bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of a harmful algal bloom (Karenia selliformis) on the benthic invertebrate community and the sea otter (Enhydra lutris) diet in eastern Hokkaido
Authors: Johnstone Jackson , Suzuki Ippei , Konno Natsuki , Murayama Kyohei , Ochiai Satsuki , Davis Randall , Mitani Yoko 
Published: April 2024

AbstractIn recent decades, the locally extinct sea otter (Enhydra lutris lutris) has been recolonizing the coast of eastern Hokkaido. Their diet includes benthic invertebrates such as bivalves, sea urchins, snails, and chitons. In the fall of 2021, a harmful algal bloom (HAB) ofKarenia selliformisoccurred across Hokkaido’s northern and eastern coasts, leading to a massive mortality of sea urchins. This dinoflagellate produces a neurotoxin (gymnodimine) implicated in shellfish poisoning. To determine the effect of the HAB on the marine community, we conducted benthic surveys using SCUBA and visually monitored the prey items of the sea otters in the affected area from 2020 to 2023. Following the HAB, we observed an 82% decrease in benthic sea urchin density (number m2), leading to their complete absence from the diet of sea otters. Conversely, bivalve density increased six-fold, accompanied by a nearly two-fold rise in their percentage in the sea otters’ diet. Minimal changes were observed in the density of chitons and snails, with no significant alteration in the sea otters’ diet. Despite these changes, the impact of the HAB on otters’ dietary preferences was temporary, as the percentage of dietary sea urchins began recovering one year later. Sea otters augmented their diet with bivalves to compensate for the reduced availability of sea urchins during the HAB with no apparent effects on the number of sea otters or their health. Our results highlight the adaptability of sea otters to adjust their diet according to prey availability.
Single-cell allelic transcriptomic analysis unravels intratumoral gene expression heterogeneity linked to TNBC pathogenesis
Authors: Ayyamperumal Parichitran , Naik Hemant Chandru , Naskar Amlan Jyoti , Gayen Srimonta 
Published: April 2024

AbstractTriple-negative breast cancer (TNBC) is the most aggressive subclass of breast cancer, which exhibits high intratumoral heterogeneity. Intratumoral heterogeneity often drives the evolution of drug resistance towards tumour therapy in TNBC. However, the contributing factors and mechanisms behind the intratumoral heterogeneity in TNBC remain poorly understood. It has been implicated that copy number variations (CNVs) often create allelic imbalance and thereby contribute to intratumoral gene expression heterogeneity. However, other processes, such as epigenetic and transcriptional processes, can also contribute to allelic expression heterogeneity in tumour cells. Here, we have investigated how allelic expression heterogeneity contributes to intratumoral heterogeneity in TNBC by performing genome-wide allelic gene expression analysis, excluding most of the CNVs, using single-cell RNA-sequencing datasets. We found widespread monoallelic expression of many genes across different cell types of TNBC. Notably, we found a profound heterogeneity of allelic expression patterns of many genes within TNBC epithelial cells, creating distinct subpopulations of epithelial cells. Importantly, we show that these genes with allelic expression pattern heterogeneity between subpopulations are linked to TNBC immune-surveillance and drug-resistance related pathways, thereby overall shaping the pathogenesis outcomes. Finally, we show that the promoter regions of these genes with profound monoallelic expression are often hypermethylated in TNBC patients. Altogether, our findings reveal that heterogeneous allelic expression patterns contribute to intratumoral heterogeneity and are linked to TNBC pathogenesis.
Three pollen QTLs are sufficient to partially break stylar unilateral incompatibility ofSolanum pennellii
Authors: Ma Wenchun , Li Yumei , He Mingxia , Baldwin Ian T. , Guo Han 
Published: April 2024

