bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellpose as a reliable method for single-cell segmentation of autofluorescence microscopy images
Authors: Riendeau Jeremiah M , Gillette Amani A , Guzman Emmanuel Contreras , Cruz Mario Costa , Kralovec Aleksander , Udgata Shirsa , Schmitz Alexa , Deming Dustin A , Cimini Beth A , Skala Melissa C 
Published: June 2024

AbstractAutofluorescence microscopy uses intrinsic sources of molecular contrast to provide cellular-level information without extrinsic labels. However, traditional cell segmentation tools are often optimized for high signal-to-noise ratio (SNR) images, such as fluorescently labeled cells, and unsurprisingly perform poorly on low SNR autofluorescence images. Therefore, new cell segmentation tools are needed for autofluorescence microscopy. Cellpose is a deep learning network that is generalizable across diverse cell microscopy images and automatically segments single cells to improve throughput and reduce inter-human biases. This study aims to validate Cellpose for autofluorescence imaging, specifically from multiphoton intensity images of NAD(P)H. Manually segmented nuclear masks of NAD(P)H images were used to train new Cellpose models. These models were applied to PANC-1 cells treated with metabolic inhibitors and patient-derived cancer organoids (across 9 patients) treated with chemotherapies. These datasets include co-registered fluorescence lifetime imaging microscopy (FLIM) of NAD(P)H and FAD, so fluorescence decay parameters and the optical redox ratio (ORR) were compared between masks generated by the new Cellpose model and manual segmentation. The Dice score between repeated manually segmented masks was significantly lower than that of repeated Cellpose masks (p<0.0001) indicating greater reproducibility between Cellpose masks. There was also a high correlation (R2>0.9) between Cellpose and manually segmented masks for the ORR, mean NAD(P)H lifetime, and mean FAD lifetime across 2D and 3D cell culture treatment conditions. Masks generated from Cellpose and manual segmentation also maintain similar means, variances, and effect sizes between treatments for the ORR and FLIM parameters. Overall, Cellpose provides a fast, reliable, reproducible, and accurate method to segment single cells in autofluorescence microscopy images such that functional changes in cells are accurately captured in both 2D and 3D culture.
Disorders in lipid metabolism, oxidative stress, and antioxidants in patients with amnestic mild cognitive impairment without major depression
Authors: Nantachai Gallayaporn , Maes Michael , Tran-Chi Vinh-Long , Amrapala Arisara , Vasupanrajit Asara , Hemrungrojn Solaphat , Tunvirachaisakul Chavit 
Published: June 2024

AbstractBackgroundAmnestic mild cognitive impairment (aMCI) is characterized by changes in lipids and oxidative stress (OS). It is crucial to exclude patients with major depression (MDD) to accurately evaluate these biomarkers in aMCI.AimsTo examine lipid and oxidative stress biomarkers associated with aMCI versus normal controls.MethodsWe performed a case-control analysis involving 61 individuals with aMCI (without MDD) and 60 healthy controls. We assessed the severity of aMCI, distress symptoms of old age, and lipid/OS biomarkers.ResultsThe levels of serum -SH groups were significantly higher in individuals with aMCI, while the levels of malondialdehyde (MDA) were significantly lower in the same group. Serum advanced oxidation protein products, glutathione, and folic acid did not show any notable variations. In individuals with aMCI, we observed an elevated apolipoprotein B (ApoB)/ApoA ratio, as well as decreased levels of high-density lipoprotein cholesterol (HDL), ApoA, and a reverse cholesterol transport (RCT) index. The simultaneous presence of aMCI and subclinical depressive symptoms is marked by elevated levels of triglycerides and ApoB, as well as decreased levels of ApoA and HDL. A significant portion of the variability (24.9%) in a quantitative MCI severity score can be attributed to -SH groups, age (positively), MDA and education (inversely).DiscussionThe alterations in MDA and -SH levels in aMCI may potentially disrupt redox signaling, which can affect cell signaling and homeostatic setpoints. The interaction between aMCI and subclinical depressive symptoms can lead to increased atherogenicity and reduced antiatherogenic protection.
Geographic patterns of the number of root canals in permanent molars. A Systematic Review
Authors: Chaple Gil Alain Manuel , Santiesteban Velázquez Meylin , Afrashtehfar Kelvin Ian 
Published: June 2024

