bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of human appetite-regulating neurons and tanycytes from stem cells
Authors: Abay-Nørgaard Zehra , Müller Anika K , Hänninen Erno , Rausch Dylan , Piilgaard Louise , Christensen Jens Bager , Peeters Sofie , Schörling Alrik L. , Salvador Alison , Nikulina Viktoriia , Li Yuan , Kajtez Janko , Pers Tune H , Kirkeby Agnete
Published: July 2024

The balance between energy intake and expenditure is controlled by the hypothalamus, a small brain region characterised by high neuronal diversity. Specifically, the arcuate nucleus (ARC) and ventromedial hypothalamus (VMH) are key hypothalamic nuclei controlling appetite through behavioural response to circulating humoral signals. Yet, despite their physiological importance, the cellular and functional characteristics of this highly specialised neural region has been studied mainly in animals due to a lack of human models. Here, we fine-tuned the differentiation of human pluripotent stem cells toward the ARC and VMH hypothalamic nuclei and identified key subtype-specific progenitor markers of these subregions. We demonstrate that the timing for initiation and termination of bone morphogenetic protein (BMP) signalling is essential for controlling subregional specification of tuberal hypothalamic progenitors along the anterior-posterior axis, balancing VMH versus ARC fates. A particular population of SHH-/NKX2.1+/FGF10high/RAXhigh/TBX3highposterior tuberal progenitors was identified as the source for generation of ARC-associated agouti-related peptide (AGRP) neurons and tanycytes whilst anterior tuberal SHH+/NKX2.1+/FGF10low/RAXlow/TBX3lowprogenitors generated VMH phenotypes including NR5A1 neurons. Upon maturationin vitroand in xenografts, ARC-patterned progenitors gave rise to key appetite-regulating cell types including those producing AGRP, prepronociceptin (PNOC), growth hormone-releasing hormone (GHRH), thyrotropin-releasing hormone (TRH) and pro-opiomelanocortin (POMC), as well as tanycyte glial cells. Differentiated ARC cultures showed high transcriptomic similarity to the human ARC and displayed evidence of functionality by AGRP secretion and responsiveness to leptin and fibroblast growth factor 1 (FGF1). In summary, our work provides insights into the developmental lineages underlying hypothalamic subregional specification and enables access to highly characterised human ARC and VMH cultures, which will provide novel opportunities for investigating the cellular and molecular pathways triggered by obesity-associated genetic variants and weight-regulating stimuli.
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

In 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

Recent 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

DNA 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

Epigenetic 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.

Highlights

YTHDF2 expression and distribution underpin the threshold for bona fide CD8 T cell effector response

Canonical YTHDF2-mRNA decay pathway alleviates mitochondrial stress and CD8 T cell exhaustion

Nuclear YTHDF2 sequesters IKZF1/3-mediated transcriptional repression to safeguard CD8 T cell polyfunctionality

The 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

Neurodegenerative 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

Low 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

Myosins 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.

Highlight

Myosin 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

Cryogenic 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

People 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

Fluctuating 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

Projections 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.

Highlights

In vitro dual color optogenetics examined convergence of eye-specific retinal inputs to thalamocortical (relay) cells and interneurons in the dLGN

The majority of relay cells receive monocular excitatory retinogeniculate input while the majority of interneurons receive binocular input

Binocular relay cells are located in and around the ipsilateral patch whereas binocular interneurons are distributed throughout the dLGN

The majority of relay cells receive binocular retinogeniculate-evoked inhibition

dLGN 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

Inflammatory 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.
Early signs of plant community responses to climate warming along mountain roads in Switzerland
Authors: Iseli Evelin , Zeugin Nathan Diaz , Brioschi Camille , Alexander Jake , Lenoir Jonathan
Published: July 2024

Global warming is pushing species to shift their ranges towards higher latitudes and elevations, causing a reassembly of plant communities potentially accompanied by community thermophilization (i.e., an increasing number or cover of thermophilic species, sometimes at the expense of mesic or cold-adapted species). Given the large variation typically observed in the magnitude and direction of range shifts, quantifying community thermophilization might provide a sensitive method to detect range shifts within short time periods and across limited spatial extents. Assessing changes in plant community composition as a whole might integrate early signs of range shifts across co-occurring species while accounting for changes in both occurrence and abundance.

Here, we combine an assessment of (i) species-level range shifts, (ii) changes in species richness and (iii) changes in community-inferred temperatures along three mountain roads in Switzerland to ask whether plant communities have responded to warming climate over a 10 year period, and whether community thermophilization is an appropriate metric for early detection of these changes.

