bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep spindles track cortical learning patterns for memory consolidation
Authors: Petzka Marit , Chatburn Alex , Charest Ian , Balanos George M. , Staresina Bernhard P. 
Published: September 2021

AbstractMemory consolidation, the transformation of labile memory traces into stable long-term representations, is facilitated by post-learning sleep. Computational and biophysical models suggest that sleep spindles may play a key mechanistic role for consolidation, igniting structural changes at cortical sites involved in prior learning. Here we tested the resulting prediction that spindles are most pronounced over learning-related cortical areas and that the extent of this learning-spindle overlap predicts behavioural measures of memory consolidation. Using high-density scalp Electroencephalography (EEG) and Polysomnography (PSG) in healthy volunteers, we first identified cortical areas engaged during a temporospatial associative memory task (power decreases in the alpha/beta frequency range, 6-20 Hz). Critically, we found that participant-specific topographies (i.e., spatial distributions) of post-learning sleep spindle amplitude correlated with participant-specific learning topographies. Importantly, the extent to which spindles tracked learning patterns further predicted memory consolidation across participants. Our results provide empirical evidence for a role of post-learning sleep spindles in tracking learning networks, thereby facilitating memory consolidation.
Multiplex spatial systems analysis of local nanodose drug responses predicts effective treatment combinations of immunotherapies and targeted agents in mammary carcinoma
Authors: Tatarova Zuzana , Blumberg Dylan C. , Korkola James E. , Heiser Laura M. , Muschler John L. , Schedin Pepper J. , Ahn Sebastian W. , Mills Gordon B. , Coussens Lisa M. , Jonas Oliver , Gray Joe W. 
Published: September 2021

SUMMARYBetter methods are needed to identify effective combinations of immunotherapies with chemotherapies and targeted anti-cancer agents. Here we present a Multiplex Implantable Microdevice Assay (MIMA) system for rapid in vivo assessment of the effects of multiple, spatially separate anticancer drugs directly in the complex tumor microenvironment. In prototypic experiments, olaparib, lenvatinib, palbociclib, venetoclax, panobinostat, doxorubicin, and paclitaxel and combinations thereof were administered simultaneously to murine mammary tumor models. Quantitative multiplex immunohistochemistry and spatial systems analyses of each local drug response defined cellular relations of fibroblasts, endothelial cells, immune lineages, immunogenic cell death, tumor proliferation and/or cancer stem cells that were used to predict effective drug combinations. A predicted combination of panobinostat, venetoclax and anti-CD40 showed long-term anti-tumor efficacy in multiple mouse models with no observable toxicity when administered systemically. Future MIMA use promises to design effective drug combinations for tumor cell control and immune activation on a personalized basis.
Nanomolar, noncovalent antagonism of hedgehog cholesterolysis: exception to the “irreversibility rule” for protein autoprocessing inhibition
Authors: Wagner Andrew G , Stagnitta Robert T , Xu Zihan , Pezzullo John L , Kandel Nabin , Giner José-Luis , Covey Douglas F , Wang Chunyu , Callahan Brian P 
Published: September 2021

ABSTRACTHedgehog (Hh) signaling ligands undergo carboxy terminal sterylation through specialized autoprocessing, called cholesterolysis. Sterylation is brought about intramolecularly in a single turn-over by an enzymatic domain, called HhC. HhC is found in precursor Hh proteins only. Through cholesterolysis, HhC is cleaved from the precursor. Attempts to identify molecules that inhibit intramolecular cleavage/sterylation activity of HhC have resulted in antagonists that bind HhC irreversibly through covalent mechanisms, as is commonplace for protein autoprocessing inhibitors. Here we report an exception to the “irreversibility rule” for protein autoprocessing inhibition. Using a FRET-based activity assay for HhC, we screened a focused library of sterol-like analogs for HhC cholesterolysis inhibitors. We identified and validated four structurally related noncovalent inhibitors, which were then used for SAR studies. The most effective derivative, tBT-HBT, binds HhC reversibly with an IC50 of 300 nM. An allosteric binding site for tBT-HBT, encompassing interactions from the two subdomains of HhC, is suggested by kinetic analysis, mutagenesis studies, and photoaffinity labeling. A striking resemblance is found between the inhibitors described here and a family of noncovalent, allosteric activators of HhC, which we described previously. The inhibitor/activator duality appears to be mediated by the same allosteric site, which displays sensitivity to subtle differences in the structure of a heterocycle substituent on the effector molecule.
Molecular Organization of the Early Stages of Nucleosome Phase Separation Visualized by Cryo-Electron Tomography
Authors: Zhang Meng , Díaz-Celis César , Onoa Bibiana , Cañari-Chumpitaz Cristhian , Requejo Katherinne I. , Liu Jianfang , Vien Michael , Nogales Eva , Ren Gang , Bustamante Carlos 
Published: September 2021

