt D. , Green Robert C. , Kraft Peter
Published: May 2024

Panel germline testing allows for the efficient detection of deleterious variants for multiple conditions, but the benefits and harms of identifying these variants are not always well understood. We present a multi-gene, multi-disease aggregate utility formula that allows the user to consider adding or removing each gene in a panel based on variant frequency, estimated penetrances, and subjective disutilities for testing positive but not developing the disease and testing negative but developing the disease. We provide credible intervals for utility that reflect uncertainty in penetrance estimates. Rare, highly penetrant deleterious variants tend to contribute positive net utilities for a wide variety of user-specified disutilities, even when accounting for parameter estimation uncertainty. However, the clinical utility of deleterious variants with moderate, uncertain penetrance depends more on assumed disutilities. The decision to include a gene on a panel depends on variant frequency, penetrance, and subjective utilities and should account for uncertainties around these factors.
Lysosomal and synaptic dysfunction markers in longitudinal cerebrospinal fluid of de novo Parkinson’s disease
Authors: Bartl Michael , Nilsson Johanna , Dakna Mohammed , Weber Sandrina , Schade Sebastian , Xylaki Mary , Fernandes Gomes Bárbara , Ernst Marielle , Muntean Maria-Lucia , Sixel-Döring Friederike , Trenkwalder Claudia , Zetterberg Henrik , Brinkmalm Ann , Mollenhauer Brit
Published: May 2024

Lysosomal and synaptic dysfunctions are hallmarks in neurodegeneration and potentially relevant as biomarkers, but data on early Parkinson’s disease (PD) is lacking. We performed targeted mass spectrometry with an established protein panel, assessing autophagy and synaptic function in cerebrospinal fluid (CSF) of drug-naïve de novo PD, and sex-/age-matched healthy controls (HC) cross-sectionally (88 PD, 46 HC) and longitudinally (104 PD, 58 HC) over 10 years. Multiple markers of autophagy, synaptic plasticity, and secretory pathways were reduced in PD. We added samples from prodromal subjects (9 cross-sectional, 12 longitudinal) with isolated REM sleep behavior disorder, revealing secretogranin-2 already decreased compared to controls. Machine learning identified neuronal pentraxin receptor and neurosecretory protein VGF as most relevant for discriminating between groups. CSF levels of LAMP2, neuronal pentraxins, and syntaxins in PD correlated with clinical progression, showing predictive potential for motor- and non-motor symptoms as a valid basis for future drug trials.
Large anomalous Hall effect in spin fluctuating devil’s staircase
Authors: Abe Naoki , Hano Yuya , Ishizuka Hiroaki , Kozuka Yusuke , Tadano Terumasa , Tsujimoto Yoshihiro , Yamaura Kazunari , Ishiwata Shintaro , Fujioka Jun
Published: May 2024

Electrons in metals can show a giant anomalous Hall effect (AHE) when interacting with characteristic spin texture. The AHE has been discussed in terms of scalar-spin-chirality (SSC) in long-range-ordered noncollinear spin textures typified by Skyrmion. The SSC becomes effective even in the paramagnetic state with thermal fluctuations, but the resultant AHE has been limited to be very small. Here, we report the observation of large AHE caused by the spin fluctuation near the devil’s staircase transition in a collinear antiferromagnetic metal SrCo6O11. The AHE is prominent near and above the transition temperature at moderate magnetic fields, where the anomalous Hall angle becomes the highest level among known oxide collinear ferromagnets/antiferromagnets (>2%). Furthermore, the anomalous Hall conductivity is quadratically scaled to the conductivity. These results imply that the thermally induced solitonic spin defects inherent to the devil’s staircase transition promote SSC-induced skew scattering.
A multi-omics approach for biomarker discovery in neuroblastoma: a network-based framework
Authors: Hussein Rahma , Abou-Shanab Ahmed M. , Badr Eman
Published: May 2024

