bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repetitive Sulfur Dioxide Exposure in Mice Models Post-Deployment Respiratory Syndrome
Authors: Gutor Sergey S. , Salinas Rodrigo I. , Nichols David S. , Bazzano Julia M. R. , Han Wei , Gokey Jason J. , Vasiukov Georgii , West James D. , Newcomb Dawn C. , Dikalova Anna E. , Richmond Bradley W. , Dikalov Sergey I. , Blackwell Timothy S. , Polosukhin Vasiliy V. 
Published: May 2023

AbstractSoldiers deployed to Iraq and Afghanistan have a higher prevalence of respiratory symptoms than non-deployed military personnel and some have been shown to have a constellation of findings on lung biopsy termed post-deployment respiratory syndrome (PDRS). Since many of the deployers in this cohort reported exposure to sulfur dioxide (SO2), we developed a model of repetitive exposure to SO2in mice that phenocopies many aspects of PDRS, including adaptive immune activation, airway wall remodeling, and pulmonary vascular disease (PVD). Although abnormalities in small airways were not sufficient to alter lung mechanics, PVD was associated with the development of pulmonary hypertension and reduced exercise tolerance in SO2exposed mice. Further, we used pharmacologic and genetic approaches to demonstrate a critical role for oxidative stress and isolevuglandins in mediating PVD in this model. In summary, our results indicate that repetitive SO2exposure recapitulates many aspects of PDRS and that oxidative stress may mediate PVD in this model, which may be helpful for future mechanistic studies examining the relationship between inhaled irritants, PVD, and PDRS.
Senescent cells and macrophages cooperate through a multi-kinase signaling network to promote intestinal transformation in Drosophila
Authors: Datta Ishwaree , Bangi Erdem 
Published: May 2023

ABSTRACTCellular senescence is a conserved biological process essential for embryonic development, tissue remodeling, repair, and a key regulator of aging. Senescence also plays a crucial role in cancer, though this role can be tumor-suppressive or tumor-promoting, depending on the genetic context and the microenvironment. The highly heterogeneous, dynamic, and context-dependent nature of senescence-associated features and the relatively small numbers of senescent cells in tissues makesin vivomechanistic studies of senescence challenging. As a result, which senescence-associated features are observed in which disease contexts and how they contribute to disease phenotypes remain largely unknown. Similarly, the specific mechanisms by which various senescence-inducing signals are integratedin vivoto induce senescence and why some cells become senescent while their immediate neighbors do not are unclear. Here, we identify a small number of cells that exhibit multiple features of senescence in a genetically complex model of intestinal transformation we recently established in the developing Drosophila larval hindgut epithelium. We demonstrate that these cells emerge in response to concurrent activation of AKT, JNK, and DNA damage response pathways within transformed tissue. Eliminating senescent cells, genetically or by treatment with senolytic compounds, reduces overgrowth and improves survival. We find that this tumor-promoting role is mediated by Drosophila macrophages recruited to the transformed tissue by senescent cells, which results in non-autonomous activation of JNK signaling within the transformed epithelium. These findings emphasize complex cell-cell interactions underlying epithelial transformation and identify senescent cell-macrophage interactions as a potential druggable node in cancer.One sentence summary:Interactions between transformed senescent cells and macrophages drive tumorigenesis.
The Role of the Eyes: Investigating Face Cognition Mechanisms Using Machine Learning and Partial Face Stimuli
Authors: Chanpornpakdi Ingon , Tanaka Toshihisa 
Published: May 2023

