bluuebunny/crossref_metadata_2025_split huggingface dataset:
Positionally distinct interferon stimulated dermal immune acting fibroblasts promote neutrophil recruitment in Sweet’s syndrome
Authors: Cavagnero Kellen J. , Albright Julie , Li Fengwu , Dokoshi Tatsuya , Bogle Rachael , Kirma Joseph , Kahlenberg J. Michelle , Billi Allison C. , Fox Jennifer , Coon Anthony , Dobry Craig J. , Hinds Brian , Tsoi Lam C. , Harms Paul W. , Gudjonsson Johann E. , Gallo Richard L. 
Published: June 2024

AbstractSweet’s syndrome is a poorly understood inflammatory skin disease characterized by neutrophil infiltration to the dermis. Single-nucleus and bulk transcriptomics of archival clinical samples of Sweet’s syndrome revealed a prominent interferon signature in Sweet’s syndrome skin that was reduced in tissue from other neutrophilic dermatoses. This signature was observed in different subsets of cells, including fibroblasts that expressed interferon-induced genes. Functionally, this response was supported by analysis of cultured primary human dermal fibroblasts that were observed to highly express neutrophil chemokines in response to activation by type I interferon. Furthermore, single-molecule resolution spatial transcriptomics of skin in Sweet’s syndrome identified positionally distinct immune acting fibroblasts that included a CXCL1+ subset proximal to neutrophils and a CXCL12+ subset distal to the neutrophilic infiltrate. This study defines the cellular landscape of neutrophilic dermatoses and suggests dermal immune acting fibroblasts play a role in the pathogenesis of Sweet’s syndrome through recognition of type I interferons.
Translational control in the spinal cord regulates gene expression and pain hypersensitivity in the chronic phase of neuropathic pain
Authors: Lister Kevin C. , Wong Calvin , Uttam Sonali , Parisien Marc , Stecum Patricia , Brown Nicole , Cai Weihua , Hooshmandi Mehdi , Gu Ning , Amiri Mehdi , Beaudry Francis , Jafarnejad Seyed Mehdi , Tavares-Ferreira Diana , Inturi Nikhil Nageshwar , Mazhar Khadijah , Zhao Hien T. , Fitzsimmons Bethany , Gkogkas Christos G. , Sonenberg Nahum , Price Theodore J. , Diatchenko Luda , Atlasi Yaser , Mogil Jeffrey S. , Khoutorsky Arkady 
Published: June 2024

SummarySensitization of spinal nociceptive circuits plays a crucial role in neuropathic pain. This sensitization depends on new gene expression that is primarily regulated via transcriptional and translational control mechanisms. The relative roles of these mechanisms in regulating gene expression in the clinically relevant chronic phase of neuropathic pain are not well understood. Here, we show that changes in gene expression in the spinal cord during the chronic phase of neuropathic pain are substantially regulated at the translational level. Downregulating spinal translation at the chronic phase alleviated pain hypersensitivity. Cell-type-specific profiling revealed that spinal inhibitory neurons exhibited greater changes in translation after peripheral nerve injury compared to excitatory neurons. Notably, increasing translation selectively in all inhibitory neurons or parvalbumin-positive (PV+) interneurons, but not excitatory neurons, promoted mechanical pain hypersensitivity. Furthermore, increasing translation in PV+neurons decreased their intrinsic excitability and spiking activity, whereas reducing translation in spinal PV+neurons prevented the nerve injury-induced decrease in excitability. Thus, translational control mechanisms in the spinal cord, particularly in inhibitory neurons, play a role in mediating neuropathic pain hypersensitivity.
Lipidic and senescent macrophages predict progression and response to combinatorial immunotherapy in triple-negative breast cancer
Authors: Chan Chun Lai , To Alex , Zhang Shihui , Wong Jason Wing Hon , Huang Yuanhua , Chao Yiming , Sugimura Ryohichi 
Published: June 2024

