bluuebunny/crossref_metadata_2025_split huggingface dataset:
ProLLM: Protein Chain-of-Thoughts Enhanced LLM for Protein-Protein Interaction Prediction
Authors: Jin Mingyu , Xue Haochen , Wang Zhenting , Kang Boming , Ye Ruosong , Zhou Kaixiong , Du Mengnan , Zhang Yongfeng 
Published: April 2024

AbstractThe prediction of protein-protein interactions (PPIs) is crucial for understanding biological functions and diseases. Previous machine learning approaches to PPI prediction mainly focus on direct physical interactions, ignoring the broader context of nonphysical connections through intermediate proteins, thus limiting their effectiveness. The emergence of Large Language Models (LLMs) provides a new opportunity for addressing this complex biological challenge. By transforming structured data into natural language prompts, we can map the relationships between proteins into texts. This approach allows LLMs to identify indirect connections between proteins, tracing the path from upstream to downstream. Therefore, we propose a novel frameworkProLLMthat employs an LLM tailored for PPI for the first time. Specifically, we proposeProtein Chain of Thought (ProCoT), which replicates the biological mechanism of signaling pathways as natural language prompts. ProCoT considers a signaling pathway as a protein reasoning process, which starts from upstream proteins and passes through several intermediate proteins to transmit biological signals to downstream proteins. Thus, we can use ProCoT to predict the interaction between upstream proteins and downstream proteins. The training of ProLLM employs the ProCoT format, which enhances the model’s understanding of complex biological problems. In addition to ProCoT, this paper also contributes to the exploration of embedding replacement of protein sites in natural language prompts, and instruction fine-tuning in protein knowledge datasets. We demonstrate the efficacy of ProLLM through rigorous validation against benchmark datasets, showing significant improvement over existing methods in terms of prediction accuracy and generalizability. Our results highlight the potential of LLMs to transform the field of PPI, serving as a robust potential tool for various categories of biological and medical research. The code is available at:https://github.com/MingyuJ666/ProLLM.
Sucrase isomaltase dysfunction influences dietary sucrose intake and preference
Authors: Aldiss Peter , Torices Leire , Ramne Stina , Jørgensen Marit Eika ,   Sucrase-Isomaltase Working Group, D’Amato Mauro , Andersen Mette K 
Published: April 2024

AbstractObjectiveTo characterise the role of Sucrase-isomaltase (SI) in regulating dietary behaviours, such as sweet preference and food liking in Si knockout (Sis-KO) mice and in population-based cohorts from Greenland and the UK.DesignWe profiled the appetitive and post-ingestive response to dietary carbohydrates in SI knockout (Sis-KO) mice. Alongside this, we conducted detailed dietary analysis of 45 foods in two Greenlandic population-based cohorts (IHIT, n=2778 and 68 foods, and B2018, n=2203 and 45 foods) with the presence of a common (allele frequency = 14.3%) SI Loss of function (LoF) variant, c.273-274delAG. Finally, we explored the association between SI hypomorphic variants, liking of 140 foods, and sucrose content using data from 134,766 UKBB participants with exome sequencing and questionnaire data available.ResultsSucrose naïve Sis-KO mice had a significantly reduced intake of dietary sucrose, and preference for 10% liquid sucrose, in two-bottle preference studies. Mechanistically, oral administration of the short-chain fatty acid acetate reduced sucrose-preference in wild-type mice. In Greenlandic LoF homozygous carriers we show that the previously reported reduction in sugar intake may primarily be explained by a lower intake of cake and pastries, and of candy and chocolate and that added sugar is the main factor explaining these associations. In the UKBB, a negative association with “cake icing”, the food with the highest sucrose content per 100g, was detected in SI hypomorphic carriers, as well as in sensitivity analyses conducted only including carriers of known CSID LoF variants. Further, a negative linear relationship was also observed between the effect estimates of hypomorphic SI variants on food liking and the estimated sucrose content per 100g of 88 sucrose-containing foods, indicating that food dislike in SI carriers correlates with the amount of sucrose in food.ConclusionCollectively, we demonstrated that genetic variation in the SI gene is associated with significant changes in sucrose preference, characterised by a rapid avoidance of dietary sucrose in Sis-KO mice, as well as lower consumption and increased disliking of sucrose rich foods in Greenlanders and Europeans, respectively. This work demonstrates that genetic variation in the SI gene may impact physiology beyond the gastrointestinal tract and suggest the possibility to target SI to reduce the preference, and intake, of dietary sucrose with implications for digestive and metabolic health.
Neural correlates of pure presence
Authors: Boly Melanie , Smith Richard , Borrego Giulietta Vigueras , Pozuelos Joan Paul , Alauddin Tariq , Malinowski Peter , Tononi Giulio 
Published: April 2024