ABSTRACTFace cognition plays a significant role in social interaction. The typical stimulus used to study face cognition mechanisms is a rapid serial visual presentation (RSVP). During the RSVP task, the brain response called event-related potential (ERP) is evoked when a person recognizes a target image. Many trials are required to average and obtain a clean ERP to interpret the cognitive mechanism behind the ERP response. However, increasing the trial number can cause fatigue and affect evoked ERP amplitude. This paper adopts a different perspective; machine learning might extract a meaningful cognitive result that reveals the face cognition mechanism without directly focusing on the characteristic of the ERP. We implemented an xDAWN covariance matrix method to enhance the data quality and a support vector machine classification model to predict the participant’s event of interest using ERP components evoked in the partial face cognition task. The effect of face components and the physical response was also investigated to explore the role of each component and find the possibility of reducing fatigue caused during the experiment. We found that the eyes were the most effective component. Similar statistical results were obtained from full face and partial face with eyes visible in both behavioral response and classification performance. From these results, the eye component could be the most crucial in face cognition. So, there could be some similarities in the face cognition mechanism of the full face and the partial face with eyes visible, which should be further investigated using ERP characteristics.
On the results of causal optogenetic engram manipulations
Authors: Jou Claudia , Hurtado José R. , Carrillo-Segura Simon , Park Eun Hye , Fenton André A. 
Published: May 2023

SUMMARYCellular-resolution manipulation technologies like optogenetics enable so-called causal engram-cell experiments in which learning-activated neurons are tagged with a light-responsive protein (opsin) such that subsequent photostimulation elicits memory behavior. The opsin-tagged neurons are considered key neural circuit elements with photostimulation demonstrating their sufficiency for memory expression. Can the sufficiency interpretation be correct if the brain is a complex dynamical system with adaptive, non-linear, and homeostatic interactions? We find that during photostimulation of place avoidance memory-tagged neurons, mouse CA1 hippocampus activity maintains intrinsic ensemble discharge relationships and the low-dimensional manifold organization of the population dynamics. Although the photostimulation causes spatially-precise conditioned avoidance, such manipulations, are better interpreted as eliciting the endogenous population dynamics of a complex system, rather than the causal demonstration of neural circuit function.
Interruption of the Intratumor CD8:Treg Crosstalk Improves the Efficacy of PD-1 Immunotherapy
Authors: Geels Shannon N , Moshensky Alexander , Sousa Rachel S , Walker Benjamin L , Singh Rima , Gutierrez Giselle , Hwang Michael , Mempel Thorsten R , Nie Qing , Othy Shivashankar , Marangoni Francesco 
Published: May 2023

SUMMARYPD-1 blockade unleashes the potent antitumor activity of CD8 cells but can also promote immunosuppressive T regulatory (Treg) cells, which may worsen response to immunotherapy. Tumor Treg inhibition is a promising strategy to overcome therapeutic resistance; however, the mechanisms supporting tumor Tregs during PD-1 immunotherapy are largely unexplored. Here, we report that PD-1 blockade increases tumor Tregs in mouse models of immunogenic tumors, including melanoma, and metastatic melanoma patients. Unexpectedly, Treg accumulation was not caused by Treg-intrinsic inhibition of PD-1 signaling but instead depended on an indirect effect of activated CD8 cells. CD8 cells colocalized with Tregs within tumors and produced IL-2, especially after PD-1 immunotherapy. IL-2 upregulated the anti-apoptotic protein ICOS on tumor Tregs, causing their accumulation. ICOS signaling inhibition before PD-1 immunotherapy resulted in increased control of immunogenic melanoma. Thus, interrupting the intratumor CD8:Treg crosstalk is a novel strategy that may enhance the efficacy of immunotherapy in patients.
Monitoring and maturation of cardiomyocyte differentiated from human induced pluripotent stem cells using a multi-functional tissue engineering platform
Authors: Kim A-Ri , Shrivastava Sajal , Lee Han-Byeol , Lee Nae-Eung 
Published: May 2023

AbstractBackgroundThe use of human induced pluripotent stem cells (hiPSCs) is attracting attention as a potential personalized therapy for damaged myocardium, as they are accessible and compatible with the human body. The hiPSCs can be effectively differentiated into cardiomyocytes (CMs), which are essential for myocardial regeneration. However, current approaches have been unable to fully replicate the electro-mechanical functions of natural CMs.MethodsAlthough several methods have been used to stimulate hiPSC-CMs for maturation, the ability to integrate multiple stimuli that influence myocardial cell function has been limited. To address this challenge, we have developed a multi-functional tissue engineering system for CMs that is based on a stretchable multielectrode array (SMEA). The SMEA is housed in a mini-incubator and is stretchable, durable and autoclavable.ResultsThe system can independently control co-stimulation parameters of electrical and mechanical stimuli simultaneously. Furthermore, the system can monitor the status of the cells throughout their proliferation and differentiation of hiPSCs, as well as the stimulation of hiPSC-CMs, through electrochemical cell impedance spectroscopy. By applying co-stimulation, we have observed the enhanced maturation of hiPSC-CMs.ConclusionsOur innovative system holds great potential as a tool for improving the culture and engineering of electrogenic cells with enhanced maturity.
Why Na+ has higher propensity than K+ to condense DNA in a crowded environment
Authors: Kolesnikov Egor S. , Gushchin Ivan Yu. , Zhilyaev Peter A. , Onufriev Alexey V. 
Published: May 2023

