bluuebunny/crossref_metadata_2025_split huggingface dataset:
Peptipedia v2.0: A peptide sequence database and user-friendly web platform. A major update
Authors: Cabas-Mora Gabriel , Daza Anamaría , Soto-García Nicole , Garrido Valentina , Alvarez Diego , Navarrete Marcelo , Sarmiento-Varón Lindybeth , Sepúlveda Yañez Julieta H. , Davari Mehdi D. , Cadet Frederic , Olivera-Nappa Álvaro , Uribe-Paredes Roberto , Medina-Ortiz David 
Published: July 2024

AbstractIn recent years, peptides have gained significant relevance due to their therapeutic properties. The surge in peptide production and synthesis has generated vast amounts of data, enabling the creation of comprehensive databases and information repositories. Advances in sequencing techniques and artificial intelligence have further accelerated the design of tailor-made peptides. However, leveraging these techniques requires versatile and continuously updated storage systems, along with tools that facilitate peptide research and the implementation of machine learning for predictive systems. This work introduces Peptipedia v2.0, one of the most comprehensive public repositories of peptides, supporting biotechnological research by simplifying peptide study and annotation. Peptipedia v2.0 has expanded its collection by over 45% with peptide sequences that have reported biological activities. The functional biological activity tree has been revised and enhanced, incorporating new categories such as cosmetic and dermatological activities, molecular binding, and anti-ageing properties. Utilizing protein language models and machine learning, more than 90 binary classification models have been trained, validated, and incorporated into Peptipedia v2.0. These models exhibit average sensitivities and specificities of 0.877 ± 0.0530 and 0.873 ±0.054, respectively, facilitating the annotation of more than 3.6 million peptide sequences with unknown biological activities, also registered in Peptipedia v2.0. Additionally, Peptipedia v2.0 introduces description tools based on structural and ontological properties and user-friendly machinelearning tools to facilitate the application of machine-learning strategies to study peptide sequences. Peptipedia v2.0 is accessible under the Creative Commons CC BY-NC-ND 4.0 license athttps://peptipedia.cl/.
Systematic evaluation of blastoid models of early human development
Authors: Kim Hani Jieun , Salehin Nazmus , Huang Hao , Zhang Xinran , Jothi Raja , Yang Pengyi 
Published: July 2024

SummaryRecent generation of stem cell-derived blastoids that recapitulate the architecture and cellular constitution of the human blastocyst offers an experimental model for the elucidation of the biology of early human development. To evaluate the fidelity of the blastoids for modelling human blastocysts, we first established a reference map of cell identity and lineage differentiation of the human blastocysts through the integration and curation of single-cell transcriptome data ofex vivoblastocysts profiled at a range of developmental timepoints in culture. We next use this reference map to assess the coverage and the authenticity of cell lineages and the progression of lineage differentiation of various blastoid models generated with different cellular sources and protocols. This reference map generated from this study enables the benchmarking of blastoids that may guide the optimization of the protocol for the generation of high-fidelity blastoid models that faithfully recapitulate the natural human blastocyst.
Substrate specificity and protein stability drive the divergence of plant-specific DNA methyltransferases
Authors: Jiang Jianjun , Gwee Jia , Fang Jian , Leichter Sarah M. , Sanders Dean , Ji Xinrui , Song Jikui , Zhong Xuehua 
Published: July 2024