Neuroblastoma (NB) is one of the leading causes of cancer-associated death in children. MYCN amplification is a prominent genetic marker for NB, and its targeting to halt NB progression is difficult to achieve. Therefore, an in-depth understanding of the molecular interactome of NB is needed to improve treatment outcomes. Analysis of NB multi-omics unravels valuable insight into the interplay between MYCN transcriptional and miRNA post-transcriptional modulation. Moreover, it aids in the identification of various miRNAs that participate in NB development and progression. This study proposes an integrated computational framework with three levels of high-throughput NB data (mRNA-seq, miRNA-seq, and methylation array). Similarity Network Fusion (SNF) and ranked SNF methods were utilized to identify essential genes and miRNAs. The specified genes included both miRNA-target genes and transcription factors (TFs). The interactions between TFs and miRNAs and between miRNAs and their target genes were retrieved where a regulatory network was developed. Finally, an interaction network-based analysis was performed to identify candidate biomarkers. The candidate biomarkers were further analyzed for their potential use in prognosis and diagnosis. The candidate biomarkers included three TFs and seven miRNAs. Four biomarkers have been previously studied and tested in NB, while the remaining identified biomarkers have known roles in other types of cancer. Although the specific molecular role is yet to be addressed, most identified biomarkers possess evidence of involvement in NB tumorigenesis. Analyzing cellular interactome to identify potential biomarkers is a promising approach that can contribute to optimizing efficient therapeutic regimens to target NB vulnerabilities.
Comprehensive molecular interaction map of TGFβ induced epithelial to mesenchymal transition in breast cancer
Authors: Gottumukkala Sai Bhavani , Ganesan Trivadi Sundaram , Palanisamy Anbumathi
Published: May 2024

Breast cancer is one of the prevailing cancers globally, with a high mortality rate. Metastatic breast cancer (MBC) is an advanced stage of cancer, characterised by a highly nonlinear, heterogeneous process involving numerous singling pathways and regulatory interactions. Epithelial–mesenchymal transition (EMT) emerges as a key mechanism exploited by cancer cells. Transforming Growth Factor-β (TGFβ)-dependent signalling is attributed to promote EMT in advanced stages of breast cancer. A comprehensive regulatory map of TGFβ induced EMT was developed through an extensive literature survey. The network assembled comprises of 312 distinct species (proteins, genes, RNAs, complexes), and 426 reactions (state transitions, nuclear translocations, complex associations, and dissociations). The map was developed by following Systems Biology Graphical Notation (SBGN) using Cell Designer and made publicly available using MINERVA (http://35.174.227.105:8080/minerva/?id=Metastatic_Breast_Cancer_1). While the complete molecular mechanism of MBC is still not known, the map captures the elaborate signalling interplay of TGFβ induced EMT-promoting MBC. Subsequently, the disease map assembled was translated into a Boolean model utilising CaSQ and analysed using Cell Collective. Simulations of these have captured the known experimental outcomes of TGFβ induced EMT in MBC. Hub regulators of the assembled map were identified, and their transcriptome-based analysis confirmed their role in cancer metastasis. Elaborate analysis of this map may help in gaining additional insights into the development and progression of metastatic breast cancer.
Enhanced photocatalytic performance of a rGO-Ca2Fe2O5 nanocomposite for photodegradation of emergent pollutants
Authors: Vavilapalli Durga Sankar , Qin Leiqiang , Palisaitis Justinas , Rosen Johanna
Published: May 2024

In this study, a simple thermal reduction process is used to synthesize a rGO-Ca2Fe2O5 (rGO-CFO) nanocomposite, with the morphological and optical characteristics of the CFO nanomaterial being modified by the rGO incorporation. The interface between rGO nanosheets and CFO nanoparticles facilitates efficient charge separation and resulting transfer of photogenerated charge carriers across the rGO nanosheets, demonstrated from photoluminescence and Mott-Schottky tests. Compared to CFO (2.1 eV), rGO-CFO has a reduced band gap energy of 1.9 eV. As synthesized nanocomposites were initially optimized and utilized for photodegradation of organic effluent Methylene blue (MB). An addition of 5 wt% rGO to the CFO demonstrated an improved photodegradation efficiency (97%) compared to bare CFO (72%). An active species trapping experiment was used to assess the MB photodegradation mechanism. The results demonstrate that hydroxyl radicals and holes are the major active species involved in photodegradation. The optimized composition (5rGO-CFO) was further tested for degradation of Bisphenol-A and Tetracycline (antibiotic). Altogether, these investigations show that the rGO-CFO is a highly efficient photocatalyst that can be used to remediate emerging contaminants in sunlight.
CheXmask: a large-scale dataset of anatomical segmentation masks for multi-center chest x-ray images
Authors: Gaggion Nicolás , Mosquera Candelaria , Mansilla Lucas , Saidman Julia Mariel , Aineseder Martina , Milone Diego H. , Ferrante Enzo
Published: May 2024