AbstractPure presence (PP) is described in several meditative traditions as an experience of a vast, vivid luminosity devoid of perceptual objects, thoughts, and self. Integrated information theory (IIT) predicts that such vivid experiences may occur when the substrate of consciousness in the cerebral cortex is virtually silent. To assess this prediction, we recorded 256-electrode high-density electroencephalography (hdEEG) in long-term meditators of Vajrayana and Zen traditions who were able to reach PP towards the end of a retreat. Because neural activity is typically associated with increased EEG gamma power, we predicted that PP should be characterized by widespread gamma decreases. For meditators of both traditions, PP was associated with decreased broadband hdEEG power compared to within-meditation mind-wandering, most consistent in the gamma range (30–45 Hz). Source reconstruction indicated that gamma decrease was widespread but especially pronounced in posteromedial cortex. PP broadband power also decreased compared to all other control conditions, such as watching or imagining a movie, active thinking, and open-monitoring. PP delta power (1–4Hz) was also markedly decreased compared to dreamless sleep. PP with minimal perceptual contents or accompanied by a feeling of bliss showed hdEEG signatures close to PP. In contrast, gamma activity increased during phases characterized by rich perceptual contents, such as visualization or mantra recitation. Overall, these results are consistent with PP being a state of vivid consciousness during which the cerebral cortex is highly awake (decreased delta activity) but neural activity is broadly reduced (decreased gamma activity), in line with IIT’s predictions.Significance StatementPure presence (PP) is described in several meditative traditions as an experience of a vast, vivid luminosity devoid of perceptual objects, thoughts, and self. Integrated information theory (IIT) predicts that such vivid experiences may occur when the substrate of consciousness in the cerebral cortex is virtually silent. We recorded 256-electrode high-density electroencephalography (hdEEG) in Vajrayana and Zen long-term meditators who could reach PP towards the end of a retreat. Compared to all control conditions, PP was characterized by decreased broadband hdEEG power, most consistent in the gamma range. These results are consistent with PP being a state of vivid consciousness during which the cerebral cortex is highly awake but neural activity is broadly reduced, in line with IIT’s predictions.
Does post-ejaculatory sperm experience prior to fertilization alter offspring performance beyond paternity in an external fertilizing fish?
Authors: Wagle Ranjan , Purchase Craig F. 
Published: April 2024

AbstractRecent research has suggested that the environment encountered by sperm post-ejaculation may impact offspring development beyond the transfer of the paternal genome. The mechanisms that underlie such effects remain unclear, but two non-mutually exclusive processes have been proposed. 1) Haploid selection, whereby stressful conditions act as stronger post-ejaculation pre-fertilization selective pressures on semen than under benign situations, resulting in the fertilization of, on average higher quality sperm and the production of offspring that exhibit superior performance across all environmental conditions that they might encounter. 2) Epigenetic inheritance, where environmental conditions induce changes in sperm that are passed down to offspring, resulting in altered gene expression in offspring. This would be adaptive if sperm experiences anticipate what is to come and improve offspring performance to match those conditions. Capelin (Mallotus villosus) sperm and embryos are sensitive to salinity and may represent a good system to investigate these phenomena. We used a split-ejaculate and split-brood experimental block design to expose capelin sperm to known benign (25 psu) and stressful (35 psu) salinity prior to egg contact, and split each batch of fertilized eggs for incubation at matched and mismatched salinity to those of sperm exposure. Our findings revealed no differences in hatch characteristics between offspring produced by sperm exposed to benign and stressful salinity conditions. A follow-up experiment found the same result with an increased selection gradient at 5 psu and 35 psu. Our study does not support the hypothesis that sperm experiences exert an influence on the development of offspring characteristics, independent of paternity. Instead, our results suggest that the sole influential factor in sperm determining offspring characteristics is the transfer of the paternal genome.
Ade novovariant inPAK2detected in an individual with Knobloch type 2 syndrome
Authors: Werren Elizabeth A. , Kalsner Louisa , Ewald Jessica , Peracchio Michael , King Cameron , Vats Purva , Audano Peter A. , Robinson Peter N. , Adams Mark D. , Kelly Melissa A. , Matson Adam P. 
Published: April 2024

