bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploration of a European-centered strawberry diversity panel provides markers and candidate genes for the control of fruit quality traits
Authors: Prohaska Alexandre , Rey-Serra Pol , Petit Johann , Petit Aurélie , Perrotte Justine , Rothan Christophe , Denoyes Béatrice 
Published: March 2024

AbstractFruit quality traits are major breeding targets in cultivated strawberry (Fragaria × ananassa). Taking into account the requirements of both growers and consumers when selecting high quality cultivars is a real challenge. Here, we used an original diversity panel enriched with unique European accessions and the 50K FanaSNP array to highlight the evolution of strawberry diversity over the past 160 years, investigate the molecular basis of 12 major fruit quality traits by GWAS, and provide genetic markers for breeding. Results show that considerable improvements of key breeding targets including fruit weight, firmness, composition and appearance occurred simultaneously in European and American populations. Despite the high genetic diversity of our panel, we observed a drop in nucleotide diversity in certain chromosome regions, revealing the impact of selection. GWAS identified 71 associations with 11 quality traits and, while validating known associations (firmness, sugar), highlighted the predominance of new QTL, demonstrating the value of using untapped genetic resources. Three of the six selective sweeps detected are related to glossiness or skin resistance, two little-studied traits important for fruit attractiveness and, potentially, postharvest shelf-life. Moreover, major QTL for firmness, glossiness, skin resistance and susceptibility to bruising are found within a low diversity region of chromosome 3D. Stringent search for candidate genes underlying QTL uncovered strong candidates for fruit color, firmness, sugar and acid composition, glossiness and skin resistance. Overall, our study provides a potential avenue for extending shelf-life without compromising flavor and color as well as the genetic markers needed to achieve this goal.
Local adaptation of a fungal pathogen to temperature along a latitudinal gradient
Authors: Fox Quinn N. , Goodson Carrie , Penczykowski Rachel M. 
Published: March 2024

AbstractWhether climate warming will increase or decrease prevalence of an infectious disease partly depends on the potential for pathogens to adapt to higher temperatures. This potential can be assessed by investigating regional variation in pathogen thermal performance and testing for local adaptation to current temperature regimes and host populations. We collected seeds of a host plant (Plantago rugelii, a perennial herb) and isolated strains of its specialist fungal pathogen (Golovinomyces sordidus, a powdery mildew) from five locations along a latitudinal transect from southern Mississippi to northern Wisconsin, USA. In a laboratory experiment, we placed sympatric and allopatric host–pathogen pairings into seven temperature treatments from 7 to 33 °C. We fitted thermal performance curves to pathogen growth data for each strain. Pathogen strains were locally adapted to temperature, with estimated thermal optima ranging from 20.6 °C (southernmost strain) to 16.7 °C (second-northernmost strain) and generally decreasing 0.26 °C for each degree increase in latitude of origin. However, there was no evidence of pathogen local adaptation to sympatric hosts. Given that powdery mildew spores can disperse long distances via wind, our results suggest that northward spread of warm-adapted strains could facilitate pathogen adaptation to warming climates in this and similar systems.
Tuft cell IL-17RB restrains IL-25 bioavailability and reveals context-dependent ILC2 hypoproliferation
Authors: Feng Xiaogang , Andersson Tilde , Gschwend Julia , Flüchter Pascal , Berest Ivan , Muff Julian L. , Carchidi Daniele , Lechner Antonie , de Tenorio Jeshua C. , Brander Nina , Boehm Ulrich , Klose Christoph S. N. , Artis David , Leinders-Zufall Trese , Zufall Frank , Schneider Christoph 
Published: March 2024