The development of successful artificial intelligence models for chest X-ray analysis relies on large, diverse datasets with high-quality annotations. While several databases of chest X-ray images have been released, most include disease diagnosis labels but lack detailed pixel-level anatomical segmentation labels. To address this gap, we introduce an extensive chest X-ray multi-center segmentation dataset with uniform and fine-grain anatomical annotations for images coming from five well-known publicly available databases: ChestX-ray8, CheXpert, MIMIC-CXR-JPG, Padchest, and VinDr-CXR, resulting in 657,566 segmentation masks. Our methodology utilizes the HybridGNet model to ensure consistent and high-quality segmentations across all datasets. Rigorous validation, including expert physician evaluation and automatic quality control, was conducted to validate the resulting masks. Additionally, we provide individualized quality indices per mask and an overall quality estimation per dataset. This dataset serves as a valuable resource for the broader scientific community, streamlining the development and assessment of innovative methodologies in chest X-ray analysis.
Evaluation of DNA yield from various tissue and sampling sources for use in single nucleotide polymorphism panels
Authors: Pearce David L. , Edson Jessie E. , Jennelle Chris S. , Walter W. David
Published: May 2024

Genetics studies are used by wildlife managers and researchers to gain inference into a population of a species of interest. To gain these insights, microsatellites have been the primary method; however, there currently is a shift from microsatellites to single nucleotide polymorphisms (SNPs). With the different DNA requirements between microsatellites and SNPs, an investigation into which samples can provide adequate DNA yield is warranted. Using samples that were collected from previous genetic projects from regions in the USA from 2014 to 2021, we investigated the DNA yield of eight sample categories to gain insights into which provided adequate DNA to be used in ddRADseq or already developed high- or medium-density SNP panels. We found seven sample categories that met the DNA requirements for use in all three panels, and one sample category that did not meet any of the three panels requirements; however, DNA integrity was highly variable and not all sample categories that met panel DNA requirements could be considered high quality DNA. Additionally, we used linear random-effects models to determine which covariates would have the greatest influence on DNA yield. We determined that all covariates (tissue type, storage method, preservative, DNA quality, time until DNA extraction and time after DNA extraction) could influence DNA yield.
Knowledge, attitudes, and practices towards urinary system stones among the Chengdu population
Authors: Lv Dong , Tang Liangyou , Chen Yongbo , Wang Rui , Liu Ling , Jian Nenghong , Zhang Ting , Shen Taimin
Published: May 2024

This cross-sectional study aimed to explore the knowledge, attitudes, and practices (KAP) regarding urinary system stones among the general public in Chengdu, China. Conducted between January and June 2023, this research targeted individuals undergoing physical examinations at the Health Management Center of Sichuan Provincial People's Hospital. Structured questionnaires were administered to collect demographic information and assess KAP related to urinary system stones. Following meticulous scrutiny, 1014 valid questionnaires were retained for analysis. The computed scores for knowledge, attitude, and practice were 9.36 ± 4.23 (possible score range 0–17), 37.75 ± 7.20 (possible score range 11–55), and 30.77 ± 4.00 (possible score range 10–50), respectively. These outcomes suggested insufficient knowledge and moderately positive attitudes and practices among the participants. Structural Equation Modeling (SEM) analysis revealed a direct impact of knowledge on attitude (β = 0.967, P < 0.001), with attitude subsequently exerting a direct influence on practice (β = 0.167, P < 0.001). This indicated an indirect impact of knowledge on practice. Additionally, there was a direct effect of knowledge on practice (β = 0.167, P < 0.001). In conclusion, the general populace in Chengdu exhibited insufficient knowledge and moderate attitudes and practices concerning urinary stones. These findings underscore the imperative for targeted educational interventions aimed at enhancing public awareness and fostering positive attitudes and practices toward urinary stone prevention and management.
Social interactions and olfactory cues are required for contagious itch in mice
Authors: Shayan Maryam , Haddadi Nazgol-Sadat , Shokrian Zeini Maryam , Shokrian Zeini Mohadese , Tashak Golroudbari Hasti , Afrooghe Arya , Ahmadi Elham , Rashki Asma , Dehpour Ahmad-Reza
Published: May 2024