We found a community thermophilization signal of +0.13°C over the 10-year study period based on presence-absence data only. Despite significant upward shifts of species’ upper range limits in the lower part of the studied elevational gradient and a decrease in species richness at high elevations, significant thermophilization was not detectable if community- inferred temperatures were weighted by species’ covers. Low cover values of species that were gained or lost over the study period and their similar species-specific temperatures to resident species explained the discrepancy between the thermophilization detected in either cover-weighted or unweighted models.

Synthesis.Our work shows that plant species are shifting to higher elevations along roadsides in the western Swiss Alps and that this translates into a detectable warming signal of plant communities within 10 years. However, the species-level range shifts and the community-level warming effect are mostly based on low cover values of gained/lost species, preventing the detection of community thermophilization signals when incorporating cover changes. We therefore recommend using unweighted approaches for early detection of community-level responses to changing climate, ideally set into context by also assessing species-level range shifts.
Dysregulation of gene expression during gastrulation results in impaired primitive erythropoiesis and vascular development in Trim71-KO embryos
Authors: Beckröge Tobias , Jux Bettina , Seifert Hannah , Theobald Hannah , De Domenico Elena , Paulusch Stefan , Beyer Marc , Schlitzer Andreas , Mass Elvira , Kolanus Waldemar
Published: July 2024

The transition of an embryo from gastrulation to organogenesis requires precisely coordinated changes in gene expression. The RNA-binding protein Trim71 is essential for embryonic survival, but its exact role in mammalian developmentin vivoremains poorly defined. Here we show that murineTrim71-KO embryos appear normal until embryonic day (E)8.5 but display severe defects in primitive erythropoiesis, yolk sac vasculature and heart function during the onset of organogenesis at E9.5 and E10.5. This led to an impaired vascular translocation of yolk sac-derived macrophage progenitors to the embryo head, independent of Trim71 expression in erythro-myeloid progenitors. The cardiovascular and erythropoiesis defects explain the embryonic lethality upon globalTrim71-KO. TargetingTrim71in hematoendothelial progenitors did not induce strong developmental defects, indicating an earlier developmental origin of these phenotypes inTrim71-KO embryos. ScRNA-seq of E7.5Trim71-KO embryos revealed that transcriptomic changes arise already at gastrulation, showing a strong upregulation of the transcription factor Eomes. We identify Eomes as a direct target of Trim71-mediated mRNA repression via the NHL domain, demonstrating a functional link of Trim71 to a key regulator of mesodermal development. Taken together, our data suggest that Trim71-dependent control of gene expression at gastrulation establishes a framework for proper development during organogenesis.
Long-term population dynamics of an endangered butterfly are influenced by hurricane-mediated disturbance
Authors: Steele Cabrera Sarah R. , Belitz Michael , Emmel Thomas C. , Khazan Emily S. , Standridge Matthew J. , Rossetti Kristin , Daniels Jaret C.
Published: July 2024

Effective species conservation requires understanding an organism’s population dynamics and natural history, but long-term data are challenging to collect and maintain. As a result, conservation management decisions are frequently made using short-term data, which are insufficient to accurately assess population trends in most species. For less-studied taxa, including most invertebrates, inadequate understanding of life and natural history also impedes conservation efforts. Long-term studies are highly valuable for improving conservation decisions for target species as they serve as a model for other understudied species. We use mark-recapture data collected over 35 years to examine weather drivers of population patterns for an endangered butterfly, Schaus’ swallowtail (Heraclides ponceana), and to enhance our understanding of its natural history. We show that the population size of Schaus’ swallowtail butterfly was highly variable, ranging from under 100 to over 10,000 individuals. Population size is influenced by weather events and population size in the previous year. Population size was lower immediately following high wind events but was positively influenced by high wind events four years prior, with notable population increases following tropical cyclone events. Precipitation during the dry season preceding the adult flight period was also associated with higher population sizes. This study reveals the potentially beneficial role of hurricane-mediated disturbance on Schaus’ swallowtail populations potentially due to increased treefall gaps and the resulting shifts in plant communities. This remarkable data set represents one of the longest-term studies on a tropical insect.
Tracking changes in functionality and morphology of repopulated microglia in young and old mice
Authors: Luczak-Sobotkowska Zuzanna M. , Rosa Patrycja , Banqueri Lopez Maria , Ochocka Natalia , Kiryk Anna , Lenkiewicz Anna M. , Furhmann Martin , Jankowski Aleksander , Kaminska Bozena
Published: July 2024