ABSTRACTIntroductionThe variability in the distribution and number of root canals in human permanent molars makes endodontic therapy difficult if the prevalence of these patterns is not well known.ObjectiveTo synthesize scientific evidence on geographical variations in the number of root canals in permanent molars.MethodsA study conducted at the University of Medical Sciences of Havana analyzed the number of root canals in permanent molars. We searched for primary studies published in English, Spanish, or Portuguese that reported the number of canals in each tooth. We excluded clinical case studies, editorials, and studies that did not provide specific information on duct anatomy. A sensitivity analysis was performed to assess the impact of the methodological quality of the studies in the two groups. The findings were synthesized by grouping the studies by geographical region and describing the prevalence of different root canal configurations.ResultsData on permanent molars were collected from 93 studies that contributed 60402 molars studied. In Africa, the first and second upper molars commonly have three root canals (45.62% and 41.31%, respectively), similar to the first and second lower molars (59.79% and 67.55%, respectively). In America, the upper first molar most frequently has four root canals (56.66%). In Asia, it is more common to find that all molar groups have three canals (51.09%– 65.58%), except for the lower thirds, which may have two or three canals (42.88% and 57.12%). In Europe, all molars are frequently present with three canals, except for the lower third. In Oceania, the first upper molars commonly have six root canals (65%).ConclusionSignificant variations in the number of root canals in permanent molars according to geographic region were observed. Distinct patterns were observed in the Americas, Asia, Africa, Europe, and Oceania, with varying prevalences of different root canal configurations.
Large-scale generation of uniform sub-100 μm adipocyte spheroids in hydrogel microcapsules using a flow-focusing microfluidic device
Authors: Maekawa Ruri , Hattori Kazuki , Kirisako Hiromi , Iwamoto Yuichiro , Kawasaki Fumiko , Yoneshiro Takeshi , Sakai Juro , Ota Sadao 
Published: June 2024

AbstractAdipocyte spheroids are a promising three-dimensional (3D) cell culture model for obesity research because they reproduce 3D adipose tissue structures and cell-cell interactions better than 2D cultures. However, current methods fail to produce uniformly sized, small adipocyte spheroids at large scales, significantly limiting their use in analysis such as large-scale drug screening. Here, we develop a scalable method that combines simple microfluidics with templated emulsification to generate small, uniformly sized adipocyte spheroids. By encapsulating preadipocytes in numerous hollow agarose microcapsules and incubating them for two days, we reproducibly produced more than 100,000 uniform spheroids with diameters of approximately 50 µm (CV: <13%); we then differentiated preadipocyte spheroids into adipocyte spheroids after an 8-day induction period. Our platform enhances large-scale 3D analysis using adipocyte spheroids for obesity research and can be adapted to generate various spheroid and organoid models, advancing biomedical research across diverse fields.
Identification of genetic modifiers of Huntington’s disease somatic CAG repeat instability by in vivo CRISPR-Cas9 genome editing
Authors: Mouro Pinto Ricardo , Murtha Ryan , Azevedo António , Douglas Cameron , Kovalenko Marina , Ulloa Jessica , Crescenti Steven , Burch Zoe , Oliver Esaria , Vitalo Antonia , Mota-Silva Eduarda , Riggs Marion J. , Correia Kevin , Elezi Emanuela , Demelo Brigitte , Carroll Jeffrey B. , Gillis Tammy , Gusella James F. , MacDonald Marcy E. , Wheeler Vanessa C. 
Published: June 2024

AbstractHuntington’s disease (HD), one of >50 inherited repeat expansion disorders (Depienne and Mandel, 2021), is a dominantly-inherited neurodegenerative disease caused by a CAG expansion inHTT(The Huntington’s Disease Collaborative Research Group, 1993). Inherited CAG repeat length is the primary determinant of age of onset, with human genetic studies underscoring that the property driving disease is the CAG length-dependent propensity of the repeat to further expand in brain (Swamiet al., 2009; GeM-HD, 2015; Hensman Mosset al., 2017; Ciosiet al., 2019; GeM-HD, 2019; Honget al., 2021). Routes to slowing somatic CAG expansion therefore hold great promise for disease-modifying therapies. Several DNA repair genes, notably in the mismatch repair (MMR) pathway, modify somatic expansion in HD mouse models (Wheeler and Dion, 2021). To identify novel modifiers of somatic expansion, we have used CRISPR-Cas9 editing in HD knock-in mice to enablein vivoscreening of expansion-modifier candidates at scale. This has included testing of HD onset modifier genes emerging from human genome-wide association studies (GWAS), as well as interactions between modifier genes, thereby providing new insight into pathways underlying CAG expansion and potential therapeutic targets.
Endothelin B receptor inhibition rescues aging-dependent neuronal regenerative decline
Authors: Feng Rui , Rosen Sarah F. , Ansari Irshad , John Sebastian , Thomsen Michael B. , Geoffroy Cedric G. , Cavalli Valeria 
Published: June 2024