AbstractThe tuft cell–ILC2 circuit orchestrates rapid type 2 responses upon detecting microbe-derived succinate and luminal helminths. Our findings delineate key mechanistic steps, involving IP3R2 engagement and Ca2+flux, governing IL-25 production by tuft cells triggered by succinate detection. While IL-17RB plays a pivotal intrinsic role in ILC2 activation, it exerts a regulatory function in tuft cells. Tuft cells exhibit constitutiveIl25expression, placing them in an anticipatory state that facilitates rapid production of IL-25 protein for ILC2 activation. Tuft cell IL-17RB is crucial for restraining IL-25 bioavailability, preventing excessive tonic ILC2 stimulation due to basalIl25expression. Suboptimal ILC2 stimulation by IL-25 resulting from tuft cellIl17rb-deficiency or prolonged succinate exposure induces a state of hypoproliferation in ILC2s, also observed in chronic helminth infection. Our study offers critical insights into the regulatory dynamics of IL-25 in this circuit, highlighting the delicate tuning required for responses to diverse luminal states.
Identification of regional astrocyte heterogeneity associated with cuprizone-induced de- and remyelination using spatial transcriptomics
Authors: Miedema Anneke , Wijering Marion H.C. , Alsema Astrid M. , Gerrits Emma , Meijer Michel , Koster Mirjam , Wesseling Evelyn M. , Baron Wia , Eggen Bart J.L. , Kooistra Susanne M. 
Published: March 2024

AbstractThe cuprizone model is a well-characterized model to study processes of demyelination and remyelination, which are known features of multiple sclerosis. Cuprizone induces oligodendrocyte loss and severe demyelination in the brain, including the corpus callosum, hippocampus, and cortex. Loss of oligodendrocytes and myelin is accompanied by microgliosis and astrogliosis, wherein microglia and astrocytes partially lose their homeostatic functions and acquire a reactive/activated state. Cuprizone-induced demyelination peaks later in grey matter (GM) than in white matter (WM), and remyelination is more efficient in WM areas. Here, we aim to better understand regional diversity in microglia, astrocytes, and oligodendrocytes and their respective role in remyelination efficiency, by characterizing their response to cuprizone across brain regions. We applied spatial transcriptomics (ST) for unbiased gene activity profiling of multiple brain regions in a single tissue section, to identify region-associated changes in gene activity following cuprizone treatment. Gene activity changes were detected in highly abundant cell types, like neurons, oligodendrocytes, and astrocytes, but challenging to detect in low-abundant cell types such as microglia and oligodendrocyte precursor cells. ST revealed a significant increase in the expression of astrocyte markersClu,Slc1a3,andGfapduring the demyelination phase in the WM fiber tract. In the cortex, the changes in GFAP expression were less prominent, both at the transcriptional and protein level. By mapping genes obtained from scRNAseq of FACS-sorted ACSA2-positive astrocytes onto the ST data, we observed astrocyte heterogeneity beyond the simple classification of WM– and GM-astrocytes in both control and cuprizone-treated mice. In the future, the characterization of these regional astrocyte populations could aid the development of novel strategies to halt the progression of demyelination and support remyelination.Highlights⍰Astrocyte markersClu,Slc1a3,andGfapare increased in WM fiber tracts during demyelination⍰Expression dynamics of astrogliosis markersGfapandVimduring de-and remyelination depend on the brain region⍰Combining scRNAseq with ST data revealed astrocyte heterogeneity beyond WM– and GM-differences⍰scRNAseq-identified gene sets were differently affected by cuprizone treatment across brain regions
Extended Poisson Gaussian-Process Latent Variable Model for Unsupervised Neural Decoding
Authors: Luo Della Daiyi , Giri Bapun , Diba Kamran , Kemere Caleb 
Published: March 2024