SummaryIt has been proposed that the intrinsic property of nucleosome arrays to undergo liquid-liquid phase separation (LLPS) in vitro is responsible for chromatin domain organization in vivo. However, understanding nucleosomal LLPS has been hindered by the challenge to characterize the structure of resulting heterogeneous condensates. We used cryo-electron tomography and deep learning-based 3D reconstruction/segmentation to determine the molecular organization of condensates at various stages of LLPS. We show that nucleosomal LLPS involves a two-step process: a spinodal decomposition process yielding irregular condensates, followed by their unfavorable conversion into more compact, spherical nuclei that grow into larger spherical aggregates through accretion of spinodal material or by fusion with other spherical condensates. Histone H1 catalyzes more than 10-fold the spinodal-to-spherical conversion. We propose that this transition involves exposure of nucleosome hydrophobic surfaces resulting in modified inter-nucleosome interactions. These results suggest a physical mechanism by which chromatin may transition from interphase to metaphase structures.
The eyes have it: The pupillary light response as a physiological index of aphantasia, sensory and phenomenological imagery strength
Authors: Kay Lachlan , Keogh Rebecca , Andrillion Thomas , Pearson Joel 
Published: September 2021

AbstractThe pupillary light response is an important automatic physiological response that optimises light reaching the retina. Recent work has shown that the pupil also adjusts in response to illusory brightness and a range of cognitive functions, however, it remains unclear what exactly drives these endogenous changes. Here we show that the imagery pupillary light response correlates with objective measures of sensory imagery strength. Further, the trial-by-trial phenomenological vividness of visual imagery is tracked by the imagery pupillary light response. We also demonstrated that there was no evidence for an imagery pupillary light response in a group of individuals without visual imagery (aphantasia), however, they did show perceptual pupil light responses and pupil dilation with larger cognitive load. Our results provide evidence that the pupillary light response indexes the sensory strength of visual imagery and also provides the first physiological validation of aphantasia.
Genomic Signatures of Sexual Selection on Pollen-Expressed Genes in Arabis alpina
Authors: Gutiérrez-Valencia Juanita , Fracassetti Marco , Horvath Robert , Laenen Benjamin , Désamore Aurélie , Drouzas Andreas D. , Friberg Magne , Kolář Filip , Slotte Tanja 
Published: September 2021

AbstractFertilization in angiosperms involves the germination of pollen on the stigma, followed by the extrusion of a pollen tube that elongates through the style and delivers two sperm cells to the embryo sac. Sexual selection could occur throughout this process when male gametophytes compete for fertilization. The strength of sexual selection during pollen competition should be affected by the number of genotypes deposited on the stigma. As increased self-fertilization reduces the number of mating partners, and the genetic diversity and heterozygosity of populations, it should thereby reduce the intensity of sexual selection during pollen competition. Despite the prevalence of mating system shifts, few studies have directly compared the molecular signatures of sexual selection during pollen competition in populations with different mating systems. Here we analyzed whole-genome sequences from natural populations of Arabis alpina, a species showing mating system variation across its distribution, to test whether shifts from cross- to self-fertilization result in molecular signatures consistent with sexual selection on genes involved in pollen competition. We found evidence for efficient purifying selection on genes expressed in vegetative pollen, and overall weaker selection on sperm-expressed genes. This pattern was robust when controlling for gene expression level and specificity. In agreement with the expectation that sexual selection intensifies under cross-fertilization, we found that the efficacy of purifying selection on male gametophyte-expressed genes was significantly stronger in genetically more diverse and outbred populations. Our results show that intra-sexual competition shapes the evolution of pollen-expressed genes, and that its strength fades with increasing self-fertilization rates.
Three-dimensional Super-resolved Imaging of Paraffin-embedded Kidney Samples
Authors: Unnersjö-Jess David , Ramdedovic Amer , Höhne Martin , Butt Linus , Koehler Felix C. , Müller Roman-Ulrich , Hoyer Peter F. , Blom Hans , Schermer Bernhard , Benzing Thomas 
Published: September 2021