AbstractDNA methylation is an important epigenetic mechanism essential for transposon silencing and genome integrity. Across evolution, the substrates of DNA methylation have diversified between kingdoms to account for genome complexity. In plants, Chromomethylase3 (CMT3) and CMT2 are the major methyltransferases mediating CHG and CHH methylation, respectively. However, how these two enzymes diverge on substrate specificities during evolution remains unknown. Here, we reveal that CMT2 originates from a duplication of the evolutionarily more ancient CMT3 in flowering plants. Lacking a key arginine residue recognizing CHG in CMT2 impairs its CHG methylation activity in most flowering plants. An engineered V1200R mutation empowers CMT2 to restore both CHG and CHH methylation inArabidopsis cmt2cmt3mutant, testifying a loss-of-function effect for CMT2 after ∼200 million years of evolution. Interestingly, CMT2 has evolved a long and unstructured N-terminus critical for balancing protein stability, especially under heat stress. Furthermore, CMT2 N-terminus is plastic and can be tolerant to various natural mutations. Together, this study reveals the mechanism of chromomethylase divergence for context-specific DNA methylation in plants and sheds important lights on DNA methylation evolution and function.
YTHDF2 upregulation and relocation dictate CD8 T cell polyfunctionality in tumor immunity
Authors: Zhang Haiyan , Luo Xiaojing , Yang Wei , Wu Zhiying , Zhao Zhicong , Pei Xin , Zhang Xue , Chen Chonghao , Lei Josh Haipeng , Shi Qingxia , Zhao Qi , Chen Yanxing , Wu Wenwei , Zeng Zhaolei , Ju Huai-Qiang , Qiu Miaozhen , Liu Jun , Shen Bin , Chen Minshan , Chen Jianjun , Deng Chu-Xia , Xu Rui-Hua , Hou Jiajie 
Published: July 2024

AbstractEpigenetic traits impact the antitumor function of CD8 T cells, yet whether and how RNA methylation programs engage in T cell immunity is poorly understood. Here we show that theN6-methyladenosine (m6A) RNA reader YTHDF2 is highly expressed in early effector or effector-like CD8 T cells and is partially distributed in the nucleus. YTHDF2 loss in T cells exacerbates tumor progression and confers unresponsiveness to PD-1 blockade in mice and humans. In addition to initiating RNA decay for mitochondrial fitness, YTHDF2 can orchestrate chromatin regulation to promote T cell polyfunctionality. YTHDF2-mediatd preservation of gene transcription arises from the interaction of YTHDF2 with IKZF1/3. Accordingly, immunotherapy-induced efficacy could be largely restored in YTHDF2-deficient T cells through combinational use of lenalidomide. Moreover, m6A recognition is fundamental for YTHDF2 translocation to the nucleus and autoregulation at the RNA level. Thus, YTHDF2 coordinates epitranscriptional and transcriptional networks to potentiate T cell immunity.HighlightsYTHDF2 expression and distribution underpin the threshold for bona fide CD8 T cell effector responseCanonical YTHDF2-mRNA decay pathway alleviates mitochondrial stress and CD8 T cell exhaustionNuclear YTHDF2 sequesters IKZF1/3-mediated transcriptional repression to safeguard CD8 T cell polyfunctionalityThe tumoricidal activity of YTHDF2-deficient CD8 T cells could be repaired through the synergy of anti-PD-1 and lenalidomide
Female sex hormones exacerbate retinal neurodegeneration
Authors: Rowe Ashley A. , Reyes Sofia , Velasquez Mauricio J. , Yee Tiffany , Nettesheim Emily R. , McDonald Jeffrey G. , Wert Katherine J. 
Published: July 2024

AbstractNeurodegenerative disorders such as Alzheimer’s disease and macular degeneration represent major sources of human suffering, yet the factors influencing disease severity remain poorly understood. Sex has been implicated as one potential modifying factor. Here, we show that female sex is a risk factor for worsened outcomes in a model of retinal degeneration. Further, we show that this susceptibility is caused by the presence of female-specific circulating sex hormones. The adverse effect of female sex hormones was specific to diseased retinal neurons, and depletion of these hormones ameliorated this phenotypic effect. These findings provide novel insights into the pathogenesis of neurogenerative diseases and how sex hormones can impact the severity of disease. These findings have far-reaching implications for clinical trial design and the use of hormonal therapy in females with certain neurogenerative disorders.
Carbon Dots and Single-walled Carbon Nanotubes Enhances Maize Shading Stress Tolerance
Authors: Khan Mohammad Nauman , Ali Waqar , Grillo Renato , Wu Honghong , Nie Lixiao 
Published: July 2024