AbstractDimension reduction on neural activity paves a way for unsupervised neural decoding by dissociating the measurement of internal neural state repetition from the measurement of external variable tuning. With assumptions only on the smoothness of latent dynamics and of internal tuning curves, the Poisson Gaussian-process latent variable model (P-GPLVM) (Wu et al., 2017) is a powerful tool to discover the low-dimensional latent structure for high-dimensional spike trains. However, when given novel neural data, the original model lacks a method to infer their latent trajectories in the learned latent space, limiting its ability for estimating the internal state repetition. Here, we extend the P-GPLVM to enable the latent variable inference of new data constrained by previously learned smoothness and mapping information. We also describe a principled approach for the constrained latent variable inference for temporally-compressed patterns of activity, such as those found in population burst events (PBEs) during hippocampal sharp-wave ripples, as well as metrics for assessing whether the inferred new latent variables are congruent with a previously learned manifold in the latent space. Applying these approaches to hippocampal ensemble recordings during active maze exploration, we replicate the result that P-GPLVM learns a latent space encoding the animal’s position. We further demonstrate that this latent space can differentiate one maze context from another. By inferring the latent variables of new neural data during running, certain internal neural states are observed to repeat, which is in accordance with the similarity of experiences encoded by its nearby neural trajectories in the training data manifold. Finally, repetition of internal neural states can be estimated for neural activity during PBEs as well, allowing the identification for replay events of versatile behaviors and more general experiences. Thus, our extension of the P-GPLVM framework for unsupervised analysis of neural activity can be used to answer critical questions related to scientific discovery.
Multielectrode array characterization of human induced pluripotent stem cell derived neurons in co-culture with primary human astrocytes
Authors: Lemieux Maddie R. , Freigassner Bernhard , Thathey Zahra , Opp Mark R. , Hoeffer Charles A , Link Christopher D. 
Published: March 2024

AbstractHuman induced pluripotent stem cells (hiPSCs) derived into neurons offer a powerfulin vitromodel to study cellular processes. One method to characterize functional network properties of these cells is using multielectrode arrays (MEAs). MEAs can measure the electrophysiological activity of cellular cultures for extended periods of time without disruption. Here we used WTC11 hiPSCs with a doxycycline-inducible neurogenin 2 (NGN2) transgene differentiated into neurons co-cultured with primary human astrocytes. We achieved a synchrony index ∼0.9 in as little as six-weeks with a mean firing rate of ∼13 Hz. Previous reports show that derived 3D brain organoids can take several months to achieve similar strong network burst synchrony. We also used this co-culture to model aspects of sporadic Alzheimer’s disease by mimicking blood-brain barrier breakdown using a human serum. Our fully human co-culture achieved strong network burst synchrony in a fraction of the time of previous reports, making it an excellent first pass, high-throughput method for studying network properties and neurodegenerative diseases.
Decoding auditory working memory content from EEG aftereffects of auditory-cortical TMS
Authors: Uluç Işıl , Daneshzand Mohammad , Jas Mainak , Kotlarz Parker , Lankinen Kaisu , Fiedler Jennifer L. , Mamashli Fahimeh , Pajankar Netri , Turpin Tori , Navarro de Lara Lucia , Sundaram Padmavathi , Raij Tommi , Nummenmaa Aapo , Ahveninen Jyrki 
Published: March 2024

AbstractWorking memory (WM), short term maintenance of information for goal directed behavior, is essential to human cognition. Identifying the neural mechanisms supporting WM is a focal point of neuroscientific research. One prominent theory hypothesizes that WM content is carried in “activity-silent” brain states involving short-term synaptic changes. Information carried in such brain states could be decodable from content-specific changes in responses to unrelated “impulse stimuli”. Here, we used single-pulse transcranial magnetic stimulation (spTMS) as the impulse stimulus and then decoded content maintained in WM from EEG using multivariate pattern analysis (MVPA) with robust non-parametric permutation testing. The decoding accuracy of WM content significantly enhanced after spTMS was delivered to the posterior superior temporal cortex during WM maintenance. Our results show that WM maintenance involves brain states, which are activity silent relative to other intrinsic processes visible in the EEG signal.
DR5 disulfide bonding as a sensor and effector of protein folding stress
Authors: Law Mary E. , Dulloo Zaafir M. , Eggleston Samantha R. , Takacs Gregory P. , Alexandrow Grace M. , Wang Mengxiong , Su Hanyu , Forsyth Bianca , Chiang Chi-Wu , Sharma Abhisheak , Kanumuri Siva Rama Raju , Guryanova Olga A. , Harrison Jeffrey K. , Tirosh Boaz , Castellano Ronald K. , Law Brian K. 
Published: March 2024

