bluuebunny/crossref_metadata_2025_split huggingface dataset:
Astrocytic Regulation of Cocaine Locomotor Sensitization in EcoHIV Infected Mice
Authors: Xie Qiaowei , Dasari Rohan , Namba Mark D. , Buck Lauren A. , Side Christine M. , Park Kyewon , Jackson Joshua G. , Barker Jacqueline M. 
Published: September 2024

AbstractCocaine use disorder (CUD) is highly comorbid with HIV infection and worsens HIV outcomes. Preclinical research on the outcomes of HIV infection may yield crucial information on neurobehavioral changes resulting from chronic drug exposure in people living with HIV (PLWH). Repeated exposure to cocaine alters behavioral responses to cocaine. This includes development of cocaine locomotor sensitization – or increased locomotor responses to the same doses of cocaine - which depends on nucleus accumbens (NAc) neural plasticity. NAc astrocytes are key regulators of neural activity and plasticity, and their function can be impaired by cocaine exposure and HIV infection, thus implicating them as potential regulators of HIV-induced changes in behavioral response to cocaine. To characterize the effects of HIV infection on cocaine locomotor sensitization, we employed the EcoHIV mouse model to assess changes in locomotor responses after repeated cocaine (10mg/kg) exposure and challenge. EcoHIV infection potentiated expression of cocaine sensitization. We also identified EcoHIV-induced increases in expression of the astrocytic nuclear marker Sox9 selectively in the NAc core. To investigate whether modulation of NAc astrocytes could reverse EcoHIV-induced deficits, we employed a chemogenetic approach. We found that chemogenetic activation of NAc astrocyte Gq signaling attenuated EcoHIV-enhanced cocaine sensitization. We propose that HIV infection contributes to cocaine behavioral sensitization and induces adaptations in NAc astrocytes, while promoting NAc astrocytic Gq-signaling can recover EcoHIV-induced behavioral changes. These findings identify potential cellular substrates of disordered cocaine-driven behavior in the context of HIV infection and point toward strategies to reduce cocaine-related behavior in PLWH.
Rhizobacteria prime the activation of defence and nutritional responses to suppress aphid populations on barley
Authors: Mbaluto Crispus M. , Zytynska Sharon E. 
Published: September 2024

SummaryInteractions between plant and soil microbes are widespread and modulate plant-insect herbivore interactions. Still, it remains unclear how these shapes the overall plant defence responses and the mechanisms involved.Here, we performed bioassays with barley (Hordeum vulgare) plants to study the underlying molecular pathways induced by two rhizobacteria,Acidovorax radicisorBacillus subtilis,against the phloem feeding aphidSitobion avenaeover three timepoints.Root colonization byA. radicisorB. subtilissuppressed aphid populations on barley. Analysis of differentially expressed genes and co-expressed gene modules revealed a combination of rhizobacteria and aphid induced plant responses. Aphid feeding triggered distinct plant responses in rhizobacteria-inoculated barley compared to controls, in phytohormone, glutathione, and phenylpropanoid pathways within 24 hours. By day 7, stronger responses were observed in phenylpropanoid and nutrient pathways. By day 21, changes occurred in flavonoid pathways and genes related to tissue damage and repair.Our study suggests that rhizobacteria inoculation of barley against aphids is dynamic and acts through several molecular pathways to induce plant resistance (defences) and tolerance (nutrition and growth) to aphids. Future research holds promise for exploiting these interactions for sustainable crop protection and pest management in agriculture.
The flexible stalk domain of sTREM2 modulates its interactions with phospholipids in the brain
Authors: Saeb David , Lietzke Emma E. , Fuchs Daisy I. , Aldrich Emma C. , Bruce Kimberley D. , Sprenger Kayla G. 
Published: September 2024