AbstractImmune cell subsets in the tumor predict prognosis. Identifying reliable subsets consistently in multiple patients is clinically important. What’s more advantageous to the field is if such subsets can be a target of immunotherapy. Here we analyzed single-cell RNA-sequencing datasets of patients with triple-negative breast cancer and identified APOE or FABP5-expressing macrophages correlated with poor prognosis. Further validation with TCGA-BRCA cohort detailed molecular signatures of these macrophages as lipidic and senescent. Our receptor-ligand mapping identified lipidic and senescent macrophages both suppress T-lymphoid and myeloid immunogenicity. Finally, we discovered that immune checkpoint therapy combined with chemotherapy reprogrammed anti-tumor microenvironment enriched with FOLR2+macrophages facilitated T-cell activations. This suggests that lipidic and senescent macrophages could be a therapeutic target of immune checkpoint therapy.
AB-free kava enhances resilience against the adverse health effects of tobacco smoke in mice
Authors: Bian Tengfei , Lynch Allison , Ballas Kayleigh , Mamallapalli Jessica , Freeman Breanne , Scala Alexander , Wang Yifan , Trabouls Hussein , Chellian Ranjith kumar , Fagan Amy , Tang Zhixin , Ding Haocheng , De Umasankar , Fredenburg Kristianna M. , Huo Zhiguang , Baglole Carolyn J. , Zhang Weizhou , Reznikov Leah R. , Bruijnzeel Adriaan W. , Xing Chengguo 
Published: June 2024

ABSTRACTTobacco smoke remains a serious global issue, resulting in serious health complications, contributing to the onsets of numerous preventive diseases, and imposing significant financial burdens. Despite regulatory policies and cessation measures aimed at curbing its usage, novel interventions are urgently needed for effective damage reduction. Our preclinical and pilot clinical studies showed that AB-free kava has the potential to reduce tobacco smoke-induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use. To understand the scope of its benefits in damage reduction and potential limitations, this study evaluated the effects of AB-free kava on a panel of health indicators in mice exposed to 2 – 4 weeks of daily tobacco smoke exposure. Our comprehensive assessments included global transcriptional profiling of the lung and liver tissues, analysis of lung inflammation, evaluation of lung function, exploration of tobacco nicotine withdrawal, and characterization of the causal PKA signaling pathway. As expected, Tobacco smoke exposure perturbed a wide range of biological processes and compromised multiple functions in mice. Remarkably, AB-free kava demonstrated the ability to globally mitigate tobacco smoke-induced deficits at the molecular and functional levels with promising safety profiles, offering a unique promise to mitigate tobacco smoke-related health damages. Further pre-clinical evaluation and clinical translation are warranted to fully harness the potential of AB-free kava in combating tobacco smoke-related harms.Graphical Abstract
Methionine Restriction Reduces Lung Cancer Progression and Increases Chemotherapy Response
Authors: Naughton Kassandra J. , Song Xiulong , Childress Avery R. , Skaggs Erika M. , Byrd Aria L. , Gosser Christian M. , Esoe Dave-Preston , DuCote Tanner J. , Plaugher Daniel R. , Lukyanchuk Alexsandr , Goettl Ryan A. , Liu Jinpeng , Brainson Christine F. 
Published: June 2024

ABSTRACTTargeting tumor metabolism through dietary interventions is an area of growing interest, and may help to improve the significant mortality of aggressive cancers, including non-small cell lung cancer (NSCLC). Here we show that the restriction of methionine in the aggressive KRAS/Lkb1-mutant NSCLC autochthonous mouse model drives decreased tumor progression and increased carboplatin treatment efficacy. Importantly, methionine restriction during early stages of tumorigenesis prevents the lineage switching known to occur in the model, and alters the tumor immune microenvironment (TIME) to have fewer tumor-infiltrating neutrophils. Mechanistically, mutations inLKB1are linked to anti-oxidant production through changes to cystathionine-β-synthase (CBS) expression. Human cell lines with rescuedLKB1show increased CBS levels and resistance to carboplatin, which can be partially rescued by methionine restriction. Furthermore, LKB1 rescued cells, but not mutant cells, show less G2- M arrest and apoptosis in high methionine conditions. Knock-down of CBS sensitized both LKB1 mutant and non-mutated lines to carboplatin, again rescuing the carboplatin resistance of the LKB1 rescued lines. Given that immunotherapy is commonly combined with chemotherapy for NSCLC, we next wanted to understand if T cells are impaired by MR. Therefore, we examined the ability of T cells from MR and control tumor bearing mice to proliferate in culture and found that T cells from MR treated mice had no defects in proliferation, even though we continued the MR conditionsex vivo. We also identified that CBS is most highly correlated with smoking, adenocarcinomas with alveolar and bronchiolar features, and adenosquamous cell carcinomas, implicating its roles in oxidative stress response and lineage fate in human tumors. Taken together, we have shown the importance of MR as a dietary intervention to slow tumor growth and improve treatment outcomes for NSCLC.
Loss of AMPK potentiates inflammation by activating the inflammasome after traumatic brain injury in mice
Authors: Ahmed Mohammad Ejaz , Suhail Hamid , Nematullah Mohammad , Hoda Md Nasrul , Giri Shailendra , Ahmad Abdullah Shafique 
Published: June 2024