Summary●In tomato clade, bothself-incompatibility(S-) locus-dependent and –independent mechanisms are present in unilateral incompatibility (UI). Several stylar UI factors mediatingS-locus-independent mechanism have been gradually uncovered, however, related pollen UI (pui) factors still await more studies.●Quantitative trait loci (QTL) mapping, comparative transcriptomics and introgression lines (ILs) /inbred backcross lines (BILs)-based functional analysis were applied for identification and functional validation ofpuiQTLs between self-compatible (SC)Solanum lycopersicumand SCS. pennelliiLA0716.●In addition to the reportedpui10.1(SpFPS2), twopuiQTLs (pui6.2andpui12.1) were identified. Pollen tubes of cultivated tomatoes introgressed with threepuiloci could partially break the stylar UI response in LA0716 styles. Furthermore, a conserved function ofpui12.1was found in the styles of SCS.habrochaitesLA0407 and SCS.chmielewskiiLA1028. Three candidate genes linked topui6.2andpui12.1were screened for further analysis.●This study reveals a potential synergistic relationship of the threepuiQTLs in breaking stylar UI response of LA0716 and will advance our understanding of the genetic mechanisms underlying UI in the tomato clade.HighlightOur data revealed that breaking the stylar unilateral incompatibility ofSolanum pennelliiLA0716 requires not only the reported pollen UI (pui) factor but also another twopuiQTLs identified in this study.
Structural basis for molecular assembly of fucoxanthin chlorophylla/c-binding proteins in a diatom photosystem I supercomplex
Authors: Kato Koji , Nakajima Yoshiki , Xing Jian , Kumazawa Minoru , Ogawa Haruya , Shen Jian-Ren , Ifuku Kentaro , Nagao Ryo 
Published: April 2024

AbstractPhotosynthetic organisms exhibit remarkable diversity in their light-harvesting complexes (LHCs). LHCs are associated with photosystem I (PSI), forming a PSI-LHCI supercomplex. The number of LHCI subunits, along with their protein sequences and pigment compositions, has been found to differ greatly among the PSI-LHCI structures. However, the mechanisms by which LHCIs recognize their specific binding sites within the PSI core remain unclear. In this study, we determined the cryo-electron microscopy structure of a PSI supercomplex incorporating fucoxanthin chlorophylla/c-binding proteins (FCPs), designated as PSI-FCPI, isolated from the diatomThalassiosira pseudonanaCCMP1335. Structural analysis of PSI-FCPI revealed five FCPI subunits associated with a PSI monomer; these subunits were identified as RedCAP, Lhcr3, Lhcq10, Lhcf10, and Lhcq8. Through structural and sequence analyses, we identified specific protein-protein interactions at the interfaces between FCPI and PSI subunits, as well as among FCPI subunits themselves. Comparative structural analyses of PSI-FCPI supercomplexes, combined with phylogenetic analysis of FCPs fromT. pseudonanaand the diatomChaetoceros gracilis, underscore the evolutionary conservation of protein motifs crucial for the selective binding of individual FCPI subunits. These findings provide significant insights into the molecular mechanisms underlying the assembly and selective binding of FCPIs in diatoms.
Exploring differences between depression and bipolar disorder through the urinary proteome
Authors: Liu Yuqing , Li Zhiyu , Dong Yeqing , Yang Jian , Li Meijuan , Zhou Jingjing , Gao Ying , Li Jie , Wang Gang , Gao Youhe 
Published: April 2024

AbstractHow to differentiate the diagnosis of depression and bipolar disorder has always been an important problem that needs to be solved urgently in clinical practice. In this study, from the perspective of urine proteomics, urine samples of similar age were collected from two hospitals to investigate the candidate biomarkers for differentiating the diagnosis of depression and bipolar disorder using both group analysis and one-to-many analysis(1 patient: many control samples). The experimental results of the paired group analysis showed that 108 differential proteins were identified in the depressed group compared to the bipolar group under strict screening conditions with screening criteria of FC ≥ 2 or ≤ 0.5 and a two-tailed unpaired t-test of P < 0.01, with an average of 3.7 randomly generated differential proteins, and a confidence level of 96.6 % for the correlation between these proteins and the disease difference. In the one-to-many analysis, 24 differential proteins were co-identified by the samples of 13 depressed patients, 16 of which showed a completely consistent trend of expression changes in all depressed patients studied, and 6 of which were associated with immunoglobulins; 41 differential proteins were co-identified by the samples of 12 depressed patients out of 13, and 19 of which showed a completely consistent trend of expression change in the These results reflect the strong consistency of differential proteins between the two groups of patients. 12 or more samples from depressed patients were enriched for differential proteins related to multiple biological processes and signaling pathways associated with the immune system, which is consistent with previous studies: immune mechanisms may be one of the pathogenetic mechanisms of major depression and that drugs with major immune targets can improve depressive symptoms. In the future, it may be possible to observe the immune status of patients with depression to provide direction and basis for the precise treatment of depression. The results of this paper show that urine proteomics can differentiate between depression and bipolar disorder, suggest possible mechanisms and potential targets for the treatment of depression and bipolar disorder, and provide a tool for future differential diagnosis and precision treatment of the diseases.
Efficient coding in biophysically realistic excitatory-inhibitory spiking networks
Authors: Koren Veronika , Malerba Simone Blanco , Schwalger Tilo , Panzeri Stefano 
Published: April 2024