AbstractThe microglial surface protein Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) plays a critical role in mediating brain homeostasis and inflammatory responses in Alzheimer’s disease (AD). The soluble form of TREM2 (sTREM2) exhibits neuroprotective effects in AD, though the underlying mechanisms remain elusive. Moreover, differences in ligand binding between TREM2 and sTREM2, which have major implications for their roles in AD pathology, remain unexplained. To address these knowledge gaps, we conducted the most computationally intensive molecular dynamics simulations to date of (s)TREM2, exploring their interactions with key damage- and lipoprotein-associated phospholipids and the impact of the AD-risk mutation R47H. Our results demonstrate that the flexible stalk domain of sTREM2 serves as the molecular basis for differential ligand binding between sTREM2 and TREM2, facilitated by its role in stabilizing the Ig-like domain and altering the accessibility of canonical ligand binding sites. We identified a novel ligand binding site on sTREM2, termed the ‘Expanded Surface 2’, which emerges due to competitive binding of the stalk with the Ig-like domain. Additionally, we observed that the stalk domain itself functions as a site for ligand binding, with increased binding in the presence of R47H. This suggests that sTREM2’s neuroprotective role in AD may, at least in part, arise from the stalk domain’s ability to rescue dysfunctional ligand binding caused by AD-risk mutations. Lastly, our findings indicate that R47H-induced dysfunction in membrane-bound TREM2 may result from both diminished ligand binding due to restricted complementarity-determining region 2 loop motions and an impaired ability to differentiate between ligands, proposing a novel mechanism for loss-of-function. In summary, these results provide valuable insights into the role of sTREM2 in AD pathology, laying the groundwork for the design of new therapeutic approaches targeting (s)TREM2 in AD.
New loci and candidate genes in spring two-rowed barley detected through meta-analysis of a field trial European network
Authors: Montardit-Tarda Francesc , Casas Ana M , Thomas William TB , Schnaithmann Florian , Sharma Rajiv , Shaaf Salar , Campoli Chiara , Russell Joanne , Ramsay Luke , Delbono Stefano , Jääskeläinen Marko , Paul Maitry , Stoddard Frederick L , Visioni Andrea , Flavell Andrew J , Pillen Klaus , Kilian Benjamin , Graner Andreas , Rossini Laura , Waugh Robbie , Cattivelli Luigi , Schulman Alan H , Tondelli Alessandro , Igartua Ernesto 
Published: September 2024

AbstractThis study contributes new knowledge on quantitative trait loci (QTLs) and candidate genes for adaptive traits and yield in two-rowed spring barley. A meta-analysis of a network of field trials, varying in latitude and sowing date, with 151 cultivars across several European countries, increased QTL detection power compared to single-trial analyses. The traits analysed were heading date (HD), plant height (PH), thousand-grain weight (TGW), and grain yield (GY). Breaking down the analysis by the main genotype-by-environment trends revealed QTLs and candidate genes specific to conditions like sowing date and latitude. A historical look on the evolution of QTL frequencies revealed that early selection focused on PH and TGW, likely due to their high heritability. GY selection occurred later, facilitated by reduced variance in other traits. The study observed that favourable alleles for plant height were often fixed before those for grain yield and TGW. Some regions showed linkage in repulsion, suggesting targets for future breeding. Several candidate genes were identified, including known genes and new candidates based on orthology with rice. Remarkably, thedeficiensallele of geneVrs1, appears associated to higher GY. These findings provide valuable insights for barley breeders aiming to improve yield, and other agronomic traits.HighlightA dense genome-wide meta-analysis provides new QTLs, reveals breeding history trends and identifies new candidate genes for yield, plant height, grain weight and heading time of spring barley.
A generalizable normative deep autoencoder for brain morphological anomaly detection: application to the multi-site StratiBip dataset on bipolar disorder in an external validation framework
Authors: Sampaio Inês Won , Tassi Emma , Bellani Marcella , Benedetti Francesco , Nenadic Igor , Phillips Mary , Piras Fabrizio , Yatham Lakshmi , Bianchi Anna Maria , Brambilla Paolo , Maggioni Eleonora 
Published: September 2024