AbstractLow sunlight availability/shading stress is one of the major abiotic stresses, limiting plant photosynthesis and biomass production. Maize is a C4 species and requires more sunshine for efficient photosynthesis rate. Thus, maize is a highly shade-sensitive species. We used carbon dots (CDs) and single-walled carbon nanotubes (SWCNTs) as a foliar application to enhance maize photosynthesis under no-shading and shading stress. The results revealed that under shading stress, the higher concentration of CDs and SWCNTs reduced the MDA (Malondialdehyde) content and increased the expression level of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) genes. Moreover, under shading stress, CDs and SWCNTs increased the average thickness of leaf lamina, vascular bundle, mesophyll, and epidermis. CDs and SWCNTs reduced the damaging effects of shading stress on the chloroplast (Ch) formation. CDs and SWCNTs upregulated Rubisco and related genes under shading stress. The chlorophyll fluorescence parameters, including the efficiency of quantum yield of photosystem II (Fv/Fm), electron transport rate (ETR), non-photochemical quenching coefficient (NPQ), and photochemical quenching coefficient (qP) were improved with the foliar application of CDs and SWCNTs under shading stress. Higher stomatal conductance, intercellular CO2concentration, transpiration, and net photosynthesis were observed in maize plants treated with CDs and SWCNTs under shading stress. The results of our study suggest that using higher concentrations of CDs and SWCNTs can enhance plant growth and photosynthesis under shading stress conditions. However, to avoid nanotoxicity, great care is recommended when selecting different concentrations of nanomaterials based on the growing conditions.
The Calmodulin-like proteins, CML13 and CML14 Function as Myosin Light Chains for the Class XI Myosins inArabidopsis
Authors: Symonds Kyle , Duff Liam , Dwivedi Vikas , Belausov Eduard , Pal Lalita , Tominaga Motoki , Haraguchi Takeshi , Sadot Einat , Ito Kohji , Snedden Wayne A 
Published: July 2024

AbstractMyosins are a crucial motor protein associated with the actin cytoskeleton in eukaryotic cells. Structurally, myosins form heteromeric complexes, with smaller light chains such as calmodulin (CaM) bound to isoleucine–glutamine (IQ) domains in the neck region. These interactions facilitate mechano-enzymatic activity. Recently, we identified Arabidopsis CaM-like (CML) proteins CML13 and CML14 as interactors with proteins containing multiple IQ domains, that function as the myosin VIII light chains. This study demonstrates that CaM, CML13, and CML14 specifically bind to the neck region of all 13 Arabidopsis myosin XI isoforms, with some preference among the CaM/CML-IQ domains. Additionally, we observed distinct residue preferences within the IQ domains for CML13, CML14, and CaM.In vitroexperiments revealed that recombinant CaM, CML13, and CML14 exhibit calcium-independent binding to the IQ domains of myosin XIs. Furthermore, when co-expressed with MAP65-1–myosin fusion proteins containing the IQ domains of myosin XIs, CaM, CML13, and CML14 co-localize to microtubules.In vitroactin motility assays demonstrated that recombinant CML13, CML14, and CaM function as myosin XI light chains. Acml13T-DNA mutant exhibited a shortened primary root phenotype that was complemented by the wild-type CML13 and was similar to that observed in a triple myosin XI mutant (xi3KO). Overall, our data indicate that Arabidopsis CML13 and CML14 are novel myosin XI light chains that likely participate in a breadth of myosin XI functions.HighlightMyosin XI proteins play a crucial role in the plant cytoskeleton, but their associated light chains have remained unidentified. Here, we show that calmodulin-like proteins, CML13 and CML14, serve as light chains for myosin XI, similar to their role for myosin VIII proteins
CryoSamba: self-supervised deep volumetric denoising for cryo-electron tomography data
Authors: Costa-Filho Jose Inacio , Theveny Liam , de Sautu Marilina , Kirchhausen Tom 
Published: July 2024

