bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Three Dimensional Immunolabeling Method with Peroxidase-fused Nanobodies and Fluorochromized Tyramide-Glucose Oxidase Signal Amplification
Authors: Yamauchi Kenta , Koike Masato , Hioki Hiroyuki 
Published: October 2024

AbstractThree dimensional immunohistochemistry (3D-IHC), immunolabeling of 3D tissues, reveals the spatial organization of molecular and cellular assemblies in the context of the tissue architecture. Deep and rapid penetration of antibodies into 3D tissues and highly sensitive detection are critical for high-throughput imaging analysis of immunolabeled 3D tissues. Here, we report a nanobody (nAb)-based 3D-IHC, POD-nAb/FT-GO 3D-IHC, for high-speed and high-sensitive detection of targets within 3D tissues. Peroxidase-fused nAbs (POD-nAbs) enhanced immunolabeling depth and allowed for highly sensitive detection by combined with a fluorescent tyramide signal amplification system, Fluorochromized Tyramide-Glucose Oxidase (FT-GO). Multiplex labeling was implemented to the 3D-IHC by quenching POD with sodium azide. Using the 3D-IHC technique, we successfully visualized somata and processes of neuronal and glial cells in millimeter-thick mouse brain tissues within three days. Given its high-speed and high-sensitive detection, our 3D-IHC protocol, POD-nAb/FT-GO 3D-IHC, would provide a useful platform for histochemical analysis in 3D tissues.
Social Experience Shapes Fighting Strategies for Reproductive Success
Authors: Gao Can , Ma Mingze , Chen Jie , Ji Xiaoxiao , Peng Qionglin , Pan Yufeng 
Published: October 2024

AbstractSocial isolation generally increases aggression but decreases mating competition, resulting in an intricate and ambiguous relationship between social experience, aggression, and reproductive success. In maleDrosophila, aggression is often characterized by lunging, a frequent and comparatively gentle combat behavior. Here, we establish a behavioral paradigm for studying a less frequent but more vigorous fighting form known as tussling. We discover that while social enrichment decreases lunging, aligning with past observations, it heightens the more forceful tussling behavior. These two forms of aggression rely on different olfactory receptor neurons, specifically Or67d for lunging and Or47b for tussling. We further identify three pairs of central pC1 neurons that specifically promote tussling. Moreover, shifting from lunging to tussling in socially enriched males facilitates better territory control and mating success, mitigating the disadvantages associated with aging. These findings reveal how social experience shapes fighting strategies to optimize reproductive success.
Understanding the epidemiology and pathogenesis ofMycobacterium tuberculosiswith non-redundant pangenome and population genetics
Authors: Zhou Yang , Anthony Richard , Wang Shengfen , Xia Hui , Ou Xichao , Zhao Bing , Song Yuanyuan , Zheng Yang , He Ping , Liu Dongxin , Zhao Yanlin , van Soolingen Dick 
Published: October 2024

AbstractTuberculosis is a major public health threat demanding more than one million lives every year. Many challenges exist to defeat this deadly infectious disease which address the importance of a thorough understanding of the biology of the causative agentMycobacterium tuberculosis(MTB). We generated a non-redundant pangenome of 420 epidemic MTB strains from China. We estimate that MTB strains have a pangenome of 4,278 genes encoding 4,183 proteins, of which 3,438 of which are core genes. However, due to 99,694 interruptions in 2,447 coding genes, only 1,651 may be translated in all samples, which dramatically reduces the number of active core genes. Of these interruptions, 67,315 (67.52%) could be classified by various genetic variations detected by currently available tools, and more than half of them are due to structure variations, mostly small indels. We further describe differential evolutionary patterns of genes under the influences of selective pressure, population structure and background selection. While selective pressure is ubiquitous among these coding genes, evolutionary adaptations primarily occur in 1,313 genes. Genes located in the cell wall and membrane region are under the strongest selective pressure, while biological processes including regulation of transcription, translation and regulation of growth are under strongest background selection in MTB. The metabolism of fatty acids may be an outstanding example of evolutionary adaption for MTB under current selective pressure. This study provides a comprehensive view on the genetic diversity and evolution patterns of coding genes in MTB which may deepen our understanding of its epidemiology and pathogenicity.
Dopamine transmission in the anterior insula shapes the neural coding of anxiety
Authors: Couderc Yoni , Reddy Tanmai Dhani , Vardiero Giovanni , Garg Archi , Ricci Daria , d’Almeida Marion , Nicolas Céline , Habchi Tina , Wu Yue K. , Gjorgjieva Julijana , Li Yulong , Valjent Emmanuel , Beyeler Anna 
Published: October 2024