The phenomenon of contagious itch, observed in both humans and rodents, remains a topic of ongoing debate concerning its modulators and underlying pathways. This study delves into the relationship between contagious itch and familiar olfactory cues, a non-visual factor contributing to this intriguing behavior. Our findings showed that contagious itch in observer mice occurs during physical interaction with the cagemate itch-demonstrator but not with a stranger demonstrator or in a non-physical encounter condition. Notably, itch-experienced observer mice displayed an increased contagious itch behavior, highlighting the relevance of itch-associated memory in this phenomenon. Furthermore, anosmic observer mice, whether itch-naïve or itch-experienced, displayed no contagious itch behavior. These results demonstrate that the familiar olfactory cues, specifically cagemate body odors, are required for contagious itch behaviors in mice. In line with these behavioral findings, our study reveals increased activity in brain regions associated with olfaction, emotion, and memory during contagious itch, including the olfactory bulb, the amygdala, the hypothalamus, and the hippocampus, with this activity diminished in anosmic mice. In conclusion, our study unveils the critical role of familiar olfactory cues in driving contagious itch in mice, shedding light on the interplay between social factors, sensory perception, and memory in this phenomenon.
Nucleobindin 2 inhibits senescence in gastric carcinoma
Authors: Ishibashi Yu , Itoh Takashi , Oguri Yasuko , Hashimura Miki , Yokoi Ako , Matsumoto Toshihide , Harada Yohei , Fukagawa Naomi , Hayashi Misato , Ono Mototsugu , Kusano Chika , Saegusa Makoto
Published: May 2024

Here, we focused on the role of Nucleobindin 2 (NUCB2), a multifunctional protein, in gastric carcinoma (GC) progression. NUCB2 expression was investigated in 150 GC cases (20 non-invasive (pT1) and 130 invasive (pT2/pT3/pT4) tumors) by immunohistochemistry (IHC), and in situ hybridization for detection of the mRNA in 21 cases. Using GC cell lines, we determined whether NUCB2 expression was associated with specific cellular phenotypes. In GC clinical samples, NUCB2 was transcriptionally upregulated when compared to normal tissues. High NUCB2 expression was associated with clinicopathological factors including deep tumor invasion, lymphovascular invasion, lymph node metastasis, and advanced clinical stages, and was a significant independent predictor of unfavorable progression-free survival in 150 non-invasive and invasive GC patients. Similar findings were also evident in 72 invasive GC cases in which patients received post-operative chemotherapy, but not in 58 invasive tumors from patients who did not receive the chemotherapy. In cell lines, NUCB2 knockout inhibited proliferation, susceptibility to apoptosis, and migration capability by inducting cellular senescence; this was consistent with higher proliferation and apoptotic indices in the NUCB2 IHC-high compared to NUCB2 IHC-low GC cases. NUCB2-dependent inhibition of senescence in GC engenders aggressive tumor behavior by modulating proliferation, apoptosis, and migration.
Preference of position in the proximity of various sugars revealed by location analysis of Drosophila melanogaster
Authors: Kato Haruki , Nakagawa Hiroyuki , Ishizaki Chiaki , Tomita Jun , Kume Kazuhiko
Published: May 2024