ABSTRACTCryogenic electron tomography (cryo-ET) has rapidly advanced as a high-resolution imaging tool for visualizing subcellular structures in 3D with molecular detail. Direct image inspection remains challenging due to inherent low signal-to-noise ratios (SNR). We introduce CryoSamba, a self-supervised deep learning-based model designed for denoising cryo-ET images. CryoSamba enhances single consecutive 2D planes in tomograms by averaging motion-compensated nearby planes through deep learning interpolation, effectively mimicking increased exposure. This approach amplifies coherent signals and reduces high-frequency noise, substantially improving tomogram contrast and SNR. CryoSamba operates on 3D volumes without needing pre-recorded images, synthetic data, labels or annotations, noise models, or paired volumes. CryoSamba suppresses high-frequency information less aggressively than do existing cryo-ET denoising methods, while retaining real information, as shown both by visual inspection and by Fourier shell correlation analysis of icosahedrally symmetric virus particles. Thus, CryoSamba enhances the analytical pipeline for direct 3D tomogram visual interpretation.
The flow state is not accompanied by frontal-midline theta activity: An EEG investigation of more than 700 video gameplay sessions
Authors: Sugino Hirotaka , Ideriha Takuya , Yamazaki Ryoichiro , Ushiyama Junichi 
Published: July 2024

AbstractPeople sometimes experience a “flow state”—characterized by hyperfocus, time distortion, and loss of self-awareness—during sports or video gameplay. Previous neuropsychological studies using simple laboratory tasks have reported that the flow state is associated with activation in the frontal lobe, reflected in theta (4–7 Hz) band rhythmic neural activity in medial prefrontal regions (frontal-midline theta [FMT] activity). However, the findings of previous studies might be problematic because they did not appropriately capture the neural activity associated with the flow state for the following reasons: 1) they used unfamiliar and unmotivating tasks; 2) they defined the neural basis of the flow state as neural activity occurring during tasks of optimal difficulty, disregarding trial-to-trial variations in subjective experience of the flow state; 3) the duration of the experiment or the number of trials was not sufficient to capture the rare experience of flow; or 4) they ignored individual differences in neural activities related to flow experiences. Thus, we examined the relationship between the flow state and FMT activity, recorded via scalp electroencephalography, in an experimental paradigm that addressed these four issues. First, participants played their favorite competitive video games, which they had been routinely playing. Second, task difficulty was kept as uniform as possible across trials by employing rank matching to directly examine the correlation between subjective flow level and FMT activity across trials. Third, to address the concern regarding the low frequency of the flow experience, more than 100 trials were completed over 10 days by each participant. Lastly, we adopted a within-participant statistical approach to examine individual differences in the nature of the flow experience. The results showed no correlation between FMT activity and the degree of subjective flow in six out of seven participants, contrary to previous reports. Our results challenge the conventional view that frontal lobe activity, as reflected in FMT activity, is instrumental in entering into the flow state.
Specialization into Host Sea Anemones Impacted Clownfish Demographic Responses to Pleistocene Sea Level Changes
Authors: García Jiménez Alberto , Gaboriau Théo , Fitzgerald Lucy M. , Heim Sara , Marcionetti Anna , Schmid Sarah , Bertrand Joris , Litsios Glenn , Shaughnessy Abigail , Santiago Carl , Rangseethampanya Ploypallin , Ruttanachuchote Phurinat , Aunkhongthong Wiphawan , Pengsakun Sittiporn , Sutthacheep Makamas , Frédérich Bruno , Cortesi Fabio , Yemin Thamasak , Salamin Nicolas 
Published: July 2024

AbstractFluctuating sea levels during the Pleistocene led to habitat loss and fragmentation, impacting the evolutionary trajectories of reef fishes. Species with specialized ecological requirements or habitat preferences, like clownfishes (Amphiprioninae), may have been particularly vulnerable due to their intricate dependence on sea anemones. The diverse host specializations within this group likely contributed distinct responses to sea-level fluctuations, differentially shaping their recent evolutionary histories. Leveraging a comprehensive genomic dataset, we reveal demographic patterns and connectivity dynamics across multiple populations of ten clownfish species under different host specializations. Host-generalist species demonstrated strong resilience to habitat perturbations, while those specialized on single hosts suffered dramatic bottlenecks linked to sea-level fluctuations. Spatial analyses revealed the significant role of oceanic currents in shaping clownfish genetic diversity landscapes. Dispersal barriers were driven by environmental variables, with the Coral Triangle emerging as a hub of genetic diversity. Our results reveal how clownfish associative behavior influences their population dynamics, holding major implications for their conservation such as the need to consider their mutualism with sea anemones, particularly on host-specialists, to ensure their survival in the face of climate threats. These findings extend broader principles of conservation, improving our understanding of species’ responses to ecological constraints and environmental changes over evolutionary timescales.
Cell-type specific binocular interactions in mouse visual thalamus
Authors: Masterson Sean P. , Govindaiah Govin , Guido William , Bickford Martha E. 
Published: July 2024

