bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic changes in gas solubility of xylem sap reiterate the enigma of plant water transport under negative pressure
Authors: Pereira Luciano , Jansen Steven , Miranda Marcela T. , Pacheco Vinícius S. , Kaack Lucian , Pires Gabriel S. , Guan Xinyi , Mayer Juliana L.S. , Machado Eduardo C. , Schenk H. Jochen , Ribeiro Rafael V.
Published: January 2022

Despite a long research history, we do not fully understand why plants are able to transport xylem sap under negative pressure without constant failure. Microbubble formation via direct gas entry is assumed to cause hydraulic failure, while the concentration of gas dissolved in xylem sap is traditionally supposed to be constant, following Henry’s law. Here, the concentration of soluble gas in xylem sap was estimatedin vivousing well-wateredCitrusplants under varying levels of air temperature and photoperiodic exposure, and compared to modelled data. The gas concentration in xylem sap showed non-equilibrium curves, with a minimum over- or undersaturation of 5% compared to gas solubility based on Henry’s law. A similar diurnal pattern was obtained from the gas concentration in the cut-open conduits and discharge tube, and oversolubility was strongly associated with decreasing xylem water potentials during transpiration. Although our model did not explain the daily changes in gas solubility for an anisobaric situation, oversolubility characterises nanoconfined liquids, such as sap inside cell walls. Thus, plants are able to transport sap under negative pressure with relatively high amounts of dissolved gas, providing them with a buffering capacity to prevent hydraulic failure, despite diurnal changes in pressure and temperature.
Genome-wide SNPs of vegetable leafminer, Liriomyza sativae: insights into the recent Australian invasion
Authors: Xu Xuefen , Schmidt Tom L. , Liang Jiaxin , Ridland Peter M. , Chung Jessica , Yang Qiong , Jasper Moshe , Umina Paul A. , Hoffmann Ary A.
Published: January 2022

Liriomyza sativae, the vegetable leafminer, is a serious agricultural pest originally from the Americas which has now colonized all continents except Antarctica. In 2015, L. sativae arrived on the Australian mainland and established on the Cape York Peninsula in the northeast of the country. Here, we assessed genetic variation in L. sativae based on genome-wide single nucleotide polymorphisms (SNPs) generated by double-digest restriction-site associated DNA sequencing (ddRAD-seq) to uncover the potential origin(s) of this pest in Australia and contribute to reconstructing its global invasion history. Our principal component analyses (PCA) results suggested that Australian mainland populations were genetically close to populations from the Torres Strait and had connections to Bali and Papua New Guinea (PNG), whereas populations from Asia and Africa were more distantly related. Hawaii was genetically distinct from populations from Asia, Africa and Australia. Co-ancestry analyses pointed to signals of gene flow from the Torres Strait into the Australian mainland, while Indonesia/PNG were the likely sources of the initial invasion into the Torres Strait. Admixture analyses further revealed that L. sativae from the Torres Strait had genetic diversity originating from multiple sources, which has now spread to the Australian mainland. The L. sativae lineages from Asia/Africa appear closely related and may share co-ancestry. Isolation by distance (IBD) was found at a broad global scale, but not within small regions, suggesting human-mediated factors contribute to the local spread of this pest. Overall, our findings highlight the challenges in quarantine measures aimed at restricting the distribution of this global pest.
Regulation of major bacterial survival strategies by transcript sequestration in a membraneless organelle
Authors: Szoke Tamar , Albocher Nitsan , Goldberger Omer , Barsheshet Meshi , Nussbaum-Shochat Anat , Wiener Reuven , Schuldiner Maya , Amster-Choder Orna
Published: January 2022

Liquid-liquid phase separation (LLPS) of proteins was shown in recent years to regulate spatial organization of cell content without the need for membrane encapsulation in eukaryotes and prokaryotes. Yet evidence for the relevance of LLPS for bacterial cell functionality is largely missing. Here we show that the sugar metabolism-regulating clusters, recently shown by us to assemble in theE. colicell poles by means of the novel protein TmaR, are formed via LLPS. A mutant screen uncovered residues and motifs in TmaR that are important for its condensation. Upon overexpression, TmaR undergoes irreversible liquid-to-solid transition, similar to the transition of disease-causing proteins in human, which impairs bacterial cell morphology and proliferation. Not only does RNA contribute to TmaR phase separation, but by ensuring polar localization and stability of flagella-related transcripts, TmaR enables cell motility and biofilm formation, thus providing a linkage between LLPS and major survival strategies in bacteria.
Sperm exposure to accessory gland secretions alters the transcriptomic response of the endometrium in cattle
Authors: Sánchez José María , Rabaglino María Belén , Bagés-Arnal Sandra , McDonald Michael , Behura Susanta K , Spencer Thomas E , Lonergan Pat , Fernandez-Fuertes Beatriz
Published: January 2022