Feeding behaviors are determined by two main factors. One is the internal state, such as hunger or previous experiences; the other is external factors, such as sensory stimulation. During starvation, animals must balance food-seeking behavior with energy conservation. The fruit fly, Drosophila melanogaster, serves as a useful model for studying food selectivity and various behaviors related to food intake. However, few studies have directly connected food selectivity with other behaviors, such as locomotor activity and sleep. In this study, we report that flies exhibited a preference for specific positions and spent more time in the proximity of sweet sugars, such as sucrose and sucralose, but not non-sweet and nutritious sugars like xylitol and sorbitol. On the other hand, prolonged exposure to sorbitol increased the staying time of flies in the proximity of sorbitol. Additionally, after starvation, flies immediately exhibited a position preference in the proximity of sorbitol. These findings suggest that flies prefer the proximity of sweet food, and starvation alters their preference for nutritious food, which may be beneficial for their survival.
5-MeO-DMT induces sleep-like LFP spectral signatures in the hippocampus and prefrontal cortex of awake rats
Authors: Souza Annie C. , Souza Bryan C. , França Arthur , Moradi Marzieh , Souza Nicholy C. , Leão Katarina E. , Tort Adriano B. L. , Leão Richardson N. , Lopes-dos-Santos Vítor , Ribeiro Sidarta
Published: May 2024

5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent classical psychedelic known to induce changes in locomotion, behaviour, and sleep in rodents. However, there is limited knowledge regarding its acute neurophysiological effects. Local field potentials (LFPs) are commonly used as a proxy for neural activity, but previous studies investigating psychedelics have been hindered by confounding effects of behavioural changes and anaesthesia, which alter these signals. To address this gap, we investigated acute LFP changes in the hippocampus (HP) and medial prefrontal cortex (mPFC) of freely behaving rats, following 5-MeO-DMT administration. 5-MeO-DMT led to an increase of delta power and a decrease of theta power in the HP LFPs, which could not be accounted for by changes in locomotion. Furthermore, we observed a dose-dependent reduction in slow (20–50 Hz) and mid (50–100 Hz) gamma power, as well as in theta phase modulation, even after controlling for the effects of speed and theta power. State map analysis of the spectral profile of waking behaviour induced by 5-MeO-DMT revealed similarities to electrophysiological states observed during slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. Our findings suggest that the psychoactive effects of classical psychedelics are associated with the integration of waking behaviours with sleep-like spectral patterns in LFPs.
Directed biomechanical compressive forces enhance fusion efficiency in model placental trophoblast cultures
Authors: Parameshwar Prabu Karthick , Li Chen , Arnauts Kaline , Jiang Junqing , Rostami Sabra , Campbell Benjamin E. , Lu Hongyan , Rosenzweig Derek Hadar , Vaillancourt Cathy , Moraes Christopher
Published: May 2024

The syncytiotrophoblast is a multinucleated structure that arises from fusion of mononucleated cytotrophoblasts, to sheath the placental villi and regulate transport across the maternal–fetal interface. Here, we ask whether the dynamic mechanical forces that must arise during villous development might influence fusion, and explore this question using in vitro choriocarcinoma trophoblast models. We demonstrate that mechanical stress patterns arise around sites of localized fusion in cell monolayers, in patterns that match computational predictions of villous morphogenesis. We then externally apply these mechanical stress patterns to cell monolayers and demonstrate that equibiaxial compressive stresses (but not uniaxial or equibiaxial tensile stresses) enhance expression of the syndecan-1 and loss of E-cadherin as markers of fusion. These findings suggest that the mechanical stresses that contribute towards sculpting the placental villi may also impact fusion in the developing tissue. We then extend this concept towards 3D cultures and demonstrate that fusion can be enhanced by applying low isometric compressive stresses to spheroid models, even in the absence of an inducing agent. These results indicate that mechanical stimulation is a potent activator of cellular fusion, suggesting novel avenues to improve experimental reproductive modelling, placental tissue engineering, and understanding disorders of pregnancy development.
Synthesis and characterization of iron oxide nanoparticles from Lawsonia inermis and its effect on the biodegradation of crude oil hydrocarbon
Authors: Muthukumar Balakrishnan , Duraimurugan Ramanathan , Parthipan Punniyakotti , Rajamohan Rajaram , Rajagopal Rajakrishnan , Narenkumar Jayaraman , Rajasekar Aruliah , Malik Tabarak
Published: May 2024

