bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensive Single Cell Analysis Reveals Immune Cell Diversity among Healthy Individuals
Authors: Kashima Yukie , Kaneko Keiya , Reteng Patrick , Yoshitake Nina , Runtuwene Lucky Ronald , Nagasawa Satoi , Onishi Masaya , Seki Masahide , Suzuki Ayako , Sugano Sumio , Sakata-Yanagimoto Mamiko , Imai Yumiko , Nakayama-Hosoya Kaori , Kawana-Tachikawa Ai , Mizutani Taketoshi , Suzuki Yutaka 
Published: October 2021

ABSTRACTIt is believed that immune responses are different between individuals and at different times. In addition, personal health histories and unique environmental conditions should collectively determine the present state of immune cells. However, the cellular and molecular system mechanisms underlying such heterogeneity remain largely elusive. In this study, we conducted a systematic time-lapse single-cell analysis, using 171 single-cell libraries and 30 mass cytometry datasets intensively for seven healthy individuals. We found substantial diversity in immune cell populations and their gene expression patterns between different individuals. These patterns showed daily fluctuations even within the same individual spending a usual life. Similar diversities were also observed for the T cell receptor and B cell receptor repertoires. Detailed immune cell profiles at healthy statuses should give an essential background information to understand their immune responses, when the individual is exposed to various environmental conditions. To demonstrate this idea, we conducted the similar analysis for the same individuals on the vaccination of Influenza and SARS-CoV-2, since the date and the dose of the antigens are well-defined in these cases. In fact, we found that the distinct responses to vaccines between individuals, althougth key responses are common. Single cell immune cell profile data should make fundamental data resource to understand variable immune responses, which are unique to each individual.
Interleukin-1 is overexpressed in injured muscles following spinal cord injury and promotes neurogenic heterotopic ossification
Authors: Tseng Hsu-Wen , Kulina Irina , Girard Dorothée , Gueguen Jules , Vaquette Cedryck , Salga Marjorie , Fleming Whitney , Jose Beulah , Millard Susan M , Pettit Allison R , Schroder Kate , Thomas Gethin , Wheeler Lawrie , Genêt François , Banzet Sébastien , Alexander Kylie A , Levesque Jean-Pierre 
Published: October 2021

ABSTRACTNeurogenic heterotopic ossifications (NHOs) form in periarticular muscles following severe spinal cord (SCI) and traumatic brain injuries. The pathogenesis of NHO is poorly understood with no effective preventive treatment. The only curative treatment remains surgical resection of pathological NHOs. In a mouse model of SCI-induced NHO that involves a transection of the spinal cord combined with a muscle injury, a differential gene expression analysis revealed that genes involved in inflammation such as interleukin-1β (IL-1β) were overexpressed in muscles developing NHO. Using mice knocked-out for the gene encoding IL-1 receptor (IL1R1) and neutralizing antibodies for IL-1α and IL-1β, we show that IL-1 signaling contributes to NHO development following SCI in mice. Interestingly, other proteins involved in inflammation that were also overexpressed in muscles developing NHO, such as colony-stimulating factor-1, tumor necrosis factor or C-C chemokine ligand-2 did not promote NHO development. Finally using NHO biopsies from SCI and TBI patients, we show that IL-1β is expressed by CD68+ macrophages. IL-1α and IL-1β produced by activated human monocytes promote calcium mineralization of fibro-adipogenic progenitors isolated from muscles surrounding NHOs. Altogether these data suggest that interleukin-1 promotes NHO development in both humans and mice.
Single-molecule analysis of the entire perfringolysin O pore formation pathway
Authors: Guinness Conall Mc , Walsh James C. , Bayly-Jones Charles , Dunstone Michelle A. , Christie Michelle P. , Morton Craig J. , Parker Michael W. , Böcking Till 
Published: October 2021