AbstractPeripheral sensory neurons regenerate their axons after injury to regain function, but this ability declines with age. The mechanisms behind this decline are not fully understood. While excessive production of endothelin 1 (ET-1), a potent vasoconstrictor, is linked to many diseases that increase with age, the role of ET-1 and its receptors in axon regeneration is unknown. Using a single cell RNAseq approach, we reveal that in dorsal root ganglia (DRG), satellite glial cells (SGCs), which completely envelop the sensory neuron soma, express the endothelin B receptor (ETBR), while ET-1 is expressed by endothelial cells. Inhibition of ETBRex-vivoin DRG explant cultures improves axon growth in both adult and aged conditions. In vivo,treatment with the FDA- approved compound, Bosentan, improves axon regeneration and reverses the age-dependent decrease in axonal regenerative capacity. Bosentan treatment also enhances the expression of connexin 43 in SGCs after injury in adult and aged mice. These results reveal that inhibiting ETBR function enhances axon regeneration and rescues the age-dependent decrease in axonal regenerative capacity, providing a potential avenue for future therapies.One Sentence SummaryInhibition of endothelin signaling improves nerve regeneration after central and peripheral injuries and counters age-related regenerative decline.
EfficientDe NovoAssembly and Recovery of Microbial Genomes from Complex Metagenomes Using a Reduced Set ofk-mers
Authors: Qayyum Hajra , Ali Amjad , Rehman Kayani Masood Ur 
Published: June 2024

ABSTRACTIn recent years, the analysis of metagenomic data to recover unculturable microbes has revolutionized microbial genomics by rapidly expanding the reference genome catalog. Central to this, are the computational approaches ofde novoassembly and genome binning that enable large-scale reference-independent recovery of microbial genomes from the metagenomic sequencing data. Despite the advancements in bioinformatics approaches to address the computational challenges inherent to these tasks, the limitation of computational resources continues to be a significant barrier to harvesting the full potential of these techniques. Consequently, there is a stressed need to devise strategies involving the fine-tuning of the employed parameters for the effective utilization of the available metagenomic tools. As most of the available metagenome assembly tools are based on thede Bruijngraph framework that relies on a parameterk, selecting an appropriate subset ofk-mers has become a common approach in bioinformatics for efficient computations. In this study, we propose a reduced set ofk-mers, optimized to strike a balance between computational efficiency and the quality of the high- and low-complexity metagenome assemblies. Utilizing this set ofk-mers with MEGAHIT reduces the metagenome assembly time by half compared to the default set, thus greatly reducing the associated computational cost. In addition, it also brings the promise to improve large-scale genome binning studies that adopt this set in the future as we observed an increase in the total number of the recovered genomes as well as obtained higher proportions of high- and medium-quality genomes recovered from the reducedk-mers-based metagenome assemblies.
Broken time reversal symmetry in visual motion detection
Authors: Wu Nathan , Zhou Baohua , Agrochao Margarida , Clark Damon A. 
Published: June 2024