Crude oil hydrocarbons are considered major environmental pollutants and pose a significant threat to the environment and humans due to having severe carcinogenic and mutagenic effects. Bioremediation is one of the practical and promising technology that can be applied to treat the hydrocarbon-polluted environment. In this present study, rhamnolipid biosurfactant (BS) produced by Pseudomonas aeruginosa PP4 and green synthesized iron nanoparticles (G-FeNPs) from Lawsonia inermis was used to evaluate the biodegradation efficiency (BE) of crude oil. The surface analysis of G-FeNPs was carried out by using FESEM and HRTEM to confirm the size and shape. Further, the average size of the G-FeNPs was observed around 10 nm by HRTEM analysis. The XRD and Raman spectra strongly confirm the presence of iron nanoparticles with their respective peaks. The BE (%) of mixed degradation system-V (PP4+BS+G-FeNPs) was obtained about 82%. FTIR spectrum confirms the presence of major functional constituents (C=O, –CH3, C–O, and OH) in the residual oil content. Overall, this study illustrates that integrated nano-based bioremediation could be an efficient approach for hydrocarbon-polluted environments. This study is the first attempt to evaluate the G-FeNPs with rhamnolipid biosurfactant on the biodegradation of crude oil.
Associations of coping and health-related behaviors with medical students’ well-being and performance during objective structured clinical examination
Authors: Barret Noémie , Guillaumée Théodore , Rimmelé Thomas , Cortet Marion , Mazza Stéphanie , Duclos Antoine , Rode Gilles , Lilot Marc , Schlatter Sophie
Published: May 2024

Objective structured clinical examination (OSCE) is a valid method to evaluate medical students’ competencies. The present cross-sectional study aimed at determining how students’ coping and health-related behaviors are associated with their psychological well-being and performance on the day of the OSCE. Fourth-year medical students answered a set of standardized questionnaires assessing their coping (BCI) and health-related behaviors before the examination (sleep PSQI, physical activity GPAQ). Immediately before the OSCE, they reported their level of instant psychological well-being on multi-dimensional visual analogue scales. OSCE performance was assessed by examiners blinded to the study. Associations were explored using multivariable linear regression models. A total of 482 students were included. Instant psychological well-being was positively associated with the level of positive thinking and of physical activity. It was negatively associated with the level of avoidance and of sleep disturbance. Furthermore, performance was negatively associated with the level of avoidance. Positive thinking, good sleep quality, and higher level of physical activity were all associated with improved well-being before the OSCE. Conversely, avoidance coping behaviors seem to be detrimental to both well-being and OSCE performance. The recommendation is to pay special attention to students who engage in avoidance and to consider implementing stress management programs.

Clinical trial: The study protocol was registered on clinicaltrial.gov NCT05393206, date of registration: 11 June 2022.
Interleukin-16 is increased in dialysis patients but is not a cardiovascular risk factor
Authors: Brösecke Frederic , Pfau Anja , Ermer Theresa , Dein Terra Mota Ribeiro Ana Beatriz , Rubenbauer Lisa , Rao Veena S. , Burlein Sarah , Genser Bernd , Reichel Martin , Aronson Peter S. , Coca Steven , Knauf Felix
Published: May 2024