AbstractExperimentally, in the presence of crowding agent polyethylene glycol (PEG), sodium ions compact double-stranded DNA more readily than potassium ions. Here we have used molecular dynamics simulations and the “ion binding shells model” of DNA condensation to provide an atomic level picture that explains the observed variations in condensation of short (25 base pairs) DNA duplexes in solutions containing different monovalent cations and PEG; several predictions are made. In general, there are two major modes (shells) of ion binding to DNA, internal and external, distinguished by the proximity of bound ions to the helical axis. Externally bound ions contribute the most to the ion-induced aggregation of DNA duplexes. The simulations reveal that for two adjacent DNA duplexes, as well as for a single DNA duplex, the number of externally bound Na+ions is larger than the number of K+ions over a wide range of NaCl and KCl concentrations in the presence of PEG, providing a qualitative explanation for the higher propensity of sodium ions to compact DNA under crowded conditions. The qualitative picture is confirmed by an estimate of the corresponding free energy of DNA aggregation in the presence of different ions: the aggregation free energy is at least 0.2kBTper base pair more favorable in solution with NaCl than with KCl, at the same ion concentration. The estimated attraction free energy of DNA duplexes in the presence of Na+depends on the DNA sequence noticeably: we predict that AT-rich DNA duplexes are more readily condensed than GC-rich ones in the presence of Na+. The sequence dependence of the DNA aggregation propensity is nearly absent for K+. Counter-intuitively, the addition of a small amount of crowding agent with high affinity for the specific condensing ion may lead to the weakening of the ion-mediated DNA-DNA attraction, shifting the equilibrium away from the DNA condensed phase.
Health system intervention packages on improving coverage of kangaroo mother care for preterm or LBW infants: a mixed-methods systematic review
Authors: Bergman Nils , Talej Megan , Smith Emily R. , Rao Suman PN , Gupta Shuchita 
Published: May 2023

ABSTRACTIntroductionGlobal coverage of Kangaroo mother care (KMC) remains low and health system intervention strategies that may improve coverage are not known.MethodsWe conducted a systematic review of studies evaluating the effect of health system intervention strategies for KMC implementation compared to no or different interventions, on KMC coverage in preterm or LBW infants. KMC coverage achieved by various studies was summarized. All included studies were classified as those that achieved increased KMC coverage (defined as ≥25% increase from baseline, with final coverage ≥50%) or low KMC coverage (defined as <25% increase from baseline or final coverage <50%). Studies that achieved increased KMC coverage were further classified based on the mean duration of skin-to-skin contact (SSC; hours per day) achieved. Health system interventions in different categories were summarized by WHO health system building blocks to understand factors linked to increased KMC coverage.FindingsWe identified 16 studies evaluating 15 health system intervention packages for KMC implementation that applied interventions in one or more health system building blocks that reported KMC coverage. All three studies that applied interventions across 5-6 building blocks (100%), two of the four studies that applied interventions across 3-4 building blocks (50%), and three of the nine studies that applied interventions across 1-2 building blocks (33%), achieved increased KMC coverage. Studies that did not achieve increased coverage had interventions primarily targeting health workforce and service delivery and were weak on leadership and governance, financing, and health information systems. All three studies that achieved increased KMC coverage with mean SSC ≥8h/d (100%), three of the five studies that achieved increased KMC coverage with mean SSC <8h/d (60%), and three of the eight studies with low KMC coverage (38%) had high-intensity interventions in at least one health system building blocks. High-level leadership engagement, KMC supportive policies, staff licensing, and facility standards regulations, strengthened numbers and capacity of nursing staff, government funding and expanded health insurance, wards with conducive environment, and recording KMC-specific indicators in clinical registers were key factors among studies that achieved increased KMC coverage.ConclusionHigh-intensity interventions across multiple health system building blocks should be used for equitable scale-up of KMC.
RealSeq2: a software integrated with UMI identification, error correction, and methylation modifications storing
Authors: Wang Ke , Song Mengmeng , Li Min , Cui Tianyu , Liu Zhentian , Yu Enjie , Fang Huan , Gao Xuan , Xia Xuefeng , Wang Jiayin , Guan Yanfang , Liu Tao , Yi Xin 
Published: May 2023