AbstractThe cholesterol-dependent cytolysin perfringolysin O (PFO) is secreted by Clostridium perfringens as a bacterial virulence factor able to form giant ring-shaped pores that perforate and ultimately lyse mammalian cell membranes. To resolve the kinetics of all steps in the assembly pathway, we have used single-molecule fluorescence imaging to follow the dynamics of PFO on dye-loaded liposomes that lead to opening of a pore and release of the encapsulated dye. Formation of a long-lived membrane-bound PFO dimer nucleates the growth of an irreversible oligomer. The growing oligomer can insert into the membrane and open a pore at stoichiometries ranging from tetramers to full rings (∼35-mers), whereby the rate of insertion increases linearly with the number of subunits. Oligomers that insert before the ring is complete continue to grow by monomer addition post insertion. Overall, our observations suggest that PFO membrane insertion is kinetically controlled.
Facing the green threat: A waterflea’s defenses against a carnivorous plant
Authors: Kruppert Sebastian , Horstmann Martin , Weiss Linda C. , Barmaeva Elena , Kubitza Nadja , Poppinga Simon , Westermeier Anna S. , Speck Thomas , Tollrian Ralph 
Published: October 2021

AbstractWater fleas of the family Daphniidae are keystone species in many lentic ecosystems and, as most abundant filter feeders, link the primary production to higher trophic levels. As a response to the high predatory pressures, water fleas have evolved a range of defenses, including inducible defenses against animal predators. Here we show inCeriodaphnia dubiaa first example of such defenses induced by the presence of a coexisting plant predator, i.e. the carnivorous southern bladderwort (Utricularia australis, Lentibulariaceae), which possesses ultrafast underwater suction traps. When the bladderwort is present,C. dubiashows changes in morphology, life-history and behavior. While the morphological and behavioral adaptations improveC. dubia’ssurvival rate in the presence of this predator, the life-history parameters likely reflect trade-offs for the defense. Our study demonstrates plant-induced animal defenses, implying their potential relevance in freshwater ecosystems and contributing to an overall yet underestimated biodiversity of inducible defenses.Open Research StatementData is not finally prepared for upload yet. Once most fitting file types are determined and metadata is created we aim to upload all raw data as supporting information.
Activation of SGK1.1 up-regulates the M-current in the presence of epilepsy mutations
Authors: Martin-Batista Elva , Manville Rían W. , Rivero-Pérez Belinda , Bartolomé-Martín David , de la Rosa Diego Alvarez , Abbott Geoffrey W. , Giraldez Teresa 
Published: October 2021

ABSTRACTIn the central nervous system, the M-current plays a critical role in regulating subthreshold electrical excitability of neurons, determining their firing properties and responsiveness to synaptic input. The M-channel is mainly formed by subunits Kv7.2 and Kv7.3 that co-assemble to form a heterotetrametric channel. Mutations in Kv7.2 and Kv7.3 are associated with hyperexcitability phenotypes including benign familial neonatal epilepsy (BFNE) and neonatal epileptic encephalopathy (NEE). SGK1.1, the neuronal isoform of the serum and glucocorticoids-regulated kinase 1 (SGK1), increases M-current density in neurons, leading to reduced excitability and protection against seizures. Herein, using two-electrode voltage clamp on Xenopus laevis oocytes, we demonstrate that SGK1.1 selectively activates heteromeric Kv7 subunit combinations underlying the M-current. Importantly, activated SGK1.1 is able to up-regulate M-channel activity in the presence of two different epilepsy mutations found in Kv7.2 subunit, R207W and A306T. In addition, proximity ligation assays in the N2a cell line allowed us to address the effect of these mutations on Kv7-SGK1.1-Nedd4 molecular associations, a proposed pathway underlying M-channel up-regulation by SGK1.1
Pupil Dilation and Response Slowing Distinguish Deliberate Explorative Choices in the Probabilistic Learning Task
Authors: Kozunova Galina L. , Sayfulina Ksenia E. , Prokofyev Andrey O. , Medvedev Vladimir A. , Rytikova Anna M. , Stroganova Tatiana A. , Chernyshev Boris V. 
Published: October 2021