AbstractThe insular cortex (or insula), and particularly its anterior region, plays a crucial role in the control of emotional valence and anxiety (Etkin & Wager, 2007; Méndez-Ruette et al., 2019; Nicolas et al., 2023). While dopamine neurotransmission is known to modulate anxiety levels in humans (Hjorth et al., 2021) and animal models (de la Mora et al., 2010; Bananej et al., 2012; Zarrindast & Khakpai, 2015; DeGroot et al., 2020; Godino et al., 2023), its regulatory effects on the anterior insula remained unexplored. Here, using a multifaceted approach, we uncovered how dopamine shapes anterior insula function in anxiety and valence processing. First, we revealed a high density of neurons expressing type-1 dopamine receptors (D1) in the insula, particularly important in the anterior insula, and seven times greater than the density of neurons expressing type-2 dopamine receptors (D2). Few neurons co-expressedDrd1 and Drd2mRNAs in the anterior and posterior insula, and the density ofDrd1+neurons in the anterior insula was twice higher among inhibitory neurons than excitatory neurons. Second, we found that pharmacological activation of D1 in the anterior insula is anxiogenic, suggesting a direct link between insular dopamine signaling and anxiety-related behaviors. Using fiber-photometry recordings, we identified that the amplitude of dopamine release onto D1+ neurons in the anterior insula while mice were in anxiogenic spaces or receiving mild foot shocks was both positively correlated with mice level of trait anxiety. Population dynamics and deep-learning analyses of anterior insula single-unit recordings uncovered distinct coding patterns of anxiety-provoking and safe environments, as well as tastants of positive and negative valence. Remarkably, systemic D1 activation, which heightens anxiety- related behaviors, dampens this coding dichotomy by increasing coding variability for protected spaces while increasing the coding reliability for anxiogenic spaces. Interestingly, the coding reliability of anxiogenic areas was positively correlated with mice level of trait anxiety, and we observed a trend towards a positive correlation between the coding reliability of a negative tastants, and mice level of anxiety. Altogether, our findings provide a new model of neural population coding of anxiety and emotional valence and unravel D1-dependent coding mechanisms in the mouse anterior insula.
Hydrothermally treated yeast cell wall suppresses the growth of MCF7 cells under isolated conditions
Authors: Kitagawa Takanori 
Published: October 2024

AbstractTraditionally, yeast cell wall (YCW) has limited applications because of their low solubility. To overcome this, a novel method was developed using a hydrothermal reaction to enhance its solubility and decrease its viscosity; this resulted in the production of a soluble form of YCW, known as the YCW treated with hydrothermal reaction (YCW-H), with broader chemical composition. Therefore, in the present study, we aim to investigate YCW-H, a hydrothermally treated YCW product with enhanced solubility, for the inhibition of cancer cell proliferation. YCW-H promotes plant growth by effectively regulating soil microspheres. YCW-H inhibited the growth of MCF-7 breast cancer cells even after complete physical separation from the cells. This suggests the presence of a diffusible cytotoxic factor in YCW-H, a phenomenon not observed in the presence of untreated YCW. Since YCW-H possess reactive carbon species (RCS), we hypothesized that the reactive radical species generated during the hydrothermal treatment of YCW are responsible for this effect. The addition of Fe(III) ions to YCW-H further amplified the production of RCS and its inhibitory activity across the plastic barrier, correlating with the increased RCS levels. The radicals migrated to the water in wells adjacent to YCW-H, indicating that RCS generation is a key determinant of the inhibition of cancer cell growth. Moreover, compounds containing RCS were confirmed to exhibit cytotoxicity. Thus, our findings underscore the RCS-containing compounds from YCW-H as promising candidates for developing novel medical devices for cancer treatment.
Sex Differences in Contextual Extinction Learning After Single Binge-Like EtOH Exposure in Adolescent C57BL/6J Mice
Authors: Cardona-Jordan Kiara M. , Lay-Rivera Xiany X. , Cartagena-López Eliezer , Bracho-Rincón Dina L. , González-Bermejo Ruth , Alvarado-Monefeldt Gerardo L. , Gonzalez Del Toro Jovangelis P. , Esquilín-Rodríguez Christian J. , Lloret-Torres Mario , Velázquez-Marrero Cristina 
Published: October 2024