AbstractTraumatic brain injury (TBI) is a significant public health concern characterized by a complex cascade of cellular events. TBI induces adenosine monophosphate-activated protein kinase (AMPK) dysfunction impairs energy balance activates inflammatory cytokines and leads to neuronal damage. AMPK is a key regulator of cellular energy homeostasis during inflammatory responses. Recent research has revealed its key role in modulating the inflammatory process in TBI. Following TBI the activation of AMPK can influence various important pathways and mechanisms including metabolic pathways and inflammatory signaling. Our study investigated the effects of post-TBI loss of AMPK function on functional outcomes inflammasome activation, and inflammatory cytokine production. Male C57BL/6 adult wild-type (WT) and AMPK knockout (AMPK-KO) mice were subjected to a controlled cortical impact (CCI) model of TBI or sham surgery. The mice were tested for behavioral impairment at 24 h post-TBI thereafter, mice were anesthetized, and their brains were quickly removed for histological and biochemical evaluation.In vitrowe investigated inflammasome activation in mixed glial cells stimulated with lipopolysaccharides+ Interferon-gamma (LI) (0.1 µg/20 ng/ml LPS/IFNg) for 6 h to induce an inflammatory response. Estimating the nucleotide-binding domain, leucine-rich–containing family pyrin domain containing western blotting ELISA and qRT-PCR performed 3 (NLRP3) inflammasome activation and cytokine production. Our findings suggest that TBI leads to reduced AMPK phosphorylation in WT mice and that the loss of AMPK correlates with worsened behavioral deficits at 24 h post-TBI in AMPK-KO mice as compared to WT mice. Moreover compared with the WT mice AMPK-KO mice exhibit exacerbated NLRP3 inflammasome activation and increased expression of proinflammatory mediators such as IL-1b IL-6 TNF-a iNOS and Cox 2. These results align with thein vitrostudies using brain glial cells under inflammatory conditions, demonstrating greater activation of inflammasome components in AMPK-KO mice than in WT mice. Our results highlighted the critical role of AMPK in TBI outcomes. We found that the absence of AMPK worsens behavioral deficits and heightens inflammasome-mediated inflammation thereby exacerbating brain injury after TBI. Restoring AMPK activity after TBI could be a promising therapeutic approach for alleviating TBI-related damage.
Stereotyped spatiotemporal dynamics of spontaneous activity in visual cortex prior to eye-opening
Authors: Kettlewell Luna , Sederberg Audrey , Smith Gordon B. 
Published: June 2024

AbstractOver the course of development, functional sensory representations emerge in the visual cortex. Prior to eye-opening, modular patterns of spontaneous activity form long-range networks that may serve as a precursor for mature network organization. Although the spatial structure of these networks has been well studied, their temporal features, which may contribute to their continued plasticity and development, remain largely uncharacterized. To address this, we imaged hours of spontaneous network activity in the visual cortex of developing ferrets of both sexes utilizing a fast calcium indicator (GCaMP8m) and widefield imaging at high temporal resolution (50Hz), then segmented out spatiotemporal events. The spatial structure of this activity was highly modular, exhibiting spatially segregated active domains consistent with prior work. We found that the vast majority of events showed a clear dynamic component in which modules activated sequentially across the field of view, but only a minority of events were well-fit with a linear traveling wave. We found that spatiotemporal events occur in repeated and stereotyped motifs, reoccurring across hours of imaging. Finally, we found that the most frequently occurring single-frame spatial activity patterns were predictive of future activity patterns over hundreds of milliseconds. Together, our results demonstrate that spontaneous activity in the early developing cortex exhibits a rich spatiotemporal structure, suggesting a potential role in the maturation and refinement of future functional representations.Significance statementUnderstanding the temporal dynamics underlying the network structure in early development is critical for understanding network function and plasticity. By imaging hours of spontaneous cortical activity, we show strong evidence that the vast majority of spontaneous neural activity is dynamic with repeated and complex spatiotemporal patterns with stereotyped structure across hours. This suggests the potential for Hebbian learning in the development and refinement of functional visual representations. We also find that frequently occurring spatial activity patterns are predictive of subsequent activity for up to one second, which may indicate attractor dynamics in spontaneous activity. Our findings characterize key features of the temporal structure of spontaneous activity in visual cortex early in development and deepen our understanding of developing neural networks.
ClOneHORT: Approaches for Improved Fidelity in Generative Models of Synthetic Genomes
Authors: Laboulaye Roland , Borda Victor , Chen Shuo , North Kari E. , Kaplan Robert , O’Connor Timothy D. 
Published: June 2024