In a recent study from our group, mating to intact, but not vasectomised, bulls modified the endometrial transcriptome, suggesting an important role of sperm in the modulation of the uterine environment in this species. However, it is not clear whether these changes are driven by intrinsic sperm factors, or by factors of accessory gland (AG) origin that bind to sperm at ejaculation. Thus, the aim of the present study was to determine whether ejaculated sperm, which are suspended in the secretions of the AGs, elicit a different endometrial transcriptomic response than epididymal sperm, which have never been exposed to AG factors. To this end, bovine endometrial explants collected from heifers in oestrus were incubated alone (control), or with epididymal or ejaculated sperm. RNA-sequencing revealed 1912 differentially expressed genes (DEGs) between in endometrial explants exposed to epididymal sperm compared with control explants, whereas 115 DEGs genes detected between endometrial explants exposed to ejaculated sperm in comparison to control explants. In both cases, the top pathways associated with these genes included T cell regulation and NF-KB and IL17 signalling. To confirm whether AG factors were directly responsible for the dampening of the endometrial response elicited by ejaculated sperm, endometrial explants were incubated with epididymal sperm previously exposed, or not, to seminal plasma (SP). Exposure to SP abrogated the downregulation of SQSTM1 by epididymal sperm, and partially inhibited the upregulation of MYL4 and CHRM3 and downregulation of SCRIB. These data indicate that factors of AG origin modulate the interaction between sperm and the endometrium in cattle.
Multiomic analisys reveals that viroid infection induces a temporal reprograming of plant-defence mechanisms at multiple regulatory levels
Authors: Márquez-Molins Joan , Villalba-Bermell Pascual , Corell-Sierra Julia , Pallás Vicente , Gómez Gustavo
Published: January 2022

Viroids are circular RNAs of minimal complexity compelled to subvert plant-regulatory networks to accomplish their infectious process. Studies focused on the response to viroid infection have mostly addressed specific regulatory levels and considered a unique infection time. Thus, much remains to be done to understand the temporal evolution and complex nature of viroid-host interactions. Here we present an integrative analysis of the temporal evolution and intensity of the genome-wide alterations in cucumber plants infected with hop stunt viroid (HSVd) by integrating differential host transcriptome, sRNAnome and methylome. Our results support that HSVd promotes the redesign of the cucumber regulatory-pathways predominantly affecting specific regulatory layers at different infection-phases. The initial response was characterized by a reconfiguration of the host-transcriptome by differential exon usage, followed by a progressive transcriptional down-regulation modulated by epigenetic changes. Regarding endogenous small RNAs, the alterations were limited and mainly occur at the late stage. The most significant host-alterations were predominantly related to the down-regulation of transcripts involved in plant-defence mechanisms, the restriction of pathogen-movement and the systemic spreading of defence signals. Altogether our data evidence the existence of a dynamic and yet poorly known arms race between the host and the viroid. We expect that these data constituting the first comprehensive map of the plant responses to a viroid infection contribute to elucidate the molecular basis of this multifaceted defence and counter-defence layout.
Neural correlate of reduced respiratory chemosensitivity during chronic epilepsy
Authors: Bhandare Amol , Dale Nicholas
Published: January 2022

Central autonomic cardiorespiratory dysfunction underlies sudden unexpected death in epilepsy (SUDEP). Here we used single cell neuronal Ca2+imaging and intrahippocampal kainic acid (KA)-induced chronic epilepsy in mice to investigate progressive changes in key cardiorespiratory brainstem circuits during chronic epilepsy. Following induction of status epilepticus (SE), adaptive ventilatory responses to hypercapnia were reduced in mice with chronic epilepsy for 5 weeks post-SE with partial recovery at week 7. These changes were paralleled by post-SE alterations in the chemosensory responses of neurons in the retrotrapezoid nucleus (RTN). Neurons that displayed adapting responses to hypercapnia were less prevalent and exhibited smaller responses over weeks 3-5, whereas neurons that displayed graded responses to hypercapnia became more prevalent by week 7. Over the same period, chemosensory responses of the presympathetic rostral ventrolateral medullary neurons showed no change. Mice with chronic epilepsy showed enhanced sensitivity to seizures, which can invade the RTN and possibly impair further the chemosensory circuits. Our work suggests that assessment of respiratory chemosensitivity may have potential for identifying people at risk of SUDEP.
Validation that human microbiome phages use alternative genetic coding with TAG stop read as Q
Authors: Peters Samantha L. , Borges Adair L. , Giannone Richard J. , Morowitz Michael J. , Banfield Jillian F. , Hettich Robert L.
Published: January 2022