Microglia (MG) are myeloid cells of the central nervous system supporting its homeostasis and instigating neuroinflammation in pathologies. Single-cell RNA sequencing (scRNA-seq) revealed the functional heterogeneity of MG in mice brains. Inhibition of colony-stimulating factor 1 receptor (CSF1R) signaling with inhibitors deplete microglia which rapidly repopulate. Functionalities of repopulated microglia are poorly known. We combined scRNA-seq, bulk RNA-seq, immunofluorescence and confocal imaging to study functionalities and morphology of repopulated microglia. CSRF1R inhibitor (BLZ-945) depleted MG in 21 days and their numbers were restored 7 days later as evidenced by TMEM119 staining and flow cytometry. ScRNA-seq and computational analyses demonstrate that repopulated MG originate from preexisting MG progenitors and reconstitute functional clusters but upregulate inflammatory genes. Percentages of proliferating, immature MG displaying inflammatory gene expression increase in aging mice. Morphometric analysis of MG cell body and branching shows distinct morphology of repopulated MG, particularly in old mouse brains. We demonstrate that with aging some repopulated MG fail to reach the homeostatic phenotype. These differences microglia may contribute to the deterioration of microglia protective functions with age.
A moderate water deficit induces profound changes in the proteome of developing maize ovaries
Authors: Ashenafi Mariamawit , Balliau Thierry , Blein-Nicolas Mélisande , Turc Olivier , Zivy Michel , Marchadier Elodie
Published: July 2024

Water deficit is a major cause of yield loss for maize (Zea mays), leading to ovary abortion when applied at flowering time. To help understand the mechanisms involved in this phenomenon, the proteome response to water deficit has been analysed in developing ovaries at silk emergence stage and five days later. Differential analysis, abundance pattern clustering and coexpressions networks were performed in order to draw a general picture of the proteome changes all along ovary development and under the effect of water deficit. The results show that, even mild, water deficit has a major impact on ovary proteome, but that this impact is very different from a response to a stress. A part of the changes can be related to a slowdown of ovary development, while another part cannot. In particular, ovaries submitted to water deficit show an increase in proteins involved in protein biosynthesis and in vesicle transport together with a decrease in proteins involved in amino acid metabolism and proteolysis. According to the functions of increased proteins, the changes may be linked to auxin, brassinosteroids and jasmonate signalling, but not abscisic acid.
A new alignment-free method: Subsequence Correlation Coefficient Vector(SCCFV) for influenza A comparison using virus genomes
Authors: He Lily , Yu Zhenglong , Wu Xinrui , Zhu Yi
Published: July 2024

Influenza viruses remain a formidable threat to global public health due to their high mutability and infectivity. Accurate prediction of influenza virus subtypes is crucial for clinical treatment and disease prevention. In recent years, machine learning methods have played an important role in studying influenza viruses. This study proposes a new alignment-free method based on the correlation of k-grams called Subsequence Correlation Coefficient Vector (SCCFV) to subtype hemagglutinin (HA) and neuraminidase (NA) of influenza virus. In the method, each influenza virus sequence is converted to four time series and the correlation coefficients of time series are utilized to extract the features of sequences. Then the supervised learning methods are used for the subtype classification of influenza viruses. We compare the effectiveness of the random forest, decision tree and support vector machine classifiers. Experimental results show that the random forest method achieves the best performance with an accuracy of 0.99979, an precision of 0.99996 and a recall of 0.99997. All prediction indicators of our method are significantly higher than traditional methods.
Visual system structural and functional connections during face viewing in body dysmorphic disorder
Authors: Wong Wan-wa , Peel Hayden , Cabeen Ryan , Diaz-Fong Joel P. , Feusner Jamie D.
Published: July 2024

Background

Individuals with body dysmorphic disorder (BDD) perceive distortions in their appearance, which could be due to imbalances in global and local visual processing. The vertical occipital fasciculus connects dorsal and ventral visual stream regions, integrating global and local information, yet the role of this structural connection in BDD has not been explored. Here, we investigated the vertical occipital fasciculus’s white matter microstructure in those with BDD and healthy controls and tested associations with psychometric measures and effective connectivity while viewing their face during fMRI.

Methods

We analyzed diffusion MRI and fMRI data in 17 unmedicated adults with BDD and 21 healthy controls. For diffusion MRI, bundle-specific analysis was performed, enabling quantitative estimation of neurite density and orientation dispersion of the vertical occipital fasciculus. For task fMRI, participants naturalistically viewed photos of their own face, from which we computed effective connectivity from dorsal to ventral visual regions.

Results

In BDD, neurite density was negatively correlated with appearance dissatisfaction and negatively correlated with effective connectivity. Further, those with weaker effective connectivity while viewing their face had worse BDD symptoms and worse insight. In controls, no significant relationships were found between any of the measures. There were no significant group differences in neurite density or orientation dispersion.