ABSTRACTMotivationDeep generative models have the potential to overcome difficulties in sharing individual-level genomic data by producing synthetic genomes that preserve the genomic associations specific to a cohort while not violating the privacy of any individual cohort member. However, there is significant room for improvement in the fidelity and usability of existing synthetic genome approaches.ResultsWe demonstrate that when combined with plentiful data and with population-specific selection criteria, deep generative models can produce synthetic genomes and cohorts that closely model the original populations. Our methods improve fidelity in the site-frequency spectra and linkage disequilibrium decay and yield synthetic genomes that can be substituted in downstream local ancestry inference analysis, recreating results with .91 to .94 accuracy.AvailabilityThe model described in this paper is freely available atgithub.com/rlaboulaye/clonehort.
Advancing coral micropropagation for coral restoration and reef engineering
Authors: Walton Emily , Badder Lindsey , Galindo-Martínez Claudia Tatiana , Berry David B. , Tresguerres Martin , Wangpraseurt Daniel 
Published: June 2024

AbstractIn the face of escalating threats posed by human-induced climate change, urgent attention to coral reef restoration is imperative due to ongoing reef degradation. Here, we explored the potential of generating coral micropropagates as a tool to rapidly generate coral tissue for reef restoration and reef engineering. We developed a hypersalinity-induced polyp bailout protocol and a simple attachment device to support the growth of micropropagates on commonly used restoration substrates. We found that hypersalinity induction, at a rate of < 1 ppt hr-1, produced healthy micropropagates of the coralStylophora pistillata. The highest attachment success (∼74%) was achieved in CaCO3substrate devices, which outperformed PVC (∼5%) and Portland cement (∼48%). Settled micropropagates displayed rapid growth rates on both CaCO3(0.037 mm2/day ± 0.002 SE) and PVC (0.057 mm2/day ± 0.008 SE) substrates, while Portland cement induced tissue degradation. Our study provides a detailed methodology for reliably generating, attaching, and growing coral micropropagates and underscores the potential of polyp bailout as a viable technique supporting coral restoration and reef engineering efforts.
Mapping the spectrotemporal regions influencing perception of French stop consonants in noise
Authors: Carranante Géraldine , Cany Charlotte , Farri Pouria , Giavazzi Maria , Varnet Léo 
Published: June 2024

ABSTRACTUnderstanding how speech sounds are decoded into linguistic units has been a central research challenge over the last century. This study follows a reverse-correlation approach to reveal the acoustic cues listeners use to categorize French stop consonants in noise. Compared to previous methods, this approach ensures an unprecedented level of detail with only minimal theoretical assumptions. Thirty-two participants performed a speech-in-noise discrimination task based on natural /aCa/ utterances, with C = /b/, /d/, /g/, /p/, /t/, or /k/. The trial-by-trial analysis of their confusions enabled us to map the spectrotemporal information they relied on for their decisions. In place-of-articulation contrasts, the results confirmed the critical role of formant consonant-vowel transitions, used by all participants, and, to a lesser extent, vowel-consonant transitions and high-frequency release bursts. Similarly, for voicing contrasts, we validated the prominent role of the voicing bar cue, with some participants also using formant transitions and burst cues. This approach revealed that most listeners use a combination of several cues for each task, with significant variability within the participant group. These insights shed new light on decades-old debates regarding the relative importance of cues for phoneme perception and suggest that research on acoustic cues should not overlook individual variability in speech perception.
Gestational CBD shapes insular cortex in adulthood
Authors: Iezzi Daniela , Cáceres-Rodríguez Alba , Silva Jessica Pereira , Chavis Pascale , Manzoni Olivier J. 
Published: June 2024