AbstractThe principle of efficient coding posits that sensory cortical networks are designed to encode maximal sensory information with minimal metabolic cost. Despite the major influence of efficient coding in neuroscience, it has remained unclear whether fundamental empirical properties of neural network activity can be explained solely based on this normative principle. Here, we derive the structural, coding, and biophysical properties of excitatory-inhibitory recurrent networks of spiking neurons that emerge directly from imposing that the network minimizes an instantaneous loss function and a time-averaged performance measure enacting efficient coding. We assumed that the network encodes a number of independent stimulus features varying with a time scale equal to the membrane time constant of excitatory and inhibitory neurons. The optimal network has biologically-plausible biophysical features, including realistic integrate-and-fire spiking dynamics, spike-triggered adaptation, and a non-specific excitatory external input. The excitatory-inhibitory recurrent connectivity between neurons with similar stimulus tuning implements feature-specific competition, similar to that recently found in visual cortex. Networks with unstructured connectivity cannot reach comparable levels of coding efficiency. The optimal ratio of excitatory vs inhibitory neurons and the ratio of mean inhibitory-to-inhibitory vs excitatory-to-inhibitory connectivity are comparable to those of cortical sensory networks. The efficient network solution exhibits an instantaneous balance between excitation and inhibition. The network can perform efficient coding even when external stimuli vary over multiple time scales. Together, these results suggest that key properties of biological neural networks may be accounted for by efficient coding.
A latent variable model for evaluating mutual exclusivity and co-occurrence between driver mutations in cancer
Authors: Shuaibi Ahmed , Chitra Uthsav , Raphael Benjamin J. 
Published: April 2024

AbstractA key challenge in cancer genomics is understanding the functional relationships and dependencies between combinations of somatic mutations that drive cancer development. Suchdrivermutations frequently exhibit patterns ofmutual exclusivityorco-occurrenceacross tumors, and many methods have been developed to identify such dependency patterns from bulk DNA sequencing data of a cohort of patients. However, while mutual exclusivity and co-occurrence are described as properties of driver mutations, existing methods do not explicitly disentangle functional, driver mutations from neutral,passengermutations. In particular, nearly all existing methods evaluate mutual exclusivity or co-occurrence at the gene level, marking a gene as mutated if any mutation – driver or passenger – is present. Since some genes have a large number of passenger mutations, existing methods either restrict their analyses to a small subset of suspected driver genes – limiting their ability to identify novel dependencies – or make spurious inferences of mutual exclusivity and co-occurrence involving genes with many passenger mutations. We introduce DIALECT, an algorithm to identify dependencies between pairs ofdrivermutations from somatic mutation counts. We derive a latent variable mixture model for drivers and passengers that combines existing probabilistic models of passenger mutation rates with a latent variable describing the unknown status of a mutation as a driver or passenger. We use an expectation maximization (EM) algorithm to estimate the parameters of our model, including the rates of mutually exclusivity and co-occurrence between drivers. We demonstrate that DIALECT more accurately infers mutual exclusivity and co-occurrence between driver mutations compared to existing methods on both simulated mutation data and somatic mutation data from 5 cancer types in The Cancer Genome Atlas (TCGA).
Alterations in Gut Archaea Composition and Their Bacterial Interactions Linked to Hypertension
Authors: Yuan Wen , Chen Yihang , Liang Lirong , Fan Luyun , Chi Hongjie , Wang Xiucheng , Li Jing , Zhang Xun , Feng Lin , Dong Ying , Su Pixiong , Zhong Jiuchang , Cai Jun , Liu Xiaoyan 
Published: April 2024