Conclusion

Those with BDD with worse appearance dissatisfaction have a lower fraction of tissue having axons or dendrites along the vertical occipital fasciculus bundle, possibly reflecting impacting the degree of integration of global and local visual information between the dorsal and ventral visual streams. These results provide early insights into how the vertical occipital fasciculus’s microstructure relates to the subjective experience of one’s appearance, as well as the possibility of distinct functional-structural relationships in BDD.
Macrophage-derived CCL24 promotes fibrosis and worsens cardiac dysfunction during heart failure
Authors: Parthiban Preethy , Barrow Fanta , Nguyen Huy , Neto Fernando , Florczak Kira , Wang Haiguang , Yucel Dogacan , Liu Hong , Draxler Micah , Ciske Erin , Fredrickson Gavin , Herman Adam , Rothenberg Marc E. , Dudley Samuel , van Berlo Jop , Revelo Xavier S.
Published: July 2024

Inflammation is a significant risk factor and contributes to cardiovascular disease by driving both adaptive and maladaptive processes. Macrophages are the most abundant immune cells in the heart and play an important role in the remodeling of cardiac tissue. We have previously shown an overall protective function of resident cardiac macrophages after pressure-overloaded injury. However, a subpopulation of resident macrophages also expresses high levels of the profibrotic CC motif chemokine ligand 24 (CCL24), suggesting a dichotomous role in pressure overload-induced cardiac remodeling. Here, we report that following transverse aortic constriction CCL24 knockout (CCL24 KO) mice have improved systolic function, cardiac wall enlargement, as well as increased myocyte surface area and hypertrophy, suggesting that CCL24 disrupts compensatory hypertrophy. TAC-operated CCL24 KO mice also displayed reduced fibrosis and diminished expression of fibrotic genes, implying a pro-fibrotic role for CCL24. Indeed, CCL24 induced the proliferation and activation of primary mouse fibroblasts in a process that required CCR3, the sole G protein-coupled receptor for CCL24. Correspondingly, selective ablation of CCR3 in fibroblasts improved cardiac function and ameliorated fibrosis following pressure overload. Administration of a CCL24 blocking antibody or a CCR3 antagonist both improved cardiac function in pressure-overloaded mice, highlighting the CCL24-CCR3 axis as a potential therapeutic target for heart failure. Finally, CCL24 deficiency improved cardiac function and ameliorated fibrosis during physiological aging. Overall, these results show that macrophage-derived CCL24 aggravates fibrosis via the CCR3 receptor, leading to impaired cardiac function in acute and chronic heart failure.
Highly quantitative measurement of differential protein-genome binding with PerCell chromatin sequencing
Authors: Tallan Alexi , Kucinski Jack , Sunkel Benjamin , Taslim Cenny , LaHaye Stephanie , Liu Qi , Qi Jun , Wang Meng , Kendall Genevieve C. , Stanton Benjamin Z.
Published: July 2024

We report a universal strategy for 2D chromatin sequencing, to increase uniform data analyses and sharing across labs, and to facilitate highly quantitative comparisons across experimental conditions. Within our system, we provide wetlab and drylab tools for researchers to establish and analyze protein-genome binding data with PerCell ChIP-seq. Our methodology is virtually no cost and flexible, enabling rapid, quantitative, internally normalized chromatin sequencing to catalyze project development in a variety of systems, including in vivo zebrafish epigenomics and cancer cell epigenomics. While we highlight utility in these key areas, our methodology is flexible enough such that rapid comparisons of cellular spike-in versus non spike-in are possible, and generalizability to nuclease-based 2D chromatin sequencing would also be possible within the framework of our pipeline. Through the use of well-defined cellular ratios containing orthologous species’ chromatin, we enable cross-species comparative epigenomics and highly quantitative low-cost chromatin sequencing with utility across a range of disciplines.
A Novel Registration Framework for Aligning Longitudinal Infant Brain Tensor Images
Authors: Duan Kuaikuai , Li Longchuan , Calhoun Vince D. , Shultz Sarah
Published: July 2024