Metagenomic findings suggesting that bacteriophages (phages) can use genetic codes different from those of their host bacteria reveal a new dimension of phage-host interaction dynamics. Whereas reassignment of stop codons to code for amino acids has been predicted, there has been no proteomic validation of alternative coding in phages. In fact, one code where the stop codon TAG is reassigned to glutamine (code 15) has never been experimentally validated in any biological system. Here, we characterized stop codon reassignment in two crAss-like phages found in the human gut microbiome using LC-MS/MS-based metaproteomics. The proteome data from several phage structural proteins clearly demonstrates reassignment of the TAG stop codon to glutamine, establishing for the first time the expression of genetic code 15.

One-Sentence Summary

Mass spectrometry confirms protein expression of predicted alternate genetic coding in phage genomes from human microbiomes.
Feasibility of Using Wearable EMG Armbands combined with Unsupervised Transfer Learning for Seamless Myoelectric Control
Authors: Sohn M. Hongchul , Lai Sonia Yuxiao , Elwin Matthew L. , Dewald Julius P.A.
Published: January 2022

Myoelectric control uses electromyography (EMG) signals as human-originated input to enable intuitive interfaces with machines. As such, recent rehabilitation robotics employs myoelectric control to autonomously classify user intent or operation mode using machine learning. However, performance in such applications inherently suffers from the non-stationarity of EMG signals across measurement conditions. Current laboratory-based solutions rely on careful, time-consuming control of the recordings or periodic recalibration, impeding real-world deployment. We propose that robust yet seamless myoelectric control can be achieved using a low-end, easy-to-“don” and “doff” wearable EMG sensor combined with unsupervised transfer learning. Here, we test the feasibility of one such application using a consumer-grade sensor (Myo armband, 8 EMG channels @ 200 Hz) for gesture classification across measurement conditions using an existing dataset: 5 users x 10 days x 3 sensor locations. Specifically, we first train a deep neural network using Temporal-Spatial Descriptors (TSD) with labeled source data from any particular user, day, or location. We then apply the Self-Calibrating Asynchronous Domain Adversarial Neural Network (SCADANN), which automatically adjusts the trained TSD to improve classification performance for unlabeled target data from a different user, day, or sensor location. Compared to the original TSD, SCADANN improves accuracy by 12±5.2% (avg±sd), 9.6±5.0%, and 8.6±3.3% across all possible user-to-user, day-to-day, and location-to-location cases, respectively. In one best-case scenario, accuracy improves by 26% (from 67% to 93%), whereas sometimes the gain is modest (e.g., from 76% to 78%). We also show that the performance of transfer learning can be improved by using a “better” model trained with “good” (e.g., incremental) source data. We postulate that the proposed approach is feasible and promising and can be further tailored for seamless myoelectric control of powered prosthetics or exoskeletons.
Ramp-shaped neural tuning supports graded population-level representation of the object-to-scene continuum
Authors: Park Jeongho , Josephs Emilie , Konkle Talia
Published: January 2022

We can easily perceive the spatial scale depicted in a picture, regardless of whether it is a small space (e.g., a close-up view of a chair) or a much larger space (e.g., an entire class room). How does the human visual system encode this continuous dimension? Here, we investigated the underlying neural coding of depicted spatial scale, by examining the voxel tuning and topographic organization of brain responses. We created naturalistic yet carefully-controlled stimuli by constructing virtual indoor environments, and rendered a series of snapshots to smoothly sample between a close-up view of the central object and far-scale view of the full environment (object-to-scene continuum). Human brain responses were measured to each position using functional magnetic resonance imaging. We did not find evidence for a smooth topographic mapping for the object-to-scene continuum on the cortex. Instead, we observed large swaths of cortex with opposing ramp-shaped profiles, with highest responses to one end of the object-to-scene continuum or the other, and a small region showing a weak tuning to intermediate scale views. Importantly, when we considered the multi-voxel patterns of the entire ventral occipito-temporal cortex, we found smooth and linear representation of the object-to-scene continuum. Thus, our results together suggest that depicted spatial scale is coded parametrically in large-scale population codes across the entire ventral occipito-temporal cortex.
Analysis of commonly expressed genes between first trimester fetal heart and placenta cell types in the context of congenital heart disease
Authors: Wilson Rebecca L. , Yuan Victor , Courtney Jennifer , Tipler Alyssa , Cnota James , Jones Helen N.
Published: January 2022