AbstractAlterations in the gut microbiota have been linked to hypertension, with the role of archaea, despite being stable constituents, remaining largely unexplored. Shotgun metagenomic analyses of fecal samples were performed on 341 participants from 3 cohorts: discovery cohort (88 individuals), validation cohort 1 (175 individuals), and validation cohort 2 (78 individuals). Principal Coordinates Analysis (PCoA) based on Bray-Curtis distances revealed significant alterations in the composition of enteric archaea between control individuals and hypertensive patients (P < 0.05). Hypertensive groups showed reduced abundances of halophilic archaea (Halorhabdus, Halovivax, and Halorubrum_lipolyticum) and methanogenic archaea (Methanomassiliicoccus and Candidatus_Methanomassiliicoccus_intestinalis). Eleven archaea species, depleted in fecal samples from hypertensive patients, distinguished them from control individuals, with areas under the receiver operating characteristic curve of 0.85, 0.79, and 0.91 in the discovery, validation cohort 1, and validation cohort 2, respectively. Significant correlations were observed between these archaea and clinical data across cohorts. Additionally, a significant positive correlation in richness between gut bacteria and archaea suggests a close cross-kingdom synergy within the microbiome. This study highlights significant shifts in the archaeal populations of hypertensive patients, underscoring the potential of archaeal biomarkers in hypertension diagnosis and suggesting avenues for future therapeutic research.
Secondhand tobacco exposure assessed using urinary cotinine among 10 years children in Japan: A 11-years repeated cross-sectional study
Authors: Tamada Yudai , Takeuchi Kenji , Tabuchi Takahiro 
Published: April 2024

AbstractIntroductionThe emergence of heated tobacco products (HTPs) has complicated the issue of secondhand tobacco (SHT) exposure. We investigated the trend in SHT exposure in schoolchildren and assessed whether SHT exposure depends on household tobacco use status.MethodsThis repeated cross-sectional study from 2011 to 2021 (15,927 subjects were eligible) was based on data from an annual survey of fourth-grade students (aged 10 years) in Kumagaya City, located in Kanto Region, Japan. Data were collected by questionnaire, and urinary cotinine levels used as an objective indicator of SHT exposure, such as secondhand exposure to combustible cigarette (CC) smoke and HTP-generated aerosols.ResultsSHT exposure has decreased by about one-quarter over the 11-year period, from 18.6% in 2011 to 5.3% in 2021. Regarding household tobacco product use, 68.1% did not use tobacco products, 16.5% were CC-only users, 12.3% were HTP-only users, and 3.0% were both CC and HTP users. The prevalence of SHT exposure among participants was significantly higher compared to participants with no tobacco product users in the household, in the following order: both CC and HTP users, only CC users, and only HTP user.ConclusionsWhile the prevalence of SHT exposure showed a decreasing trend during 2011-2021, the prevalence of SHT exposure was higher in schoolchildren from families with tobacco product users than in schoolchildren from families without tobacco product users, regardless of the type of tobacco product.
Neural networks representing temporal expectation in mice
Authors: Wendlandt T. Adrian , Wenk Patricia , Henschke Julia U. , Michalek Annika , Noesselt Toemme , Pakan Janelle M.P. , Budinger Eike 
Published: April 2024

AbstractThe ability to attend to specific moments in time is crucial for survival across species facilitating perception and motor performance by leveraging prior temporal knowledge for predictive processing. Despite its importance, the neural mechanisms underlying the utilization of macro-scale and meso-scale neural resources during temporal processing and their relationship to behavioural strategies and motor responses remain largely unexplored. To investigate the capacity for predictive temporal structure of multisensory stimuli to optimize motor behaviour, we established a behavioural paradigm, in which mice were trained to an auditory-cue and visual-target presented at expected or unexpected temporal delays. Using a combination of stimulus-evoked and resting-state functional magnetic resonance imaging, we examined task-related evoked activity in brain-wide networks and found that that the formation of temporal expectations relying on accumulated sensory information and combined multisensory input involves plasticity across large macro-scale cortical networks comprised of primary sensory systems, sensory association areas including posterior parietal cortex, retrosplenial cortex, prefrontal top-down executive control centres of the brain, as well as hippocampal networks. Additionally, employing in vivo two-photon calcium imaging, we explored local single-cell dynamics within the posterior parietal cortex during this task and found that temporal expectation could be decoded directly from neuronal activity within this brain region. Overall, our study provides insights into the neural correlates underlying the formation of multisensory temporal expectations in the mouse brain and highlights the recruitment of neural resources across temporally-driven statistical learning processes.
CRISPR-GPT: An LLM Agent for Automated Design of Gene-Editing Experiments
Authors: Qu Yuanhao , Huang Kaixuan , Cousins Henry , Johnson William A. , Yin Di , Shah Mihir , Zhou Denny , Altman Russ , Wang Mengdi , Cong Le 
Published: April 2024