ABSTRACTDiseases of the glomeruli, the renal filtration units, are a leading cause of progressive kidney disease. Assessment of the ultrastructure of podocytes at the glomerular filtration barrier is essential for diagnosing diverse disease entities, providing insight into the disease pathogenesis as well as monitoring treatment responses. New technologies, including superresolved nanoscopy and expansion microscopy, as well as new sample preparation techniques, are starting to revolutionize imaging of biopsy specimens. However, our previous approaches for simple and fast three-dimensional imaging of optically cleared samples are to date not compatible with formalin fixed paraffin-embedded (FFPE) tissue, impeding application in clinical routine. Here we provide protocols that circumvent these limitations and allow for three dimensional STED and confocal imaging of FFPE kidney tissue with similar staining and image quality as compared to our previous approaches. This would increase the feasibility to implement these protocols in clinical routines, as FFPE is the gold standard method for storage of patient samples.
Distinct neutralizing kinetics and magnitudes elicited by different SARS-CoV-2 variant spikes
Authors: Liu Yang , Liu Jianying , Zou Jing , Ren Ping , Weaver Scott C. , Xie Xuping , Shi Pei-Yong 
Published: September 2021

AbstractThe rapid evolution of SARS-CoV-2 mandates a better understanding of cross-protection between variants after vaccination or infection, but studies directly evaluating such cross-protection are lacking. Here we report that immunization with different variant spikes elicits distinct neutralizing kinetics and magnitudes against other SARS-CoV-2 variants. After immunizing hamsters with wild-type or mutant SARS-CoV-2 bearing variant spikes from Alpha, Beta, Gamma, or Epsilon, the animals developed faster and greater neutralization activities against homologous SARS-CoV-2 variants than heterologous variants, including Delta. The rank of neutralizing titers against different heterologous variants varied, depending on the immunized variant spikes. The differences in neutralizing titers between homologous and heterologous variants were as large as 62-, 15-, and 9.7-fold at days 14, 28, and 45 post-immunization, respectively. Nevertheless, all immunized hamsters were protected from challenges with all SARS-CoV-2 variants, including those exhibiting the lowest neutralizing antibody titers. The results provide insights into the COVID-19 vaccine booster strategies.
FGFR3 activating mutations induce luminal-like papillary bladder tumor formation and favor a male gender bias
Authors: Shi Ming-Jun , Moreno-Vega Aura , Fontugne Jacqueline , Meng Xiang-Yu , Dufour Florent , Kamoun Aurélie , Lindskrog Sia Viborg , Rapinat Audrey , Dunois-Larde Claire , Lepage May-Linda , Chapeaublanc Elodie , Levrel Olivier , Lebret Thierry , Almeida Anna , De Reynies Aurélien , Dyrskjøt Lars , Allory Yves , Radvanyi François , Bernard-Pierrot Isabelle 
Published: September 2021