Registering longitudinal infant brain images is challenging, as the infant brain undergoes rapid changes in size, shape and tissue contrast in the first months and years of life. Diffusion tensor images (DTI) have relatively consistent tissue properties over the course of infancy compared to commonly used T1 or T2- weighted images, presenting great potential for infant brain registration. Moreover, groupwise registration has been widely used in infant neuroimaging studies to reduce bias introduced by predefined atlases that may not be well representative of samples under study. To date, however, no methods have been developed for groupwise registration of tensor-based images. Here, we propose a novel registration approach to groupwise align longitudinal infant DTI images to a sample-specific common space. Longitudinal infant DTI images are first clustered into more homogenous subgroups based on image similarity using Louvain clustering. DTI scans are then aligned within each subgroup using standard tensor-based registration. The resulting images from all subgroups are then further aligned onto a sample-specific common space. Results show that our approach significantly improved registration accuracy both globally and locally compared to standard tensor-based registration and standard fractional anisotropy-based registration. Additionally, clustering based on image similarity yielded significantly higher registration accuracy compared to no clustering, but comparable registration accuracy compared to clustering based on chronological age. By registering images groupwise to reduce registration bias and capitalizing on the consistency of features in tensor maps across early infancy, our groupwise registration framework facilitates more accurate alignment of longitudinal infant brain images.
Modeling plant-microbe interactions with species distribution models
Authors: Wang Zihui , Piché-Choquette Sarah , Lauzon Jocelyn , Ishak Sarah , Kembel Steven W.
Published: July 2024

Plants interact with diverse microorganisms that play a crucial role in plant growth and development. The diversity and distribution of plant microbiota are altered by anthropogenic environmental change, leading to subsequent impacts on ecosystems. Modeling the distribution of plant-associated microbes is critical for predicting and managing future changes in microbial function, but there remain challenges and open questions when developing these models. We present a conceptual framework for process-oriented predictive modeling of the distribution of plant-associated microbiota. We first describe different approaches to incorporating host plants into modeling microbial distributions, namely by including them as static variables, nesting them within microbial distribution models or incorporating them simultaneously via joint species distribution models. Additionally, we discuss issues associated with collecting and analyzing sequencing-based microbial data, emphasizing the importance of data normalization and careful interpretation of species distribution models. We further discuss how to incorporate evolutionary history into microbial distribution modeling. Finally, we present a case study demonstrating how incorporating host information can improve the prediction of microbial distributions. This study provides insights for predicting future distributions of plant-associated microbes under climate change and plant species redistribution, which can be generalized to other host-associated microbial systems.
Effects of leg immobilization and recovery resistance training on skeletal muscle-molecular markers in previously resistance trained versus untrained adults
Authors: Michel J. Max , Godwin Joshua S. , Plotkin Daniel L. , McIntosh Mason C. , Mattingly Madison L. , Agostinelli Philip J. , Mueller Breanna J. , Anglin Derick A. , Berry Alexander C. , Vega Marina Meyer , Pipkin Autumn A. , Stock Matt S. , Graham Zachary A. , Baweja Harsimran S. , Mobley C. Brooks , Bamman Marcas M. , Roberts Michael D.
Published: July 2024

We sought to examine how resistance training (RT) status in young healthy individuals, either well-trained (T, n=10 (8 males)) or untrained (UT, n=11 (8 males)), affected muscle size and molecular markers with leg immobilization followed by recovery RT. All participants underwent two weeks of left leg immobilization via the use of crutches and a locking leg brace. After this two-week period, all participants underwent eight weeks (3 d/week) of knee extensor focused progressive RT. Vastus lateralis (VL) ultrasound-derived thickness and muscle cross-sectional area were measured at baseline (PRE), immediately after disuse (MID), and after RT (POST) with VL muscle biopsies collected at these time points. T and UT presented lower ultrasound derived VL size (cross-sectional area and thickness) values at MID versus PRE (p≤0.001), and values increased in both groups from MID to POST (p<0.05); however, VL size increased from PRE to POST in UT only (p<0.001). Mean and type II myofiber cross-sectional area (fCSA) values demonstrated a main effect of time where PRE and POST were greater than MID (p<0.05) and main effect of training status where T was greater than UT (P≤0.012). In both groups, satellite cell number was not affected by leg immobilization but increased in response to RT (p≤0.014), with T being greater than UT across all time points (p=0.004). Additionally, ribosome content (total RNA) decreased (p=0.010) from PRE to MID while the endoplasmic reticulum stress proteins (BiP, Xbp1s, and CHOP) increased from MID to POST regardless of training status. Finally, the phosphorylation states of mechanistic target of rapamycin complex-1 signaling proteins were not significantly altered for either group throughout the intervention. In conclusion, immobilization-induced muscle atrophy and recovery RT hypertrophy outcomes are similar between UT and T participants, and the lack of molecular signature differences between groups supports these findings. However, these data are limited to younger adults undergoing non-complicated disuse. Thus, further investigation to determine the impact of training status on prolonged leg immobilization models mirroring current medical protocols (e.g., following orthopedic injury and surgery) is warranted.