AbstractNew agents are needed that selectively kill cancer cells without harming normal tissues. The TRAIL ligand and its receptors, DR5 and DR4, exhibit cancer-selective toxicity, but TRAIL analogs or agonistic antibodies targeting these receptors have not received FDA approval for cancer therapy. Small molecules for activating DR5 or DR4 independently of protein ligands may bypass some of the pharmacological limitations of these protein drugs. Previously described Disulfide bond Disrupting Agents (DDAs) activate DR5 by altering its disulfide bonding through inhibition of the Protein Disulfide Isomerases (PDIs) ERp44, AGR2, and PDIA1. Work presented here extends these findings by showing that disruption of single DR5 disulfide bonds causes high-level DR5 expression, disulfide-mediated clustering, and activation of Caspase 8-Caspase 3 mediated pro-apoptotic signaling. Recognition of the extracellular domain of DR5 by various antibodies is strongly influenced by the pattern of DR5 disulfide bonding, which has important implications for the use of agonistic DR5 antibodies for cancer therapy. Disulfide-defective DR5 mutants do not activate the ER stress response or stimulate autophagy, indicating that these DDA-mediated responses are separable from DR5 activation and pro-apoptotic signaling. Importantly, other ER stressors, including Thapsigargin and Tunicamycin also alter DR5 disulfide bonding in various cancer cell lines and in some instances, DR5 mis-disulfide bonding is potentiated by overriding the Integrated Stress Response (ISR) with inhibitors of the PERK kinase or the ISR inhibitor ISRIB. These observations indicate that the pattern of DR5 disulfide bonding functions as a sensor of ER stress and serves as an effector of proteotoxic stress by driving extrinsic apoptosis independently of extracellular ligands.
DenoiseST: A dual-channel unsupervised deep learning-based denoising method to identify spatial domains and functionally variable genes in spatial transcriptomics
Authors: Cui Yaxuan , Wang Ruheng , Zeng Xin , Cui Yang , Zhu Zheyong , Nakai Kenta , Ye Xiucai , Sakurai Tetsuya , Wei Leyi 
Published: March 2024

AbstractSpatial transcriptomics provides a unique opportunity for understanding cellular organization and function in a spatial context. However, spatial transcriptome exists the problem of dropout noise, exposing a major challenge for accurate downstream data analysis. Here, we proposed DenoiseST, a dual-channel unsupervised adaptive deep learning-based denoising method for data imputing, clustering, and identifying functionally variable genes in spatial transcriptomics. To leverage spatial information and gene expression profiles, we proposed a dual-channel joint learning strategy with graph convolutional networks to sufficiently explore both linear and nonlinear representation embeddings in an unsupervised manner, enhancing the discriminative information learning ability from the global perspectives of data distributions. In particular, DenoiseST enables the adaptively fitting of different gene distributions to the clustered domains and employs tissue-level spatial information to accurately identify functionally variable genes with different spatial resolutions, revealing their enrichment in corresponding gene pathways. Extensive validations on a total of 18 real spatial transcriptome datasets show that DenoiseST obtains excellent performance and results on brain tissue datasets indicate it outperforms the state-of-the-art methods when handling artificial dropout noise with a remarkable margin of ∼15%, demonstrating its effectiveness and robustness. Case study results demonstrate that when applied to identify biological structural regions on human breast cancer spatial transcriptomic datasets, DenoiseST successfully detected biologically significant immune-related structural regions, which are subsequently validated through Gene Ontology (GO), cell-cell communication, and survival analysis. In conclusion, we expect that DenoiseST is a novel and efficient method for spatial transcriptome analysis, offering unique insights into spatial organization and function.
FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling
Authors: Khan Md Shahjalal H. , Kim Sora Q. , Ross Robert C. , Corpodean Florina , Spann Redin A. , Albarado Diana A. , Fernandez-Kim Sun O. , Clarke Blaise , Berthoud Hans-Rudolf , Münzberg Heike , McDougal David H. , He Yanlin , Yu Sangho , Albaugh Vance L. , Soto Paul , Morrison Christopher D. 
Published: March 2024

AbstractDietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences. In an operant task, protein-restricted male mice responded more for liquid protein rewards, but not carbohydrate, fat, or sweet rewards compared to non-restricted mice. The protein restriction-induced increase in operant responding for protein was absent inFgf21-KO mice and mice with neuron-specific deletion of the FGF21 co-receptor beta-Klotho (KlbCam2ka) mice. Fiber photometry recording of VTA dopamine neurons revealed that oral delivery of maltodextrin triggered a larger activation as compared to casein in control-fed mice, whereas casein triggered a larger activation in protein-restricted mice. This restriction-induced shift in nutrient-specific VTA dopamine signaling was lost inFgf21-KO mice. These data strongly suggest that the increased FGF21 during protein restriction acts in the brain to induce a protein-specific appetite by specifically enhancing the reward value of protein-containing foods and the motivation to consume them.
Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins
Authors: Nieto-Felipe Joel , Macias-Díaz Alvaro , Jimenez-Velarde Vanesa , Lopez Jose J. , Salido Gines M. , Smani Tarik , Jardin Isaac , Rosado Juan A. 
Published: March 2024

AbstractStore-operated Ca2+entry (SOCE) is a mechanism controlled by the filling state of the intracellular Ca2+stores, predominantly the endoplasmic reticulum (ER), where ER-resident proteins STIM1 and STIM2 orchestrate the activation of Orai channels in the plasma membrane, and Orai1 playing a predominant role. Two forms of Orai1, Orai1α and Orai1β, have been identified, which arises the question whether they are equally regulated by STIM proteins. We demonstrate that STIM1 preferentially activates Orai1α over STIM2, yet both STIM proteins similarly activate Orai1β. Under resting conditions, there is a pronounced association between STIM2 and Orai1α, implying their significance in maintaining basal Ca2+levels within the cytosol and ER. STIM1 and STIM2 are also shown to influence the protein levels of the Orai1 variants, independent of Ca2+influx, via lysosomal degradation. Interestingly, Orai1α and Orai1β appear to selectively regulate the protein level of STIM1, but not STIM2. These observations offer crucial insights into the regulatory dynamics between STIM proteins and Orai1 variants, enhancing our understanding of the intricate processes that fine-tune intracellular Ca2+signaling.
Technical and biological variations in the purification of extrachromosomal circular DNA (eccDNA) and the finding of more eccDNA in the plasma of lung adenocarcinoma patients compared with healthy donors
Authors: Zole Egija , Hansen Lasse Bøllehuus , Haskó János , Gerovska Daniela , Araúzo-Bravo Marcos J. , Noer Julie Boertmann , Luo Yonglun , Johansen Jakob Sidenius , Regenberg Birgitte 
Published: March 2024

AbstractHuman plasma DNA originates from all tissues and organs, holding the potential as a versatile marker for diseases such as cancer, as fragments of cancer-specific alleles can be found circulating in the blood. While linear DNA has been studied intensely as a liquid biomarker, the role of circular circulating DNA in cancer is more unknown due, in part, to a lack of comprehensive testing methods. Our developed method profiles extrachromosomal circular DNA (eccDNA) in plasma, integrating Solid-Phase Reversible Immobilization (SPRI) bead purification, the removal of linear DNA and mitochondrial DNA, and DNA sequencing. As an initial assessment, we examined the method, biological variations, and technical variations using plasma samples from four patients with lung adenocarcinoma and four healthy and physically fit individuals. Despite the small sample group, we observed a significant eccDNA increase in cancer patients in two independent laboratories and that eccDNA covered up to 0.4 % of the genome/mL plasma. We found a subset of eccDNA from recurrent genes present in cancer samples but not in every control. In conclusion, our data reflect the large variation found in eccDNA sequence content and show that the variability observed among replicates in eccDNA stems from a biological source and can cause inconclusive findings for biomarkers. This suggests the need to explore other biological markers, such as epigenetic features on eccDNA.