AbstractBackgroundFGFR3 mutations are among the most frequent genetic alterations in bladder cancer and are enriched in the luminal papillary subtype of muscle-invasive tumors (MIBC) and luminal-like classes 1 and 3 of non-MIBC. To study their oncogenic propertiesin vivo, we developed here a genetically engineered mouse (GEM) model expressing the most frequent FGFR3 mutation, FGFR3-S249C, in urothelial cells.MethodsBladder tumorigenesis was monitored in FGFR3-S249C mice. FGFR3 expression was assessed by RT-qPCR in the transgenic mice urothelium and in various human epithelia. Transcriptomic data were obtained from mouse bladder tumors and crossspecies comparisons were performed. Sex bias in FGFR3-mutated tumors was evaluated in our GEM model and in the TCGA and UROMOL cohorts of patients including 408 MIBC and 419 NMIBC, respectively. The association of androgen receptor (AR) activity, based on the expression of its target genes, with FGFR3 mutations was examined in these two cohorts. Binding of AR to its response element and AR phosphorylation in FGFR3-dependent cell lines were evaluated.ResultsFGFR3-S249C expression in the urothelium of mice induced spontaneous low-grade papillary bladder tumors resembling the human counterpart at the histological and transcriptomic levels. Mutant-FGFR3 expression levels impacted tumor formation incidence in mice and mutant-FGFR3-driven human tumors were restricted to epithelia presenting high normal expression levels of FGFR3. The known bladder cancer male gender bias, also found in our model, was even higher in human FGFR3-mutated compared to wild-type tumors and associated with a higher AR regulon activity considering gender adjustment. AR phosphorylation and regulon activity were modulated by FGFR3 in FGFR3-dependent models.ConclusionsMutant-FGFR3 is an oncogene per se, inducing bladder tumorigenesis. Patients with early stage bladder lesions could thus potentially benefit from FGFR3 targeting. Our results also reinforce the interest in elucidating the role of AR in bladder carcinogenesis, specifically in FGFR3-mutated driven tumors. Finally, our results suggest FGFR3 expression level in epithelium as a determinant for the FGFR3-driven tumors tissue specificity.
Pubertal sex hormones control transcriptional trajectories in the medial preoptic area
Authors: Hashikawa Koichi , Hashikawa Yoshiko , Liu Yuejia , Rossi Mark A. , Basiri Marcus L. , Chen Jane Y. , Ahmad Omar R. , Mukundan Rishi V. , Johnston Nathan L. , McHenry Jenna A. , Palmiter Richard D. , Rubinow David R. , Zweifel Larry S. , Stuber Garret D. 
Published: September 2021

SummaryPubertal maturation aids development of emotion, cognition, and reproduction. We investigated transcriptional dynamics in the medial preoptic area (MPOA), a hypothalamic center for reproductive behaviors, in male and female mice at single-cell resolution (scRNAseq) during puberty. Defined subsets of neurons expressingSlc32a1andEsr1(Vgat+Esr1+) were the most transcriptionally dynamic compared to other cell types throughout puberty. These cell type specific transcriptional progressions towards adulthood were bidirectionally controlled by the levels of circulating testosterone and estradiol. Selective deletion ofEsr1inSlc32a1-expressing cells in the MPOA prior to puberty arrested transcriptional progression and revealed a sexually dimorphic gene-regulatory network governed by Esr1. Deletion ofEsr1in Vgat+cells prevented the development of mating behavior in both sexes. These analyses reveal both sexually common and dimorphic transcriptional progressions during puberty as well as their regulatory mechanisms, which have important implications towards understanding adaptative and maladaptive processes governing adolescent brain development.
Single cell RNA Sequencing Identifies G-protein Coupled Receptor 87 as a Novel Basal Cell Marker of Distal Honeycomb Cysts in Idiopathic Pulmonary Fibrosis
Authors: Heinzelmann Katharina , Hu Qianjiang , Hu Yan , Dobrinskikh Evgenia , Ulke Henrik M. , Ansari Meshal , Leavitt Colton , Mirita Carol , Trudeau Tammy , Saal Maxwell L. , Rice Pamela , Gao Bifeng , Janssen William J. , Yang Ivana V. , Schiller Herbert B. , Vladar Eszter K. , Lehmann Mareike , Königshoff Melanie 
Published: September 2021