AbstractThe introduction of genome engineering technology has transformed biomedical research, making it possible to make precise changes to genetic information. However, creating an efficient gene-editing system requires a deep understanding of CRISPR technology, and the complex experimental systems under investigation. While Large Language Models (LLMs) have shown promise in various tasks, they often lack specific knowledge and struggle to accurately solve biological design problems. In this work, we introduce CRISPR-GPT, an LLM agent augmented with domain knowledge and external tools to automate and enhance the design process of CRISPR-based gene-editing experiments. CRISPR-GPT leverages the reasoning ability of LLMs to facilitate the process of selecting CRISPR systems, designing guide RNAs, recommending cellular delivery methods, drafting protocols, and designing validation experiments to confirm editing outcomes. We showcase the potential of CRISPR-GPT for assisting non-expert researchers with gene-editing experiments from scratch and validate the agent’s effectiveness in a real-world use case. Furthermore, we explore the ethical and regulatory considerations associated with automated gene-editing design, highlighting the need for responsible and transparent use of these tools. Our work aims to bridge the gap between biological researchers across various fields with CRISPR genome engineering technology and demonstrate the potential of LLM agents in facilitating complex biological discovery tasks.
Discovery and characterization of unusual O-link glycosylation of IgG4 antibody using LC-MS
Authors: Janecki Dariusz J. , Kao-Scharf Chi-Ya , Hoffmann Andreas 
Published: April 2024

4ABSTRACTThe analysis of several batches of commercial biopharmaceutical product Dupixent using top-down intact mass spectrometry revealed that this immunoglobulin IgG4 features a small amount of O-link glycosylation in Fab region. This is the first report of an O-link glycosylation in IgG4 antibody. The paper describes most likely structure of the O-link glycosylation as well as probable location(s). The relative quantification showed only small quantity of the modification but appearing consistently in several batches of Dupixent. The O-link glycosylation site was characterized by standard tryptic peptide digestion and LC-MS analysis approach.
Estrogen Receptor α/14-3-3 molecular glues as alternative treatment strategy for endocrine resistant breast cancer
Authors: Visser Emira J. , Collier Maria Donaldson , Siefert Joseph C. , Konstantinidou Markella , Paul Susana N. , Berkhout Jari B. , Virta Johanna M. , Somsen Bente A. , Cossar Peter , Miley Galen , Luzietti Lara , Young Leonie , Vareslija Damir , Buluwela Lakjaya , Ali Simak , Meijer Onno C. , Arkin Michelle R. , Ottmann Christian , Zwart Wilbert , Brunsveld Luc 
Published: April 2024

SummaryEndocrine resistance in breast cancer treatment is a major clinical hurdle, causing an urgent need for alternative treatment modalities. The suppressive protein-protein interaction (PPI) between Estrogen Receptor alpha (ERα) and the adaptor protein 14-3-3 offers such a strategy. Here, we report the biological impact of small-molecule ‘molecular glues’ of this ERα/14-3-3 PPI by using both fusicoccin-derived semi-synthetic natural products and fully synthetic covalent drug-like molecules. We show that the ERα/14-3-3 PPI is stabilized by both the natural- and synthetic glues, resulting in a suppression of ERα transcriptional activity and a blockade of breast cancer cell proliferation, both in cell lines and in organoids derived from endocrine therapy resistant breast cancer patients. Importantly, the molecular glues effectively blocked ERα action even in case of constitutively active clinical ERα mutations, providing the foundations for developing alternative classes of ERα targeting compounds to improve treatment of patients with endocrine-therapy resistant breast cancer.Abstract Figure