AbstractMany expectant mothers use CBD to alleviate symptoms like nausea, insomnia, anxiety, and pain, despite limited research on its long-term effects. However, CBD passes through the placenta, affecting fetal development and impacting offspring behavior. We investigated how prenatal CBD exposure affects the insular cortex (IC), a brain region involved in emotional processing and linked to psychiatric disorders. The IC is divided into two territories: the anterior IC (aIC), processing socioemotional signals, and the posterior IC (pIC), specializing in interoception and pain perception. Pyramidal neurons in the aIC and pIC exhibit sex-specific electrophysiological properties, including variations in excitability and the excitatory/inhibitory balance. We investigated IC’s cellular properties and synaptic strength in the offspring of both sexes from mice exposed to low-dose CBD during gestation (E5-E18; 3mg/kg, s.c.). Prenatal CBD exposure induced sex-specific and territory-specific changes in the active and passive membrane properties, as well as intrinsic excitability and the excitatory/inhibitory balance, in the IC of adult offspring. The data indicate that in-utero CBD exposure disrupts IC neuronal development, leading to a loss of functional distinction between IC territories. These findings may have significant implications for understanding the effects of CBD on emotional behaviors in offspring.
SLC7A5 is required for citrulline-dependent growth in arginine limited conditions
Authors: Dunlap Kyle N. , Bender Austin , Bowles Alexis , Bott Alex J. , Rutter Jared , Ducker Gregory S. 
Published: June 2024

SummaryTumor cells must optimize metabolite acquisition between synthesis and uptake from their surroundings. The tumor microenvironment is characterized by hypoxia, lactate accumulation, and depletion of many circulating metabolites, including amino acids such as arginine. We performed a metabolism-focused functional screen using CRISPR/Cas9 in a melanoma cell line to identify pathways and factors that enable tumor growth in an arginine-depleted environment. Our screen identified the SLC-family transporter SLC7A5 as required for growth, and we hypothesized that this protein functions as a high-affinity citrulline transporter. Citrulline, an essential precursor to arginine synthesis, is present in human serum at 40 μM and supports localized arginine synthesis across diverse tissues. Using isotopic tracing experiments, we show that citrulline uptake and metabolism are dependent upon expression of this transporter. Pharmacological inhibition of SLC7A5 blocks growth in low arginine conditions across a diverse group of cancer cell lines. Loss of SLC7A5 reduces tumor growth and citrulline import in a mouse tumor model. Overall, we identify a conditionally essential role for SLC7A5 in arginine metabolism as a mediator of citrulline uptake, and we propose that SLC7A5-targeting therapeutic strategies in cancer may be especially effective in the context of arginine limitation.Key PointsSLC7A5 is required for proliferation in arginine-free conditions when citrulline is present.SLC7A5 loss impairs arginine metabolism.Citrulline import is uniquely dependent on SLC7A5.Small molecule inhibitors of SLC7A5 can be paired with senolytic drugs to drive apoptosis.SLC7A5knockout decreases citrulline import in a xenograft model.
Cell type-specific regulation by different cytokinetic pathways in the early embryo
Authors: Connors Caroline Q. , Martin Sophia L. , Dumont Julien , Shirasu-Hiza Mimi , Canman Julie C. 
Published: June 2024

AbstractCytokinesis, the physical division of one cell into two, is typically assumed to use the same molecular process across animal cells. However, regulation of cell division can vary significantly among different cell types, even within the same multicellular organism. Using six fast-acting temperature-sensitive (ts) cytokinesis-defective mutants, we found that each had unique cell type-specific profiles in the earlyC. elegansembryo. Certain cell types were more sensitive than others to actomyosin and spindle signaling disruptions, disrupting two members of the same complex could result in different phenotypes, and protection against actomyosin inhibition did not always protect against spindle signaling inhibition.