AbstractOur intuition suggests that when a movie is played in reverse, our perception of motion in the reversed movie will be perfectly inverted compared to the original. This intuition is also reflected in many classical theoretical and practical models of motion detection. However, here we demonstrate that this symmetry of motion perception upon time reversal is often broken in real visual systems. In this work, we designed a set of visual stimuli to investigate how stimulus symmetries affect time reversal symmetry breaking in the fruit flyDrosophila’s well-studied optomotor rotation behavior. We discovered a suite of new stimuli with a wide variety of different properties that can lead to broken time reversal symmetries in fly behavioral responses. We then trained neural network models to predict the velocity of scenes with both natural and artificial contrast distributions. Training with naturalistic contrast distributions yielded models that break time reversal symmetry, even when the training data was time reversal symmetric. We show analytically and numerically that the breaking of time reversal symmetry in the model responses can arise from contrast asymmetry in the training data, but can also arise from other features of the contrast distribution. Furthermore, shallower neural network models can exhibit stronger symmetry breaking than deeper ones, suggesting that less flexible neural networks promote some forms of time reversal symmetry breaking. Overall, these results reveal a surprising feature of biological motion detectors and suggest that it could arise from constrained optimization in natural environments.SignificanceIn neuroscience, symmetries can tell us about the computations being performed by a circuit. In vision, for instance, one might expect that when a movie is played backward, one’s motion percepts should all be reversed. Exact perceptual reversal would indicate a time reversal symmetry, but surprisingly, real visual systems break this symmetry. In this research, we designed visual stimuli to probe different symmetries in motion detection and identify features that lead to symmetry breaking in motion percepts. We discovered that symmetry breaking in motion detection depends strongly on both the detector’s architecture and how it is optimized. Interestingly, we find analytically and in simulations that time reversal symmetries are broken in systems optimized to perform with natural inputs.
Cell morphological representations of genes enhance prediction of drug targets
Authors: Iyer Niveditha S. , Michael Daniel J. , Chi S-Y Gordon , Arevalo John , Chandrasekaran Srinivas Niranj , Carpenter Anne E. , Rajpurkar Pranav , Singh Shantanu 
Published: June 2024

AbstractIdentifying how a given chemical of interest exerts its impact on biological systems is a critical step in developing new medicines and chemical products. The mechanism of a query compound of interest can sometimes be identified when its image-based morphological profile matches a compound in a library of well-annotated compound profiles.In this study, we demonstrate a significant improvement in classification performance by incorporating side information: gene representations. We generate these representations using the morphological profiles of cells where the level of a single gene’s expression has been artificially increased or decreased. The genes are selected as those encoding known protein targets of annotated compounds in the library. A transformer model is trained to classify gene-compound pairs, where each pair represents a potential interaction between a gene and a compound, as true or false. Subsequently, the model generates a ranked list of likely target genes for a previously unseen query compound. Although the strategy exhibits high performance only for compounds that target previously encountered genes – likely due to the limited size of our training dataset – the performance increase demonstrates a notable improvement over simply matching compound profiles directly to compound profiles or to gene profiles. Larger datasets may improve the prediction capabilities of this approach, enabling the prediction of gene targets for novel compounds, which can then be experimentally validated.
Patterns and drivers of diatom diversity and abundance in the global ocean
Authors: Pierella Karlusich Juan J. , Cosnier Karen , Zinger Lucie , Henry Nicolas , Nef Charlotte , Bernard Guillaume , Scalco Eleonora , Dvorak Etienne ,   Tara Oceans Coordinators, Jimenez Vieira Fabio Rocha , Delage Erwan , Chaffron Samuel , Ovchinnikov Sergey , Zingone Adriana , Bowler Chris 
Published: June 2024

AbstractDiatoms constitute one of the most diverse and ecologically important phytoplankton groups, yet their large-scale diversity patterns and drivers of abundance are unclear due to limited observations. Here, we utilizeTaraOceans molecular and morphological data, spanning pole to pole, to describe marine diatom diversity, abundance, and environmental adaptation and acclimation strategies. The dominance of diatoms among phytoplankton in terms of relative abundance and diversity was confirmed, and the most prevalent genera wereChaetoceros,Thalassiosira,ActinocyclusandPseudo-nitzschia. We defined 25 distinct diatom communities with varying environmental preferences illustrative of different life strategies. The Arctic Ocean stands out as a diatom hotspot with 6 of the diatom communities being exclusive to it. Light harvesting and photoprotection were among the cellular functions in which natural diatom populations invested the bulk of their transcriptional efforts. This comprehensive study sheds light on marine diatom distributions, offering insights to assess impacts of global change and oceanic anthropogenic impacts.
The long-chain fatty acid-CoA ligase FadD1 monitorsPseudomonas aeruginosaquorum sensing as a receptor of cis-2-decenoic acid
Authors: Song Shihao , Liu Jingyun , Wang Bing , Si Yang , Han Hongguang , Sun Xiuyun , Wang Mingfang , Cui Binbin , Wu Guangliang , Huo Yongliang , Xu Liangxiong , Gao Beile , Yang Liang , Wang Xiaoxue , Zhang Lian-Hui , Deng Yinyue 
Published: June 2024