SUMMARYP21-activated kinase 2 (PAK2) is a serine/threonine kinase essential for a variety of cellular processes including signal transduction, cellular survival, proliferation, and migration. A recent report proposed monoallelicPAK2variants cause Knobloch syndrome type 2 (KNO2)—a developmental disorder primarily characterized by ocular anomalies. Here, we identified a novelde novoheterozygous missense variant inPAK2, NM_002577.4:c.1273G>A, p.(D425N), by whole genome sequencing in an individual with features consistent with KNO2. Notable clinical phenotypes include global developmental delay, congenital retinal detachment, mild cerebral ventriculomegaly, hypotonia, FTT, pyloric stenosis, feeding intolerance, patent ductus arteriosus, and mild facial dysmorphism. The p.(D425N) variant lies within the protein kinase domain and is predicted to be functionally damaging byin silicoanalysis. Previous clinical genetic testing did not report this variant due to unknown relevance ofPAK2variants at the time of testing, highlighting the importance of reanalysis. Our findings also substantiate the candidacy ofPAK2variants in KNO2 and expand the KNO2 clinical spectrum.
Cell-TIMP: Cellular Trajectory Inference based on Morphological Parameter
Authors: Raj Piyush , Gupta Himanshu , Anantha Pooja , Barman Ishan 
Published: April 2024

AbstractCellular morphology, shaped by various genetic and environmental influences, is pivotal to studying experimental cell biology, necessitating precise measurement and analysis techniques. Traditional approaches, which rely on geometric metrics derived from stained images, encounter obstacles stemming from both the imaging and analytical domains. Staining processes can disrupt the cell’s natural state and diminish accuracy due to photobleaching, while conventional analysis techniques, which categorize cells based on shape to discern pathophysiological conditions, often fail to capture the continuous and asynchronous nature of biological processes such as cell differentiation, immune responses, and cancer progression. In this work, we propose the use of quantitative phase imaging for morphological assessment due to its label-free nature. For analysis, we repurposed the genomic analysis toolbox to perform trajectory inference analysis purely based on morphology information. We applied the developed framework to study the progression of leukemia and breast cancer metastasis. Our approach revealed a clear pattern of morphological evolution tied to the diseases’ advancement, highlighting the efficacy of our method in identifying functionally significant shape changes where conventional techniques falter. This advancement offers a fresh perspective on analyzing cellular morphology and holds significant potential for the broader research community, enabling a deeper understanding of complex biological dynamics.
A neural compass in the human brain during naturalistic virtual navigation
Authors: Lu Zhengang , Julian Joshua B. , Aguirre Geoffrey K. , Epstein Russell A. 
Published: April 2024

ABSTRACTA central component of wayfinding is the ability to maintain a consistent representation of one’s facing direction when moving about the world. In rodents, head direction cells are believed to support this “neural compass”, but identifying a similar mechanism in humans during dynamic naturalistic navigation has been challenging. To address this issue, we acquired fMRI data while participants freely navigated through a virtual reality city. Encoding model analyses revealed voxel clusters in retrosplenial complex and superior parietal lobule that exhibited reliable tuning as a function of facing direction. Crucially, these directional tunings were consistent across perceptually different versions of the city, spatially separated locations within the city, and motivationally distinct phases of the behavioral task. Analysis of the model weights indicated that these regions may represent facing direction relative to the principal axis of the environment. These findings reveal specific mechanisms in the human brain that allow us to maintain a sense of direction during naturalistic, dynamic navigation.
A rat model of cirrhosis with well-differentiated hepatocellular carcinoma induced by thioacetamide
Authors: Hu Zhiping , Kurihara Takeshi , Sun Yiyue , Cetin Zeliha , Florentino Rodrigo M. , Faccioli Lanuza A. P. , Liu Zhenghao , Yang Bo , Ostrowska Alina , Soto-Gutierrez Alejandro , Delgado Evan R. 
Published: April 2024

ABSTRACTHepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, and commonly associated with hepatic fibrosis or cirrhosis. This study aims to establish a rat model mimicking the progression from liver fibrosis to cirrhosis and subsequently to HCC using thioacetamide (TAA). We utilized male Lewis rats, treating them with intra-peritoneal injections of TAA. These rats received bi-weekly injections of either 200 mg/kg TAA or saline (as a control) over a period of 34 weeks. The development of cirrhosis and hepatocarcinogenesis was monitored through histopathological examinations, biochemical markers, and immunohistochemical analyses. Our results demonstrated that chronic TAA administration induced cirrhosis and well-differentiated HCC, characterized by increased fibrosis, altered liver architecture, and enhanced hepatocyte proliferation. Biochemical analyses revealed significant alterations in liver function markers, including elevated alpha-fetoprotein (AFP) levels, without affecting kidney function or causing significant weight loss or mortality in rats. This TAA-induced cirrhosis and HCC rat model successfully replicates the clinical progression of human HCC, including liver function impairment and early-stage liver cancer characteristics. It presents a valuable tool for future research on the mechanisms of antitumor drugs in tumor initiation and development.
Utility Analyses of AVITI Sequencing Chemistry
Authors: Liu Silvia , Obert Caroline , Yu Yan-Ping , Zhao Junhua , Ren Bao-Guo , Liu Jia-Jun , Wiseman Kelly , Krajacich Benjamin J. , Wang Wenjia , Metcalfe Kyle , Smith Mat , Ben-Yehezkel Tuval , Luo Jian-Hua 
Published: April 2024

AbstractBackgroundDNA sequencing is a critical tool in modern biology. Over the last two decades, it has been revolutionized by the advent of massively parallel sequencing, leading to significant advances in the genome and transcriptome sequencing of various organisms. Nevertheless, challenges with accuracy, lack of competitive options and prohibitive costs associated with high throughput parallel short-read sequencing persist.ResultsHere, we conduct a comparative analysis using matched DNA and RNA short-reads assays between Element Biosciences’ AVITI and Illumina’s NextSeq 550 chemistries. Similar comparisons were evaluated for synthetic long-read sequencing for RNA and targeted single-cell transcripts between the AVITI and Illumina’s NovaSeq 6000. For both DNA and RNA short-read applications, the study found that the AVITI produced significantly higher per sequence quality scores. For PCR-free DNA libraries, we observed an average 89.7% lower experimentally determined error rate when using the AVITI chemistry, compared to the NextSeq 550. For short-read RNA quantification, AVITI platform had an average of 32.5% lower error rate than that for NextSeq 550. With regards to synthetic long-read mRNA and targeted synthetic long read single cell mRNA sequencing, both platforms’ respective chemistries performed comparably in quantification of genes and isoforms. The AVITI displayed a marginally lower error rate for long reads, with fewer chemistry-specific errors and a higher mutation detection rate.ConclusionThese results point to the potential of the AVITI platform as a competitive candidate in high-throughput short read sequencing analyses when juxtaposed with the Illumina NextSeq 550.
Discovery of anti-infective compounds againstMycobacterium marinumafter biotransformation of simple natural stilbene scaffolds by a fungal secretome
Authors: Nitschke Jahn , Huber Robin , Vossio Stefania , Moreau Dimitri , Marcourt Laurence , Gindro Katia , Queiroz Emerson F. , Soldati Thierry , Hanna Nabil 
Published: April 2024