AbstractIdiopathic Pulmonary Fibrosis (IPF) is a progressive and fatal lung disease with limited therapeutic options. Epithelial reprogramming and honeycomb cysts are key pathological features of IPF, however, the IPF distal bronchiole cell subtypes and their potential contribution to IPF development and progression still remain poorly characterized. Here, we utilized single-cell RNA sequencing on enriched EpCAM+ cells of the distal IPF and Donor lung. Using the 10x Genomics platform, we generated a dataset of 47,881 cells and found distinct cell clusters, including rare cell types, such as suprabasal cells recently reported in the healthy lung. We identified G-protein coupled receptor (GPR) 87 as a novel surface marker of distal Keratin (KRT)5+ basal cells. GPR87 expression was localized to distal bronchioles and honeycomb cysts in IPF in situ by RNA Scope and immunolabeling. Modulation of GPR87 in primary human bronchial epithelial cells cultures resulted in impaired airway differentiation and ciliogenesis. Thus, GPR87 is a novel marker and potentially druggable target of KRT5+ basal progenitor cells likely contributing to bronchiole remodeling and honeycomb cyst development in IPF.
Are corporate social responsibility reports informative? Evidence from textual analysis of banks in China
Authors: Ho Jerry C. , Chen Ting-Hsuan , Wu Jia-Jin 
Published: September 2021

PurposeThe authors investigate the association of the constructed corporate social responsibility (CSR) measures with the banks’ profitability, social contributions and CSR spending as well as the market reaction to CSR spending.Design/methodology/approachUsing textual analysis of the CSR reports of banks listed on the Chinese market, the authors construct CSR measures in six domains: business, environment, human rights, corporate governance, charity and social capital. Our textual-based CSR measures contain substantial and valuable information beyond what Rankins CSR ratings offer.FindingsThe findings suggest that banks with stronger engagements and interests in the business-related CSR domain experience higher profitability, while those that are more committed to the corporate governance and charity-related domains create larger social contributions. Banks tend to incur higher CSR spending when they are more active in corporate governance. Although the stock market reacts positively to CSR expenditures, the reaction is less favorable for banks with CSR expenditures above the industry norm.Practical implicationsThis study offers insights to policymakers of the regulatory bodies and the banks in China. To enhance the financial safety and soundness of the banking system, the regulatory bodies should encourage banks to strategically allocate corporate resources to achieve higher CSR ratings and engage more business-related CSR activities. To create larger social values, bank management should invest more in philanthropic CSR initiatives such as corporate governance and charity activities. To pursue higher corporate profits, they should engage more in self-centered business-related CSR activities. However, according to the reaction of the market, they should not over-invest in CSR activities.Originality/valueWhile the use of textual analysis to evaluate CSR disclosure has recently emerged in the literature, few studies focus on banks in China. Using the term frequency–inverse data frequency (TF-IDF) method, the authors constructed a score for each of the six CSR domains: business (BUS), environment (ENV), human rights (HR), corporate governance (GOV), charity (CHY) and social capital (SCAP). To the best of our knowledge, no studies have adopted the textual approach to evaluate social reporting quality and CSR activities in the context of the banking industry in China.
Trends and developments of on-site crane layout planning 1983–2020: bibliometric, scientometric and qualitative analyses
Authors: Tariq Salman , Hussein Mohamed , Wang Roy Dong , Zayed Tarek 
Published: September 2021

Purpose
This study aims to thoroughly examine the trends and developments of crane layout planning (CLP) in the construction field and reveal future research directions for modular integrated construction (MiC).

Design/methodology/approach
Through a rigorous systematic mixed-review methodology that integrates bibliometric, scientometric and qualitative analysis, this study explored the crane layout research trend; the scientometric analysis of journal sources and keywords occurrence network; the research contributions and links between influential countries; the classification of research articles based on the type of problems and solution approaches; the qualitative analysis of existing findings and research gaps; and the future research direction for CLP in MiC.

Findings
This study found five categories under the CLP domain, namely, crane selection, crane location, integrated crane selection and location, integrated crane location and allocation of supply points and hybrid problems. The major research approaches used to solve CLP is optimization (43%), visualization (23%), decision support systems (16%), simulation (11%) and qualitative techniques (7%). The possible future research directions include artificial intelligence-based models, multi-crane locations, CLP for MiC re-use, dynamic models representing real-life scenarios and building information modeling-based virtual reality models.

Originality/value
Through a mixed-review methodology, this study provides a comprehensive analysis of problem settings and solution methods of CLP while mitigating the subjectivity of traditional review methods. Also, it presents a repertoire on CLP and illuminates future directions for seasoned researchers in the context of MiC.