AbstractThis study examined whether pupil size and response time would distinguish directed exploration from random exploration and exploitation. Eighty-nine participants performed the two-choice probabilistic learning task while their pupil size and response time were continuously recorded. Using LMM analysis, we estimated differences in the pupil size and response time between the advantageous and disadvantageous choices as a function of learning success, i.e., whether or not a participant has learned the probabilistic contingency between choices and their outcomes. We proposed that before a true value of each choice became known to a decision-maker, both advantageous and disadvantageous choices represented a random exploration of the two options with an equally uncertain outcome, whereas the same choices after learning manifested exploitation and direct exploration strategies, respectively. We found that disadvantageous choices were associated with increases both in response time and pupil size, but only after the participants had learned the choice-reward contingencies. For the pupil size, this effect was strongly amplified for those disadvantageous choices that immediately followed gains as compared to losses in the preceding choice. Pupil size modulations were evident during the behavioral choice rather than during the pretrial baseline. These findings suggest that occasional disadvantageous choices, which violate the acquired internal utility model, represent directed exploration. This exploratory strategy shifts choice priorities in favor of information seeking and its autonomic and behavioral concomitants are mainly driven by the conflict between the behavioral plan of the intended exploratory choice and its strong alternative, which has already proven to be more rewarding.
An intranasally administrated SARS-CoV-2 beta variant subunit booster vaccine prevents beta variant viral replication in rhesus macaques
Authors: Sui Yongjun , Li Jianping , Andersen Hanne , Zhang Roushu , Prabhu Sunaina Kiran , Hoang Tanya , Venzon David , Cook Anthony , Brown Renita , Teow Elyse , Velasco Jason , Pessaint Laurent , Moore Ian N. , Lagenaur Laurel , Talton Jim , Breed Matthew W. , Kramer Josh , Bock Kevin W. , Minai Mahnaz , Nagata Bianca M. , Choo-Wosoba Hyoyoung , Lewis Mark G. , Wang Lai-Xi , Berzofsky Jay A. 
Published: October 2021

ABSTRACTEmerging of SARS-CoV-2 variants and waning of vaccine/infection-induced immunity poses threats to curbing the COVID-19 pandemic. An effective, safe, and convenient booster vaccine will be needed. We hypothesized that a variant-modified mucosal booster vaccine might induce local immunity to prevent SARS-CoV-2 infection at the port of entry. The beta-variant is hardest to cross-neutralize. Herein we assessed the protective efficacy of an intranasal booster composed of beta variant-spike protein S1 with IL-15 and TLR agonists in previously immunized macaques. The macaques were first vaccinated with Wuhan strain S1 with the same adjuvant. One year later, negligibly detectable SARS-CoV-2-specific antibody remained. Nevertheless, the booster induced vigorous humoral immunity including serum- and bronchoalveolar lavage (BAL)-IgG, secretory nasal- and BAL-IgA, and neutralizing antibody against the original strain and/or beta variant. Beta-variant S1-specifc CD4+and CD8+T cell responses were also elicited in PBMC and BAL. Following SARS-CoV-2 beta variant challenge, the vaccinated group demonstrated significant protection against viral replication in the upper and lower respiratory tracts, with almost full protection in the nasal cavity. The fact that one intranasal beta-variant booster administrated one year after the first vaccination provoked protective immunity against beta variant infections may inform future SARS-CoV-2 booster design and administration timing.
CombPDX: a unified statistical framework for evaluating drug synergism in patient-derived xenografts
Authors: Huang Licai , Wang Jing , Fang Bingliang , Meric-Bernstam Funda , Roth Jack A. , Ha Min Jin 
Published: October 2021

AbstractMotivationAnticancer combination therapy has been developed to increase efficacy by enhancing synergy. Patient-derived xenografts (PDXs) have emerged as reliable preclinical models to develop effective treatments in translational cancer research. However, in most PDX combination experiments, PDXs are tested on single dose levels and dose-response surface methods are not applicable for testing synergism.ResultsWe propose a comprehensive statistical framework to assess joint action of drug combinations from PDX tumor growth curve data. We provide various metrics and robust statistical inference procedures that locally (at a fixed time) and globally (across time) access combination effects under classical drug interaction models. Integrating genomic and pharmacological profiles in non-small-cell lung cancer (NSCLC), we have shown the utilities of combPDX in discovering effective therapeutic combinations and relevant biological mechanisms.AvailabilityWe provide an interactive web server, combPDX (https://licaih.shinyapps.io/CombPDX/), to analyze PDX tumor growth curve data and perform power analyses.ContactMJHa@mdanderson.orgSupplementary informationSupplementary data are available at Bioinformatics online.
Hysteresis in PIF4 and ELF3 dynamics dominates warm daytime memory in Arabidopsis
Authors: Murcia Germán , Nieto Cristina , Sellaro Romina , Prat Salomé , Casal Jorge J. 
Published: October 2021