Oxalate, a uremic toxin that accumulates in dialysis patients, is associated with cardiovascular disease. As oxalate crystals can activate immune cells, we tested the hypothesis that plasma oxalate would be associated with cytokine concentrations and cardiovascular outcomes in dialysis patients. In a cohort of 104 US patients with kidney failure requiring dialysis (cohort 1), we measured 21 inflammatory markers. As IL-16 was the only cytokine to correlate with oxalate, we focused further investigations on IL-16. We searched for associations between concentrations of IL-16 and mortality and cardiovascular events in the 4D cohort (1255 patients, cohort 2) and assessed further associations of IL-16 with other uremic toxins in this cohort. IL-16 levels were positively correlated with pOx concentrations (ρ = 0.39 in cohort 1, r = 0.35 in cohort 2) and were elevated in dialysis patients when compared to healthy individuals. No significant association could be found between IL-16 levels and cardiovascular events or mortality in the 4D cohort. We conclude that the cytokine IL-16 correlates with plasma oxalate concentrations and is substantially increased in patients with kidney failure on dialysis. However, no association could be detected between IL-16 concentrations and cardiovascular disease in the 4D cohort.
Chemogenetic activation or inhibition of histaminergic neurons bidirectionally modulates recognition memory formation and retrieval in male and female mice
Authors: Costa Alessia , Ducourneau Eva , Curti Lorenzo , Masi Alessio , Mannaioni Guido , Hardt Lola , Biyong Essi F. , Potier Mylène , Blandina Patrizio , Trifilieff Pierre , Provensi Gustavo , Ferreira Guillaume , Passani M. Beatrice
Published: May 2024

Several lines of evidence demonstrate that the brain histaminergic system is fundamental for cognitive processes and the expression of memories. Here, we investigated the effect of acute silencing or activation of histaminergic neurons in the hypothalamic tuberomamillary nucleus (TMNHA neurons) in vivo in both sexes in an attempt to provide direct and causal evidence of the necessary role of these neurons in recognition memory formation and retrieval. To this end, we compared the performance of mice in two non-aversive and non-rewarded memory tests, the social and object recognition memory tasks, which are known to recruit different brain circuitries. To directly establish the impact of inactivation or activation of TMNHA neurons, we examined the effect of specific chemogenetic manipulations during the formation (acquisition/consolidation) or retrieval of recognition memories. We consistently found that acute chemogenetic silencing of TMNHA neurons disrupts the formation or retrieval of both social and object recognition memory in males and females. Conversely, acute chemogenetic activation of TMNHA neurons during training or retrieval extended social memory in both sexes and object memory in a sex-specific fashion. These results suggest that the formation or retrieval of recognition memory requires the tonic activity of histaminergic neurons and strengthen the concept that boosting the brain histaminergic system can promote the retrieval of apparently lost memories.
Multidrug-resistant phenotypes of genetically diverse Escherichia coli isolates from healthy domestic cats
Authors: Núñez-Samudio Virginia , Pimentel-Peralta Gumercindo , De La Cruz Alexis , Landires Iván
Published: May 2024

Β-lactamases-producing Escherichia coli are a widely distributed source of antimicrobial resistance (AMR), for animals and humans. Little is known about the sensitivity profile and genetic characteristics of E. coli strains isolated from domestic cats. We report a cross-sectional study that evaluated E. coli strains isolated from domestic cats in Panama. For this study the following antibiotics were analyzed: ampicillin, amoxicillin-clavulanate cefepime, cefotaxime, cefoxitin, ceftazidime, aztreonam, imipenem, gentamicin, kanamycin, streptomycin, tetracycline, ciprofloxacin, nalidixic acid, trimethoprim-sulfamethoxazole, and chloramphenicol. The data obtained were classified as resistant, intermediate, or sensitive. MDR strains were established when the strain presented resistance to at least one antibiotic from three or more antimicrobial classes. Forty-eight E. coli isolates were obtained, of which 80% presented resistance to at least one of the antibiotics analyzed, while only 20% were sensitive to all (p = 0.0001). The most common resistance was to gentamicin (58%). Twenty-nine percent were identified as multidrug-resistant isolates and 4% with extended spectrum beta-lactamase phenotype. The genes blaTEM (39%), blaMOX(16%), blaACC (16%) and blaEBC (8%) were detected. Plasmid-mediated resistance qnrB (25%) and qnrA (13%) are reported. The most frequent sequence types (STs) being ST399 and we reported 5 new STs. Our results suggest that in intestinal strains of E. coli isolated from domestic cats there is a high frequency of AMR.
Assessment of TROP2, CEACAM5 and DLL3 in metastatic prostate cancer: Expression landscape and molecular correlates
Authors: Ajkunic Azra , Sayar Erolcan , Roudier Martine P. , Patel Radhika A. , Coleman Ilsa M. , De Sarkar Navonil , Hanratty Brian , Adil Mohamed , Zhao Jimmy , Zaidi Samir , True Lawrence D. , Sperger Jamie M. , Cheng Heather H. , Yu Evan Y. , Montgomery Robert B. , Hawley Jessica E. , Ha Gavin , Persse Thomas , Galipeau Patricia , Lee John K. , Harmon Stephanie A. , Corey Eva , Lang Joshua M. , Sawyers Charles L. , Morrissey Colm , Schweizer Michael T. , Gulati Roman , Nelson Peter S. , Haffner Michael C.
Published: May 2024