ABSTRACTThe relationship between chronic heavy drinking and post-traumatic stress disorder (PTSD) is well-documented; however, the impact of more common drinking patterns, such as a single episode leading to a blood alcohol concentration (BAC) of 0.09 g/dL (moderate intoxication), remains underexplored. Given the frequent co-occurrence of PTSD and alcohol misuse, it is essential to understand the biological and behavioral factors driving this comorbidity. We hypothesize that alcohol’s immediate sedative effects are coupled with the development of persistent molecular alcohol tolerance, which may disrupt fear extinction learning. To investigate this, we employed aSingleEpisodeEthanol(SEE)in-vivoexposure to mimic binge-like alcohol consumption over a 6-hour period, following contextual conditioning trials. Extinction trials were conducted 24 hours later to assess the effects on extinction learning. Our findings reveal a significant deficit in fear extinction learning in alcohol-treated adolescent male mice compared to saline-treated controls, with no such effects observed in female adolescent mice. These results suggest that even non-chronic alcohol exposure may contribute to the development of trauma- and stress-related disorders, such as PTSD, in males. Additionally, histological analysis revealed significant alterations in FKBP5, β-catenin, and GSK-3β levels in the hippocampus, striatum, and basolateral amygdala of alcohol-treated mice following extinction. The insights gained from this study could reshape our understanding of the risk factors for PTSD and open new avenues for prevention and treatment, targeting the molecular mechanisms that mediate alcohol tolerance.STATEMENT OF SIGNIFICANCEThis study investigates the impact of binge-like alcohol exposure on context extinction learning, aiming to identify previously unrecognized risks associated with this common drinking pattern and the development of trauma- and stress-related disorders, such as PTSD. Our findings reveal that binge-like alcohol exposure impairs extinction learning in male adolescent mice by disrupting molecular mechanisms within fear memory circuits, suggesting novel therapeutic and preventive targets. Dysregulated candidates include the canonical Wnt/β-catenin signaling proteins, β-catenin and GSK-3β, along with FKBP5, a key player in glucocorticoid signaling and part of a gene network linked to PTSD. These alterations, found in the dorsal hippocampus (dHPC), basolateral amygdala (BLA), striatum, and nucleus accumbens (NAc) core and shell, may serve as promising targets for future pharmacological intervention.
Heavy Metal and Antibiotic Co-resistance in Bacteria Isolated from Poultry Samples in Bangladesh: An Emerging Environmental Threat
Authors: Sarker Amily , Haque Nabila , Ayaz Mohammad , Antu Umme Samia , Mou Taslin Jahan , Dey Shuvra Kanti , Parvez Md.Anowar Khasru 
Published: October 2024

AbstractThe excessive use of heavy metals and antibiotics as additives in livestock feed may significantly contribute to bacterial resistance in poultry environments by exerting selective pressure. This study aimed to comprehensively analyze bacterial isolates from poultry farms across Bangladesh, focusing on their resistance to heavy metals and antibiotics. Through microbial phenotypic screening, 23 cadmium-resistant and 28 chromium-resistant bacterial isolates were identified. The minimum inhibitory concentrations (MICs) for cadmium and chromium in metal-resistant bacterial isolates varied significantly, ranging from 200 μg/ml to 1600 μg/ml. All cadmium-resistant isolates were fully resistant to cefixime and ceftazidime, while chromium-resistant isolates showed 90% resistance to tetracycline. The cadmium resistance gene, such asczc, was detected in 26% (6/23) of cadmium-resistant isolates, and the chromium reductase genechrRwas detected in 18% (5/28) of chromium-resistant isolates. Among the chromium-reductase isolates, 40% (2/5) exhibited co-resistance and harbored thechrRgene, beta-lactam resistance genes (bla-TEM,bla-NDM), and the colistin resistance gene (mcr-2). A significant association (p = 0.026) was observed between the presence of thechrRgene and these antibiotic resistance genes. However, no co-resistance was found in cadmium-resistant isolates. Mobile genetic elements, specifically Class 1 integrons, were found in 33.33% (2/6) of the isolates carrying the cadmium resistance gene (czc) and in 100% (5/5) of the isolates containing the chromium reductase gene (chrR). These findings underscore poultry environments in Bangladesh as significant reservoirs for bacteria with dual resistance to heavy metals and antibiotics, emphasizing the need for further investigation into the genetic mechanisms driving microbial resistance and its implications for public health.
µPIX: Leveraging Generative AI for Enhanced, Personalized and Sustainable Microscopy
Authors: Bon Gabriel , Sapède Daniel , Matthews Cédric , Daian Fabrice 
Published: October 2024