AbstractPlants may experience large diurnal temperature fluctuations. Our knowledge of the molecular mechanisms of integration of these fluctuations and the resulting growth patterns is limited. Here we show that hypocotyl growth during the night responded not only to the current temperature but also to preceding daytime temperatures, revealing a memory of previous conditions. Daytime temperature affected the nuclear levels of PHYTOCHROME INTERACTING FACTOR 4 (PIF4) and LONG HYPOCOTYL 5 (HY5) during the next night. These jointly accounted for the observed growth kinetics, whereas memory of prior daytime temperature was impaired in thepif4andhy5mutants.PIF4promoter activity largely accounted for the temperature dependent changes in PIF4 protein levels. Noteworthy, the decrease inPIF4promoter activity triggered by cooling required a stronger temperature shift than the increase caused by warming. This hysteretic pattern required EARLY-FLOWERING 3 (ELF3). Warm temperatures promoted the formation of nuclear condensates of ELF3 in hypocotyl cells during the afternoon but not in the morning. These nuclear speckles showed poor sensitivity to subsequent cooling. We conclude that ELF3 achieves hysteresis and drives thePIF4promoter into the same behaviour, enabling a memory of daytime temperature conditions.
Spatial and temporal control of expression with light-gated LOV-LexA
Authors: Ribeiro Inês M.A. , Eßbauer Wolfgang , Kutlesa Romina , Borst Alexander 
Published: October 2021

AbstractThe ability to drive expression of exogenous genes in different tissues and cell types, under control of specific enhancers, has been crucial for discovery in biology. While many enhancers drive expression broadly, several genetic tricks were developed to obtain access to isolated cell types. Studies of spatially organized neuropiles in the central nervous system of insects have raised the need for a system that targets subsets of cells within a single neuron type, a feat currently dependent on stochastic flip-out methods. To access the same subsets of cells within a given expression pattern consistently across fruit flies, we developed the light-gated expression system LOV-LexA. We combined the bacterial LexA transcription factor with the plant-derived light oxygen voltage (LOV) photosensitive domain and a fluorescent protein. Exposure to blue light uncages a nuclear localizing signal in the C-terminal of the LOV domain, and leads to translocation of LOV-LexA to the nucleus, with subsequent initiation of transcription. LOV-LexA enables spatial and temporal control of expression of transgenes under LexAop sequences in larval fat body as well as pupal and adult neurons with blue light. The LOV-LexA tool is ready to use with GAL4 and Split-GAL4 drivers in its current form, and constitutes another layer of intersectional genetics, that provides light-controlled genetic access to specific subsets of cells across flies.
Sonic Hedgehog Pathway Modulation Normalizes Expression of Olig2 in Rostrally Patterned NPCs with Trisomy 21
Authors: Klein Jenny A. , Li Zhen , Rampam Sanjeev , Cardini Jack , Ayoub Amara , Shaw Patricia , Rachubinski Angela L. , Espinosa Joaquin M. , Zeldich Ella , Haydar Tarik F. 
Published: October 2021