Therapeutic approaches targeting proteins on the surface of cancer cells have emerged as an important strategy for precision oncology. To capitalize on the potential impact of drugs targeting surface proteins, detailed knowledge about the expression patterns of the target proteins in tumor tissues is required. In castration-resistant prostate cancer (CRPC), agents targeting prostate-specific membrane antigen (PSMA) have demonstrated clinical activity. However, PSMA expression is lost in a significant number of CRPC tumors. The identification of additional cell surface targets is necessary to develop new therapeutic approaches. Here, we performed a comprehensive analysis of the expression heterogeneity and co-expression patterns of trophoblast cell-surface antigen 2 (TROP2), delta-like ligand 3 (DLL3), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) in CRPC samples from a rapid autopsy cohort. We show that DLL3 and CEACAM5 exhibit the highest expression in neuroendocrine prostate cancer (NEPC), while TROP2 is expressed across different CRPC molecular subtypes, except for NEPC. We further demonstrated that AR alterations were associated with higher expression of PSMA and TROP2. Conversely, PSMA and TROP2 expression was lower in RB1-altered tumors. In addition to genomic alterations, we show a tight correlation between epigenetic states, particularly histone H3 lysine 27 methylation (H3K27me3) at the transcriptional start site and gene body of TACSTD2 (encoding TROP2), DLL3, and CEACAM5, and their respective protein expression in CRPC patient-derived xenografts. Collectively, these findings provide insights into patterns and determinants of expression of TROP2, DLL3, and CEACAM5 with implications for the clinical development of cell surface targeting agents in CRPC.
Deficiency of ADAR2 ameliorates metabolic-associated fatty liver disease via AMPK signaling pathways in obese mice
Authors: Kung Mei-Lang , Cheng Siao Muk , Wang Yun-Han , Cheng Kai-Pi , Li Yu-Lin , Hsiao Yi-Tsen , Tan Bertrand Chin-Ming , Chen Yun-Wen
Published: May 2024

Non-alcoholic fatty liver disease (NAFLD) is a chronic disease caused by hepatic steatosis. Adenosine deaminases acting on RNA (ADARs) catalyze adenosine to inosine RNA editing. However, the functional role of ADAR2 in NAFLD is unclear. ADAR2+/+/GluR-BR/R mice (wild type, WT) and ADAR2−/−/GluR-BR/R mice (ADAR2 KO) mice are fed with standard chow or high-fat diet (HFD) for 12 weeks. ADAR2 KO mice exhibit protection against HFD–induced glucose intolerance, insulin resistance, and dyslipidemia. Moreover, ADAR2 KO mice display reduced liver lipid droplets in concert with decreased hepatic TG content, improved hepatic insulin signaling, better pyruvate tolerance, and increased glycogen synthesis. Mechanistically, ADAR2 KO effectively mitigates excessive lipid production via AMPK/Sirt1 pathway. ADAR2 KO inhibits hepatic gluconeogenesis via the AMPK/CREB pathway and promotes glycogen synthesis by activating the AMPK/GSK3β pathway. These results provide evidence that ADAR2 KO protects against NAFLD progression through the activation of AMPK signaling pathways.