SummaryProjections from each eye are segregated in separate domains within the dorsal lateral geniculate nucleus (dLGN). Yet,in vivostudies indicate that the activity of single dLGN neurons can be influenced by visual stimuli presented to either eye. In this study we explored whether intrinsic circuits mediate binocular interactions in the mouse dLGN. We employed dual color optogeneticsin vitroto selectively activate input from each eye and recorded synaptic responses in thalamocortical (relay) cells as well as inhibitory interneurons, which have extensive dendritic arbors that are not confined to eye specific domains. While most relay cells received monocular retinal input, most interneurons received binocular retinal input; consequently, the majority of dLGN relay cells received binocular retinogeniculate-evoked inhibition. Moreover, in recordings from adjacent pairs of relay cells and interneurons, the most common relationship observed was binocular excitation of interneurons paired with binocular inhibition of adjacent relay cells. Finally, we found that dLGN interneurons are interconnected, displaying both monocular and binocular inhibition in response to retinal activation. In sum, our results indicate that geniculate interneurons provide one of the first locations where signals from the two eyes can be compared, integrated, and adjusted before being transmitted to cortex, shedding new light on the role of the thalamus in binocular vision.HighlightsIn vitro dual color optogenetics examined convergence of eye-specific retinal inputs to thalamocortical (relay) cells and interneurons in the dLGNThe majority of relay cells receive monocular excitatory retinogeniculate input while the majority of interneurons receive binocular inputBinocular relay cells are located in and around the ipsilateral patch whereas binocular interneurons are distributed throughout the dLGNThe majority of relay cells receive binocular retinogeniculate-evoked inhibitiondLGN interneurons are interconnected, receiving both monocular and binocular retinogeniculate-evoked inhibition
The progression of neurovascular features and chemokine signatures of the intervertebral disc with degeneration
Authors: Walk Remy E. , Broz Kaitlyn S. , Jing Liufang , Potter Ryan P. , Gonzalez Christian E. , Beeve Alec T. , Scheller Erica L. , Gupta Munish C. , Setton Lori A. , Tang Simon Y. 
Published: July 2024

AbstractInflammatory cytokine production and de novo neurovascularization have been identified in painful, degenerated intervertebral discs (IVDs). However, the temporal trajectories of these key pathoanatomical features, including the cascade of inflammatory chemokines and neo-vessel and neurite infiltration, and their associations with IVD degeneration, remain relatively unknown. Investigating this process in the caudal mouse IVD enables the opportunity to study the tissue-specific response without confounding inflammatory signaling from neighboring structures. Thus this study aims to define the progression of chemokine production and neurovascular invasion during the IVD degeneration initiated by injury in the caudal spine 3-month-old C57BL6/J mice. Forty-nine IVD-secreted chemokines and matrix metalloproteinases (MMPs) was measured using multiplex ELISA, and the intradiscal infiltrating vessels (endomucin) and nerves (protein-gene-product 9.5) was quantified in the tissue volume using immunohistochemistry. Injury provoked the increase secretion of IL6, CCL2, CCL12, CCL17, CCL20, CCL21, CCL22, CXCL2 and MMP2 proteins. The centrality and structure of inflammatory networks in IVDs evolved over the 12 post-injury weeks, highlighting distinct responses between the acute and chronic phases. Neurites propagated rapidly within 2-weeks post-injury and remained relatively constant until 12-weeks. Vascular vessel length was observed to peak at 4-weeks post-injury and it regressed by 12-weeks. These findings identified the temporal flux of inflammatory chemokines and pain-associated pathoanatomy in a model of IVD degeneration using the mouse caudal spine.