SUMMARYDiffusible signal factor (DSF)-family quorum sensing (QS) signals are widely utilized by many bacterial pathogens to modulate various biological functions and virulence. Previous studies showed thatcis-2-decenoic acid (cis-DA) is involved in modulation of biofilm dispersion inPseudomonas aeruginosa, but its signaling mechanism remains vague. Here, we report thatcis-DA regulates the physiology and virulence ofP. aeruginosathrough the long-chain fatty acid-CoA ligase FadD1.Cis-DA specifically binds to FadD1 with high affinity and enhances the binding of FadD1 to the promoter DNA region oflasR. Further analysis showed that the FadD1 is a response regulator ofcis-DA with a DNA-binding leucine zipper motif to control the transcription of various target genes. Moreover, FadD1 exhibited catalytic activity oncis-2-dodecenoic acid (BDSF) ofBurkholderia cenocepaciaand enhanced the competitiveness ofP. aeruginosa. Together, our work presents a new DSF-type QS signaling system, which is highlighted by its receptor and response regulator evolved from a canonical enzyme of fatty acid metabolism.Abstract FigureHighlightsThe long-chain fatty acid-CoA ligase FadD1 acts as a global transcriptional regulator inP. aeruginosa. FadD1 is a receptor of QS signalcis-DA and functions at the top of the QS hierarchy inP. aeruginosa. The homolog of FadD1 inP. fluorescenscould bind to the target gene promoter by responding tocis-DA.In briefPseudomonas aeruginosais a human pathogen with antibiotic resistance and a wide range of dynamic defenses makes it an extremely challenging organism to treat in modern-day medicine. It employscis-2-decenoic acid (cis-DA) quorum sensing to regulate the physiology and pathogenesis. Songet al.demonstrate that the long-chain fatty acid-CoA ligase FadD1 controls the important biological functions and virulence inP. aeruginosaas a novel response regulator ofcis-DA signal.
Public Perceptions of Neurotechnologies Used to Target Mood, Memory, and Motor Symptoms
Authors: Furrer Rémy A. , Merner Amanda R. , Stevens Ian , Zuk Peter , Williamson Theresa , Shen Francis X. , Lázaro-Muñoz Gabriel 
Published: June 2024

AbstractBackgroundAdvances in the development of neurotechnologies have the potential to revolutionize treatment of brain-based conditions. However, a critical concern revolves around the willingness of the public to embrace these technologies, especially considering the tumultuous histories of certain neurosurgical interventions. Therefore, examining public attitudes is paramount to uncovering potential barriers to adoption ensuring ethically sound innovation.MethodsIn the present study, we investigate public attitudes towards the use of four neurotechnologies (within-subjects conditions): deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), pills, and MRI-guided focused ultrasound (MRgFUS) as potential treatments to a person experiencing either mood, memory, or motor symptoms (between-subjects conditions). US-based participants (N=1052; stratified to be nationally representative based on sex, race, age) were asked about their perceptions of risk, benefit, invasiveness, acceptability, perceived change to the person, and personal interest in using these neurotechnologies for symptom alleviation.ResultsDescriptive results indicate variability between technologies that the U.S. public is willing to consider if experiencing severe mood, memory, or motor symptoms. The main effect of neurotechnology revealed DBS was viewed as the most invasive and risky treatment and was perceived to lead to the greatest change to who someone is as a person. DBS was also viewed as least likely to be personally used and least acceptable for use by others. When examining the main effects of symptomatology, we found that all forms of neuromodulation were perceived as significantly more beneficial, acceptable, and likely to be used by participants for motor symptoms, followed by memory symptoms, and lastly mood symptoms. Neuromodulation (averaging across neurotechnologies) was perceived as significantly riskier, more invasive, and leading to a greater change to person for mood versus motor symptoms; however, memory and motor symptoms were perceived similarly with respect to risk, invasiveness, and change to person.ConclusionThese results suggest that the public views neuromodulatory approaches that require surgery (i.e., DBS and MRgFUS) as riskier, more invasive, and less acceptable than those that do not. Further, findings suggest individuals may be more reluctant to alter or treat psychological symptoms with neuromodulation compared to physical symptoms.