SummaryThe intellectual disability found in people with Down syndrome (DS) is associated with a decrease in white matter in the central nervous system. To study the mechanism of this myelination deficit, we differentiated two isogenic lines of induced pluripotent stem cells (iPSCs) derived from people with DS into brain-like and spinal cord-like neural progenitor cells (NPCs) and promoted a transition towards oligodendroglial fate by activating the Sonic hedgehog (SHH) pathway. In the spinal cord-like trisomic cells, we found no difference in expression of OLIG2 or NKX2.2, two transcription factors essential for commitment to the oligodendrocyte (OL) lineage. However, in the brain-like trisomic NPCs, OLIG2 is significantly upregulated and is associated with reduced expression of NKX2.2. We found that this gene dysregulation and block in NPC transition can be normalized by increasing the concentration of a SHH pathway agonist (SAG) during differentiation. These results underscore the importance of regional and cell type differences in gene expression in DS and demonstrate that modulation of SHH signaling in trisomic cells can rescue an early perturbed step in neural lineage specification in DS.
S-Phase induced RNAs control ORC1 engagement to H2A.Z and firing of early DNA replication origins
Authors: Ummarino Simone , Poluben Larysa , Ebralidze Alex K. , Autiero Ida , Zhang Yhanzou , Paniza Theodore , Deshpande Madhura , Lee Johnathan , Bassal Mahmoud , Trinh Bon Q. , Balk Steven , Flaumenhaft Robert , Gerhardt Jeannine , Mirkin Sergei , Tenen Daniel G. , Di Ruscio Annalisa 
Published: October 2021

SummaryCoordinated initiation of DNA replication is essential to ensure efficient and timely DNA synthesis. Yet, the mechanism governing the “initiation” process in eukaryotic cells remains elusive. Here, we present data demonstrating a novel feature of RNAs transcribed in the proximity of actively replicating gene loci. We show that S-phAse-RNAs aNChoringORC1 (ANCORs) to the histone variant H2A.Z are licensors of the DNA replication process. The concomitant ANCOR-H2A.Z interaction is essential for the cells to initiate duplication of their genetic heritage. Widespread and locus-specific perturbations of these transcripts correlate with anomalous replication patterns and loss of the replicative marker at the origin site.Collectively, we unveil an RNA-mediated mechanism as the missing link for the generation of active replication origins and delineate a potential strategy to modulate replication in human cells at a local and global level.
Interspecific divergence of circadian properties in duckweed plants
Authors: Isoda Minako , Ito Shogo , Oyama Tokitaka 
Published: October 2021

SummaryThe circadian clock system is widely conserved in plants; however, divergence in circadian rhythm properties is poorly understood. We conducted a comparative analysis of the circadian properties of closely related duckweed species.Using a particle bombardment method, a circadian bioluminescent reporter was introduced into duckweed plants. We measured bioluminescence circadian rhythms of eight species of the genus Lemna and seven species of the genus Wolffiella at various temperatures (20, 25, and 30 °C) and light conditions (constant light or constant dark). Wolffiella species inhabit relatively warm areas and lack some tissues/organs found in Lemna species.Lemna species tended to show robust bioluminescence circadian rhythms under all conditions, while Wolffiella species showed lower rhythm stability, especially at higher temperatures. For Lemna, two species (L. valdiviana and L. minuta) forming a clade showed relatively lower circadian stability. For Wolffiella, two species (W. hyalina and W. repanda) forming a clade showed extremely long period lengths.The circadian properties of species primarily reflect their phylogenetic positions. The relationships between geographical and morphological factors and circadian properties are also suggested.
Effect of advertising spending on operating and market performance of banks: empirical evidence from Bangladesh
Authors: Molla Md. Ibrahim , Rahaman Md. Kayes Bin 
Published: October 2021

PurposeThe purpose of the paper is to empirically explore the economic effect of advertising spending on the performance of banks on a sample consisting of all banks listed on the Dhaka Stock Exchange over the period spanning from 2011 to 2019.Design/methodology/approachA dynamic panel data autoregressive approach of two-step system generalized method of moments (2-SGMM) estimation technique has been adopted in this study to analyze the contemporary and carryover effect of advertising on the financial performance of banks.FindingsThe findings indicate that advertising expenditure boosts banks' accounting returns but not their market value. Furthermore, advertising has a negative carryover effect on the financial performance of banks and is statistically significant for operating profit and return on equity. This finding demonstrates that the economic benefits of advertising expenditure lapse entirely within the current period and ought to be treated as an expense since it does not bring any future return for the banks in Bangladesh. In addition, this paper also offers no critical contrast between the impact of advertising spending on the performance of both conventional and Islamic banks operating in Bangladesh.Originality/valueTo the best of the authors' knowledge, no study so far has looked into the effect of advertising on the profitability and the market value of the banks operating in Bangladesh, and this is the first study that explores this relationship.