AbstractThe heterogeneity of psychiatric disorders makes researching disorder-specific neurobiological markers an ill-posed problem. Here, we face the need for disease stratification models by presenting a generalizable multivariate normative modelling framework for characterizing brain morphology, applied to bipolar disorder (BD). We employed deep autoencoders in an anomaly detection framework, combined with a confounder removal step integrating training and external validation.The model was trained with healthy control (HC) data from the human connectome project and applied to multi-site external data of HC and BD individuals. We found that brain deviating scores were greater, more heterogeneous, and with increased extreme values in the BD group, with volumes prominently from the basal ganglia, hippocampus and adjacent regions emerging as significantly deviating. Similarly, individual brain deviating maps based on modified z scores expressed higher abnormalities occurrences, but their overall spatial overlap was lower compared to HCs.Our generalizable framework enabled the identification of subject- and group-level brain normative-deviating patterns, a step forward towards the development of more effective and personalized clinical decision support systems and patient stratification in psychiatry.
Next-generation Cu(II) selective peptide shuttles prevent Cu(Aβ)-induced toxicity and microglial activation in organotypic hippocampal slices
Authors: Okafor Michael , Schmitt David , Gasman Stéphane , Raibaut Laurent , Hureau Christelle , Faller Peter , Vitale Nicolas 
Published: September 2024

AbstractAlzheimer’s disease (AD) remains the most prevalent neurodegenerative disease with hallmarks including the apparition, in specific areas of the brain, of intracellular neurofibrillary tangles and extracellular amyloid plaques. The latter result from an abnormal metabolism of Amyloid-β precursor protein (APP) leading to its accumulation in plaques.Ex vivoanalysis of AD patients’ brains, show an abnormally elevated concentration of metals including Cu, Zn and Fe in these plaques. Some studies have also demonstrated altered Cu levels in the entire brain and more specifically in regions heavily affected in AD. These modifications are often accompanied by a decline in neuronal Cu levels and by an increase in the proportion of extracellular labile Cu, which in turn promotes reactive oxygen species formation. To correct this Cu dyshomeostasis, we designed and synthesized novel Cu(II)-selective peptide shuttles, capable of swiftly retrieving Cu from extracellular Aβ and subsequently transporting and releasing Cu inside cells. We demonstrate here the capacity of this new Cu-shuttles, DapHH-αR5W4NBDand HDapH-αR5W4NBD, to protect organotypic hippocampal slices (OHSCs) from Cu(Aβ)-induced insult and their capability to rescues Cu-induced microglial activation and proliferation.
Humidity as a zeitgeber for circadian entrainment of insect systems
Authors: Chen Shyh-Chi , Goodhart Grace , Eaton Daniel , Catlett Nathan , Cady Tabitha , Tran Hannah , Lutz Luke E. , Wang Lyn , Girard Ella , Savino Jaida , Perry Jodi , Hall Libby , Bidiwala Amena , Tarter Emma , Tompkin Joshua , Greene Nina , Benoit Joshua B. 
Published: September 2024

AbstractHumidity levels, like light and temperature, fluctuate daily yet are less predictable; however, whether humidity entrains circadian clocks and enables animals to synchronize behaviors to environmental variations remains unknown. Here, we investigate the circadian humidity entrainment in various insects. Multiple species robustly respond to humidity cycles, and when the humidity cue is removed, their rhythmic behaviors continue, suggesting that humidity-associated rhythmic activities are under circadian control. Moreover, theDrosophilaclock and hygrosensation mutants lack rhythmic activities during and after humidity entrainment, indicating that the core clock components and hygrosensors are essential to circadian entrainment. Our findings identify that humidity serves as a novel zeitgeber for circadian entrainment for insects that could have broad applicability and importance among animal systems.One Sentence SummaryHumidity entrainment of the circadian clock enables the synchronization of insect behaviors to environments.
Metapipeline-DNA: A Comprehensive Germline & Somatic Genomics Nextflow Pipeline
Authors: Patel Yash , Zhu Chenghao , Yamaguchi Takafumi N. , Wang Nicholas K. , Wiltsie Nicholas , Gonzalez Alfredo E. , Winata Helena K. , Zeltser Nicole , Pan Yu , Mootor Mohammed Faizal Eeman , Sanders Timothy , Kandoth Cyriac , Fitz-Gibbon Sorel T. , Livingstone Julie , Liu Lydia Y. , Carlin Benjamin , Holmes Aaron , Oh Jieun , Sahrmann John , Tao Shu , Eng Stefan , Hugh-White Rupert , Pashminehazar Kiarod , Park Andrew , Beshlikyan Arpi , Jordan Madison , Wu Selina , Tian Mao , Arbet Jaron , Neilsen Beth , Bugh Yuan Zhe , Kim Gina , Salmingo Joseph , Zhang Wenshu , Haas Roni , Anand Aakarsh , Hwang Edward , Neiman-Golden Anna , Steinberg Philippa , Zhao Wenyan , Anand Prateek , Tsai Brandon L. , Boutros Paul C. 
Published: September 2024