AbstractHigh-throughput UMI technology sequencing is widely used in early tumor screening, detection, recurrence monitoring, etc. Detecting extremely low-frequency mutations is especially important for monitoring tumor recurrence, so high-precision data, as well as high-quality data, are required. We developedRealSeq2, a new integrated data-preprocessing software based on fastp and gencore, to achieve adapter removal, quality control, UMI identification, and generate consensus reads by clustering and error correction using multithreading in high-throughput next-generation sequencing background.RealSeq2also supports methylation data of 5-methylcytosine bisulfite-free sequencing.RealSeq2defined a new tag in SAM for storing methylation information, which is beneficial for co-identifying methylation sites and mutation sites for downstream analysis.RealSeq2includes three submodules: ReadsProfiler, ReadsCleaner, and ReadsRecycler. In addition, the output format file (BAM or SAM) is universal for downstream analyses.RealSeq2is the preferred upstream analysis software for the co-detection of ultra-low frequency mutations and bisulfite-free methylation data. The error profile provides data support for downstream analysis. Additionally, XM tags will become a standard protocol for recording methylation signals.
A central helical hairpin in SPD-5 enables centrosome strength and assembly
Authors: Rios Manolo U. , Ryder Bryan D. , Familiari Nicole , Joachimiak Łukasz A. , Woodruff Jeffrey B. 
Published: May 2023

ABSTRACTCentrosomes organize microtubules for mitotic spindle assembly and positioning. Forces mediated by these microtubules create tensile stresses on pericentriolar material (PCM), the outermost layer of centrosomes. How PCM resists these stresses is unclear at the molecular level. Here, we use cross-linking mass spectrometry (XL-MS) to map interactions underlying multimerization of SPD-5, an essential PCM scaffold component inC. elegans. We identified an interaction hotspot in an alpha helical hairpin motif in SPD-5 (a.a. 541-677). XL-MS data,ab initiostructural predictions, and mass photometry suggest that this region dimerizes to form a tetrameric coiled-coil. Mutating a helical section (a.a. 610-640) or a single residue (R592) inhibited PCM assembly in embryos. This phenotype was rescued by eliminating microtubule pulling forces, revealing that PCM assembly and material strength are interrelated. We propose that interactions mediated by the helical hairpin strongly bond SPD-5 molecules to each other, thus enabling PCM to assemble fully and withstand stresses generated by microtubules.
Minmers are a generalization of minimizers that enable unbiased local Jaccard estimation
Authors: Kille Bryce , Garrison Erik , Treangen Todd J , Phillippy Adam M 
Published: May 2023

1AbstractsMotivationThe Jaccard similarity onk-mer sets has shown to be a convenient proxy for sequence identity. By avoiding expensive base-level alignments and comparing reduced sequence representations, tools such as MashMap can scale to massive numbers of pairwise comparisons while still providing useful similarity estimates. However, due to their reliance on minimizer winnowing, previous versions of MashMap were shown to be biased and inconsistent estimators of Jaccard similarity. This directly impacts downstream tools that rely on the accuracy of these estimates.ResultsTo address this, we propose theminmerwinnowing scheme, which generalizes the minimizer scheme by use of a rolling minhash with multiple sampledk-mers per window. We show both theoretically and empirically that minmers yield an unbiased estimator of local Jaccard similarity, and we implement this scheme in an updated version of MashMap. The minmer-based implementation is over 10 times faster than the minimizer-based version under the default ANI threshold, making it well-suited for large-scale comparative genomics applications.AvailabilityMashMap3 is available athttps://github.com/marbl/MashMapContactblk6@rice.edu,adam.phillippy@nih.gov
Measuring sub-nanometer fluctuations at microsecond temporal resolution with metal-and graphene-induced energy transfer spectroscopy
Authors: Chen Tao , Karedla Narain , Enderlein Jörg 
Published: May 2023