ABSTRACTFluorescence microscopy is a critical tool in bio-cellular research, enabling the visualization of biological tissues and cellular structures. However, the inevitable aging of microscopes can degrade their performance posing challenges for long-term scientific investigations. In this study, we introduceµPIX, a personalized deep learning workflow based on a Generative Adversarial Network (GAN) utilizing a Pix2Pix architecture. The network is trained in a supervised manner to denoise images, optimize pre-processing for binary segmentation, and compensate for equipment aging. Our results, evaluated using standard image quality and binary segmentation metrics, demonstrate thatµPIXoutperforms popular deep learning architectures based on convolutional auto-encoder networks for similar tasks. Additionally, our generative model effectively rejuvenates older detectors to perform on par with newer ones, not only by improving image quality but also by preserving resolution in depth and maintaining a near-linear response between original and generated images in terms of pixel intensity (crucial for quantitative imaging). These findings suggest that generative deep learning approaches can significantly contribute to more sustainable, cost-effective microscopy, fostering continued innovation and discovery in biological research.
Using synthetic RNA to benchmark poly(A) length inference from direct RNA sequencing
Authors: Chang Jessie J-Y , Yang Xuan , Teng Haotian , Reames Benjamin , Corbin Vincent , Coin Lachlan 
Published: October 2024

AbstractPolyadenylation is a dynamic process which is important in cellular physiology. Oxford Nanopore Technologies direct RNA-sequencing provides a strategy for sequencing the full-length RNA molecule and analysis of the transcriptome and epi-transcriptome. There are currently several tools available for poly(A) tail-length estimation, including well-established tools such astailfindrandnanopolish, as well as two more recent deep learning models:DoradoandBoostNano. However, there has been limited benchmarking of the accuracy of these tools against gold-standard datasets. In this paper we evaluate four poly(A) estimation tools using synthetic RNA standards (Sequins), which have known poly(A) tail-lengths and provide a valuable approach to measuring the accuracy of poly(A) tail-length estimation. All four tools generate mean tail-length estimates which lie within 12% of the correct value. Overall,Doradois recommended as the preferred approach due to its relatively fast run times, low coefficient of variation and ease of use with integration with base-calling.
Clinical characteristics, drug-resistance genes and virulence analysis of carbapenem-resistant Klebsiella pneumoniae
Authors: He Junning , Zhang Peilin , Li Cheng , Xie Ning , Yin Yijie , Wang Guixia , Liang Xianting , Liu Yongfang 
Published: October 2024