AbstractSummaryDNA sequencing continues to get cheaper and faster. In parallel, algorithmic innovations have allowed inference of a wide range of nuclear, mitochondrial, somatic and evolutionary from DNA sequencing data. To make automated, high-quality DNA sequencing more readily available, we created an extensible Nextflow meta-pipeline called metapipeline-DNA. Metapipeline-DNA supports processing raw sequencing reads through alignment, variant detection, quality control and subclonal reconstruction. Each step supports quality-control, data-visualization and multiple algorithms. Metapipeline-DNA is cloud-compatible and highly configurable, with options to subsect, optimize and optimize analyses, including with automated failure-recovery. Metapipeline-DNA enables high-scale, fault-tolerant, comprehensive analysis of genome sequencing.AvailabilityMetapipeline-DNA is an open-source Nextflow pipeline under the GPLv2 license and is available athttps://github.com/uclahs-cds/metapipeline-DNA.
Restoration of 3-D structure of insect flight muscle from a rotationally averaged 2-D X-ray diffraction pattern
Authors: Iwamoto Hiroyuki 
Published: September 2024

AbstractThe contractile machinery of muscle, especially that of skeletal muscle, has a very regular array of contractile protein filaments, and gives rise to a complex and informative diffraction pattern when irradiated with X-rays. However, analyzing these diffraction patterns is often challenging because: (1) only rotationally averaged diffraction patterns can be obtained, resulting in a substantial loss of information, and (2) the contractile machinery contains two different sets of protein filaments (actin and myosin) with different helical symmetries. The reflections originating from them often overlap. These problems may be solved if the real-space 3-D structure of the contractile machinery is directly calculated from the diffraction pattern. Here we demonstrate that, by using the conventional phase-retrieval algorithm (hybrid input-output), the real-space 3-D structure of the contractile machinery can be effectively restored from a single rotationally averaged 2-D diffraction pattern. In this calculation, we used an in-silico model of insect flight muscle, which is known for its highly regular structure. We also extended this technique to an experimentally recorded muscle diffraction pattern.
The proteomic landscape and temporal dynamics of mammalian gastruloid development
Authors: Garge Riddhiman K. , Lynch Valerie , Fields Rose , Casadei Silvia , Best Sabrina , Stone Jeremy , Snyder Matthew , McGann Chris D. , Shendure Jay , Starita Lea M. , Hamazaki Nobuhiko , Schweppe Devin K. 
Published: September 2024

ABSTRACTGastrulation is the highly coordinated process by which the early embryo breaks symmetry, establishes germ layers and a body plan, and sets the stage for organogenesis. As early mammalian development is challenging to studyin vivo, stem cell-derived models have emerged as powerful surrogates,e.g.human and mouse gastruloids. However, although single cell RNA-seq (scRNA-seq) and high-resolution imaging have been extensively applied to characterize suchin vitroembryo models, a paucity of measurements of protein dynamics and regulation leaves a major gap in our understanding. Here, we sought to address this by applying quantitative proteomics to human and mouse gastruloids at four key stages of their differentiation (naïve ESCs, primed ESCs, early gastruloids, late gastruloids). To the resulting data, we perform network analysis to map the dynamics of expression of macromolecular protein complexes and biochemical pathways, including identifying cooperative proteins that associate with them. With matched RNA-seq and phosphosite data from these same stages, we investigate pathway-, stage- and species-specific aspects of translational and post-translational regulation,e.g.finding peri-gastrulation stages of human and mice to be discordant with respect to the mitochondrial transcriptome vs. proteome, and nominating novel kinase-substrate relationships based on phosphosite dynamics. Finally, we leverage correlated dynamics to identify conserved protein networks centered around congenital disease genes. Altogether, our data (https://gastruloid.brotmanbaty.org/) and analyses showcase the potential of intersectingin vitroembryo models and proteomics to advance our understanding of early mammalian development in ways not possible through transcriptomics alone.
A summary of intraspecific size variation for large odontocetes
Authors: McClure Joseph 
Published: September 2024