AbstractOut-of-plane fluctuations, also known as stochastic displacements, of biological membranes play a crucial role in regulating many essential life processes within cells and organelles. Despite the availability of various methods for quantifying membrane dynamics, accurately quantifying complex membrane systems with rapid and tiny fluctuations, such as mitochondria, remains a challenge. In this work, we present a novel methodology that combines metal/graphene-induced energy transfer (MIET/GIET) with fluorescence correlation spectroscopy (FCS) to quantify out-of-plane fluctuations of membranes with simultaneous spatiotem-poral resolution of approximately one nanometer and one microsecond that is unprecedented.To validate the technique and spatiotemporal resolution, we measured bending undulations of model membranes. Furthermore, we demonstrate the versatility and applicability of MIET/GIET-FCS for studying diverse membrane systems, including the widely studied fluctuating membrane system of human red blood cells, as well as two unexplored membrane systems with tiny fluctuations, a pore-spanning membrane, and mitochondrial inner/outer membranes.
Apical-driven cell sorting optimised for tissue geometry ensures robust patterning
Authors: Moghe Prachiti , Belousov Roman , Ichikawa Takafumi , Iwatani Chizuru , Tsukiyama Tomoyuki , Graner François , Erzberger Anna , Hiiragi Takashi 
Published: May 2023

ABSTRACTTissue patterning coordinates morphogenesis, cell dynamics and fate specification. Understanding how these processes are coupled to achieve precision despite their inherent variability remains a challenge. Here, we investigate how salt-and-pepper epiblast and primitive endoderm (PrE) cells sort and robustly pattern the inner cell mass (ICM) of mammalian blastocysts. Quantifying cellular dynamics and mechanics together with simulations show a key role for the autonomously acquired apical polarity of mouse PrE cells in coupling cell fate and dynamics in tissue contexts. Specifically, apical polarity forms actin protrusions and is required for Rac1-dependent migration towards the ICM surface, where PrE cells are trapped due to decreased tension at their apical domain, while depositing an extracellular matrix gradient, breaking the tissue-level symmetry and collectively guiding their own migration. Tissue size perturbations and comparison with monkey blastocysts further demonstrate that the fixed proportion of PrE/epiblast cells is optimal and robust to variability in embryo size.
A chromosome-level reference genome for the common octopus,Octopus vulgaris(Cuvier, 1797)
Authors: Destanović Dalila , Schultz Darrin T. , Styfhals Ruth , Cruz Fernando , Gómez-Garrido Jèssica , Gut Marta , Gut Ivo , Fiorito Graziano , Simakov Oleg , Alioto Tyler S. , Ponte Giovanna , Seuntjens Eve 
Published: May 2023

AbstractCephalopods are emerging animal models and include iconic species for studying the link between genomic innovations and physiological and behavioral complexities. Coleoid cephalopods possess the largest nervous system among invertebrates, both for cell counts and brain-to-body ratio.Octopus vulgarishas been at the center of a long-standing tradition of research into diverse aspects of cephalopod biology, including behavioral and neural plasticity, learning and memory recall, regeneration, and sophisticated cognition. However, no chromosome-scale genome assembly is available forO. vulgaristo aid in functional studies. To fill this gap, we sequenced and assembled a chromosome-scale genome of the common octopus,O. vulgaris. The final assembly spans 2.8 billion basepairs, 99.34% of which are in 30 chromosome-scale scaffolds. Hi-C heatmaps support a karyotype of 1n=30 chromosomes. Comparisons with other octopus species’ genomes show a conserved octopus karyotype, and a pattern of local genome rearrangements between species. This new chromosome-scale genome ofO. vulgariswill further facilitate research in all aspects of cephalopod biology, including various forms of plasticity and the neural machinery underlying sophisticated cognition, as well as an understanding of cephalopod evolution.