OBJECTIVEThe aim was to investigate the clinical infection characteristics, risk factors and convergence of carbapenem-resistant and hypervirulent Klebsiella pneumoniae(hv-CRKP) in our hospital, in order to provide scientific basis for the rational use of antibiotics in the clinic.METHODSCRKP strains were isolated from clinical specimens of 44 patients in central intensive care unit (CICU), neurosurgery intensive care unit (NICU) and emergency intensive care unit (EICU) of our hospital in 41 months. The clinical manifestations of the patients were analyzed, and the hypermucoviscous phenotype was defined by string test. The drug resistance gene, virulence gene and capsular specific serotype of the isolated strains were detected by polymerase chain reaction (PCR) technology, and the gene of CRKP producing KPC enzyme was sequence.RESULTSThe incidence of sepsis in 44 patients with CRKP infection was 25.0%, and the overall treatment failure rate was 38.6%. All the 44 strains of CRKP produced KPC enzyme, and all of them were blaKPC-2(100%);14 strains (31.8%) were positive in string test; 23 strains (52.3%) were found to have virulence related genes, including 10 strains (22.7%) of rmpA, 16 strains (36.4%) of iucA and 19 strains (43.2%) of peg-344. 5 strains (11.4%) were capsule-specific serotypes and 13 strains (29.5%) were identified as hv-CRKP.CONCLUSIONThe mechanism of CRKP resistance in our hospital isblaKPC-2, the detection rates of virulence gene, string test positive and hypervirulent capsular specific serotype are all relatively high in CRKP, there are not a few Klebsiella pneumoniae with carbapenem-resistant and hypervirulent.
Dysfunction of the episodic memory network in the Alzheimer’s disease cascade
Authors: Lattmann-Grefe René , Vockert Niklas , Machts Judith , Suksangkharn Yanin , Yakupov Renat , Schütze Hartmut , Glanz Wenzel , Incesoy Enise , Butryn Michaela , Lüsebrink Falk , Schmid Matthias , Stark Melina , Kleineidam Luca , Spottke Annika , Coenjaerts Marie , Brosseron Frederic , Fliessbach Klaus , Schneider Anja , Dechent Peter , Hetzer Stefan , Scheffler Klaus , Ramirez Alfredo , Laske Christoph , Sodenkamp Sebastian , Altenstein Slawek , Schneider Luisa-Sophie , Gref Daria , Spruth Eike Jakob , Lohse Andrea , Schott Björn H. , Wiltfang Jens , Kilimann Ingo , Goerss Doreen , Rostamzadeh Ayda , Priller Josef , Peters Oliver , Hellmann-Regen Julian , Teipel Stefan , Jessen Frank , Maass Anne , Ziegler Gabriel , Düzel Emrah 
Published: October 2024

AbstractAlzheimer’s disease (AD) is a major cause of dementia and cognitive decline. Here we assessed how episodic memory circuit dysfunction, a hallmark of AD, is related to the longitudinal cascade of AD biomarkers, neurodegeneration and cognition using data from the DZNE Longitudinal Cognitive Impairment and Dementia study. This data set is unique by including over 1000 longitudinal functional magnetic resonance imaging (fMRI) measurements during episodic memory encoding. We leveraged a disease progression model (DPM) to obtain AD progression scores. Voxel-wise analyses revealed widespread loss of deactivation (hyperactivation) and activation (hypoactivation) with increasing disease stage. Hyperactivation trajectories were nonlinear and visually preceded trajectories of cognition. Overall, hyperactivation was independently associated with co-occurrence of amyloid- and tau-positivity and neurodegeneration, suggesting synaptic dysfunction and neurodegeneration as two independent drives of cognitive decline. Our results therefore provide evidence for a critical time window in which pharmacological treatments targeting the synapse may improve cognition.
Experimental evolution ofDrosophilawithout its microbiome
Authors: Malwade Akshay , Koner Anish , Vibishan B. , Gadkari Chinmay , Saini Sarthak , Khodake Vinayak , Dey Sutirth 
Published: October 2024

AbstractThe ability of the gut microbiome to contribute to diverse host phenotypes and, in turn, alter host fitness, raises the possibility that the presence of such microbes can influence the host’s evolution. However, empirical studies on the evolutionary aspects of host-microbe relationships are rare. Here, we used experimental evolution on laboratory populations ofD. melanogasterto understand how a host can evolve without its microbiome. For this, we compared replicateDrosophilapopulations reared without the microbes (labeled as MBL1-4, for “Microbiota-less”) for 54 host generations with their corresponding controls (labeled as MB1-4), whose microbiome was reconstituted every generation. This comparison was done in two common-garden assay environments: with microbes and microbe-free. We found that contrary to what we expected, only modest adaptations were seen in the MBL populations. When looking at the phenotypic plasticity of MB-MBLs across with-microbe and microbe-free environments, we saw that MBLs had lesser plasticity than MBs. This might hint at MBLs reducing their dependence on microbes. We performed RNA-Seq on MBL1and MB1populations to see if there were changes in gene expression patterns. We found that a cluster of anti-microbial peptides (AMPs) was up-regulated, and another cluster of heat shock proteins (HSPs) was down-regulated in MBL1compared to MB1. These results show that while the host’s homeostasis is perturbed by microbiome manipulation on short timescales, the host-microbiome integration seems more labile on longer timescales, with hosts showing potential for adaptation without the microbes.