AbstractThe study of cetacean size and growth aids in research about their energetics, ecology, evolution, and taxonomy. Data on total body length and mass of large cetaceans is retained in an overwhelming amount of literature and previous reviews are limited in discussing the variation of both length and mass. Nearly all the known published literature was examined to provide a brief but comprehensive summary of the adult size of four large odontocetes. To supplement the existing literature, data from the International Whaling Commission catch database were reviewed and incorporated into analyses to improve descriptions of intraspecific variation in adult size forPhyseter macrocephalus. Regional comparisons of commercial data forP. macrocephalusrevealed apparent differences in adult size that are likely more attributable to catch biases rather than a diagnostic difference in size between populations.
Caveolin-1 and mechanical stress control the release of a pro-metastatic subpopulation of small extracellular vesicles
Authors: Saquel Cristian , Gracia Celine , Viaris de Lesegno Christine , Verweij Frederik , Urena-Martin Carlos , Raposo Graça , Lamaze Christophe 
Published: September 2024

AbstractExtracellular vesicles are lipid-enclosed vesicles released by most cells and are present in all human bodily fluids. EVs carry genetic material and proteins, which can be transferred to other cells, generating various biological effects. Caveolin-1 (Cav1) is a key structural protein of the small invaginations of the plasma membrane known as caveolae, which function as mechano-sensors and membrane tension buffering devices. Elevated levels of Cav1 have been detected in EVs from patients with advanced cancer. Given the importance of mechanical forces within the tumor microenvironment, we investigated the potential role of caveolae and Cav1 in regulating EV dynamics and cancer progression under mechanical stress. Our study revealed that different types of mechanical stress significantly induce the release of EVs from several cancer cell lines. These EVs were characterized as exosomes enriched for Cav1. Notably, we found that functional Cav1 was essential for the stress-induced increase in EV production. Lipidomic and proteomic analyses showed differences in the composition of EVs between WT and Cav1-deficient cells and between resting cells and cells subjected to mechanical stress. Additionally, EVs isolated from mechanically stressed cells were shown to promote enhanced migration and invasion of cancer cells in a Cav1-dependent manner. Altogether, our data uncover a new role for Cav1 in mediating cell-to-cell communication and promoting the acquisition of metastatic traits through the mechanical regulation of EV production and dynamics.
An antibiotic that mediates immune destruction of senescent cancer cells
Authors: Casagrande Raffi Gabriele , Chen Jian , Feng Xuezhao , Chen Zhen , Lieftink Cor , Deng Shuang , Mo Jinzhe , Zeng Chuting , Steur Marit , Wang Jing , Bleijerveld Onno B. , Hoekman Liesbeth , van der Wel Nicole , Wang Feng , Beijersbergen Roderick , Zheng Jian , Bernards Rene , Wang Liqin 
Published: September 2024

AbstractDrugs that eliminate senescent cells, senolytics, can be powerful when combined with pro-senescence cancer therapies. Using a CRISPR/Cas9-based genetic screen, we identify here SLC25A23 as a vulnerability of senescent cancer cells. Suppressing SLC25A23 disrupts cellular calcium homeostasis, impairs oxidative phosphorylation and interferes with redox signaling, leading to death of senescent cells. These effects can be replicated by salinomycin, a cation ionophore antibiotic. Salinomycin prompts a PANoptosis-like cell death in senescent cells, including apoptosis and two forms of immunogenic cell death: necroptosis and pyroptosis. Notably, we observed that salinomycin treatment or SLC25A23 suppression elevates reactive oxygen species, upregulating death receptor 5 via JNK pathway activation. We show that a combination of a DR5 agonistic antibody and salinomycin is a robust senolytic cocktail. We provide evidence that this drug combination provokes a potent NK and CD8+ T cell mediated immune destruction of senescent cancer cells, mediated by the pyroptotic cytokine IL18.SignificanceThe efficacy of multiple cancer drugs is limited by the induction of senescence, which enables cancer cells to evade cell death. We uncover here a new selective vulnerability of senescent cancer cells and we show that this vulnerability can be targeted with a commonly-used antibiotic. We show that a combination of senescence-inducing therapy, combined with this antibiotic causes a highly immunogenic cell death phenotype that further stimulates potent immune destruction of senescent cancer cells.