ABSTRACTThis study evaluated the efficacy of a high-throughputDictyostelium discoideum–Mycobacterium marinumDd-Mm infection system by first benchmarking it against a set of antibiotics and second in screening a library of natural product (NP) derivatives for anti-infective activity against intracellularMycobacterium marinum(Mm). The study observed no activity of pyrazinamide against Mm, consistent with known resistance patterns, and confirmed other antibiotics, such as rifampicin and bedaquiline, with activity below defined antibacterial susceptibility breakpoints. From screening a small library of NP derivatives,trans-δ-viniferins emerged as promising anti-infective scaffolds, particularly two compounds which exhibited an anti-infective activity on Mm during infection but not on Mm in broth,17with an IC50of 18.1 µM, and19with an IC50of 9 µM). Subsequent exploration via halogenation and structure-activity relationship (SAR) studies led to the identification of derivatives with improved selectivity and potency. The observed anti-infective phenotype may involve mechanisms such as blocking mycobacterial virulence factors or boosting host defense. Furthermore, the study highlights the potential of natural product-inspired derivatization approaches for drug discovery and underscores the utility of the Dd-Mm infection system in identifying novel anti-infective compounds.IMPORTANCEThis study underscores the significance of leveraging natural product-inspired approaches and innovative infection models in search for novel anti-infective compounds. By benchmarking and employing high-throughputDictyostelium discoideum-Mycobacterium marinuminfection system on a small, focused library of natural product derivatives, the study identifiedtrans-δ-viniferins as promising anti-infective scaffolds againstMycobacterium marinum, opening potential therapeutic avenues for combating tuberculosis. The findings highlight the value of exploring nature-inspired chemistry for drug discovery and addressing global health challenges.
Droplet Hi-C for Fast and Scalable Profiling of Chromatin Architecture in Single Cells
Authors: Chang Lei , Xie Yang , Taylor Brett , Wang Zhaoning , Sun Jiachen , Tan Tuyet R. , Bejar Rafael , Chen Clark C. , Furnari Frank B. , Hu Ming , Ren Bing 
Published: April 2024

AbstractComprehensive analysis of chromatin architecture is crucial for understanding the gene regulatory programs during development and in disease pathogenesis, yet current methods often inadequately address the unique challenges presented by analysis of heterogeneous tissue samples. Here, we introduce Droplet Hi-C, which employs a commercial microfluidic device for high-throughput, single-cell chromatin conformation profiling in droplets. Using Droplet Hi-C, we mapped the chromatin architecture at single-cell resolution from the mouse cortex and analyzed gene regulatory programs in major cortical cell types. Additionally, we used this technique to detect copy number variation (CNV), structural variations (SVs) and extrachromosomal DNA (ecDNA) in cancer cells, revealing clonal dynamics and other oncogenic events during treatment. We further refined this technique to allow for joint profiling of chromatin architecture and transcriptome in single cells, facilitating a more comprehensive exploration of the links between chromatin architecture and gene expression in both normal tissues and tumors. Thus, Droplet Hi-C not only addresses critical gaps in chromatin analysis of heterogeneous tissues but also emerges as a versatile tool enhancing our understanding of gene regulation in health and disease.
NuCDB: A databank of nucleic acids circular dichroism spectra
Authors: Das Uttam , Magateshvaren Saras Murali Aadhitya , Rathinavelan Thenmalarchelvi 
Published: April 2024

AbstractNucleic acids take a variety of secondary structures depending on the sequence and environmental conditions. Circular dichroism (CD) spectroscopy quickly provides the secondary structural information of nucleic acids.Nucleic acidCircular-dichroismDataBank (NuCDB)https://project.iith.ac.in/nucdb/, a repository of nucleic acid secondary structure CD spectra published during 1964-2012, is created. Besides acting as the repository for the nucleic acids CD spectra,NuCDBalso has the facility to upload recently published CD spectra to keep the repository up-to-date. This repository provides the sequence-structure-environmental relationship of different nucleic acid fragments in one platform. Until today, CD is used for studying the secondary structure of smaller nucleic acid fragments. Since different parts of the genome and transcriptome of an organism have combinations of various secondary structures and play a crucial role in regulating the biological processes, the CD spectra of longer nucleic acid sequences would be more realistic. Thus, this bioinformatics repository would be helpful in training machine learning models to predict the presence of multiple secondary structures in a given CD spectra.