Congenital heart disease (CHD) is often associated with fetal growth abnormalities. During the first trimester of pregnancy, the heart and placenta develop concurrently, and share key developmental pathways. Hence, it is hypothesized that defective morphogenesis of either organ is synergistically linked. However, many studies determined to understand the mechanisms behind CHD overlook the contribution of the placenta. In this study, we aimed to identify commonly expressed genes between first trimester heart and placenta cells using two publicly available single cell sequencing databases. Using a systematic computational approach, we identified 328 commonly expressed genes between heart and placenta endothelial cells and enrichment in pathways including Vasculature Development (GO:0001944, FDR 2.90E-30), and Angiogenesis (GO:0001525, FDR 1.18E-27). We also found, in comparison with fetal heart endothelial cells, 197 commonly expressed genes with placenta extravillous trophoblasts, 128 with cytotrophoblasts and 80 with syncytiotrophoblasts, and included genes such as FLT1, GATA2, ENG and CDH5. Finally, comparison of first trimester cardiomyocytes and placenta cytotrophoblasts revealed 53 commonly expressed genes and enrichment in biological processes integral to cellular function including Cellular Respiration (GO:0045333; FDR 5.05E-08), Ion Transport (GO:0006811; FDR 2.08E-02), and Oxidation-Reduction Process (GO:0055114; FDR 1.58E-07). Overall, our results identify specific genes and cellular pathways common between first trimester fetal heart and placenta cells which if disrupted may concurrently contribute to the developmental perturbations resulting in CHD.
The principal mitochondrial K+ uniport is associated with respiratory complex I
Authors: Zemel Michael , Angelin Alessia , Potluri Prasanth , Wallace Douglas C. , Fieni Francesca
Published: January 2022

This manuscript has been withdrawn by the authors due to disagreement with UCSF over data rights.

This withdrawal decision is not related to the validity of the data presented in this study, and these authors understand that this work cannot be cited as reference for the project until the disagreement is resolved.
Moment-Based Estimation of State-Switching Rates in Cell Populations
Authors: Saint-Antoine Michael , Singh Abhyudai
Published: January 2022

In isogenic cell populations, cells can switch back and forth between different gene expression states. These expression states can be biologically relevant. For example, a certain expression state may cause a tumor cell to be resistant to treatment, while another state may leave it vulnerable to treatment. However, estimating the rates of state-switching can be difficult, because experimentally measuring a cell’s transcriptome often involves destroying the cell, so it can only be measured once. In this paper, we propose a computational method to estimate the rate of switching between expression states, given data from a Luria-Delbrück style fluctuation test that is experimentally simple and feasible. We then benchmark this method using simulated data to test its efficacy, with varying assumptions made about cell cycle timing distribution in the simulations.
Target binding triggers hierarchical phosphorylation of human Argonaute-2 to promote target release
Authors: Bibel Brianna , Elkayam Elad , Silletti Steve , Komives Elizabeth A , Joshua-Tor Leemor
Published: January 2022

Argonaute (Ago) proteins play a central role in post-transcriptional gene regulation through RNA interference (RNAi). Agos bind small RNAs (sRNAs) including small interfering RNAs (siRNAs) and microRNAs (miRNAs) to form the functional core of the RNA Induced Silencing Complex (RISC). The sRNA is used as a guide to target mRNAs containing either partially or fully complementary sequences, ultimately leading to down regulation of the corresponding proteins. It was previously shown that the kinase CK1α phosphorylates a cluster of residues in the eukaryotic insertion (EI) of Ago, leading to the alleviation of miRNA-mediated repression through an undetermined mechanism. We show that binding of miRNA-loaded human Ago2 to target RNA with complementarity to the seed and 3’ supplemental regions of the miRNA primes the EI for hierarchical phosphorylation by CK1α. The added negative charges electrostatically promote target release, freeing Ago to seek out additional targets once it is dephosphorylated. The high conservation of potential phosphosites in the EI suggests that such a regulatory strategy may be a shared mechanism for regulating miRNA-mediated repression.
Release of acidic store calcium is required for effective priming of the NLRP3 inflammasome
Authors: Platt Nick , Shepherd Dawn , Weng Yuzhe , Churchill Grant C. , Galione Antony , Platt Frances M.
Published: January 2022

The lysosome is a dynamic signaling organelle that is critical for cell functioning. It is a regulated calcium store that can contribute to Ca2+-regulated processes via both local calcium release and more globally by influencing ER Ca2+ release. Here, we provide evidence from studies of an authentic mouse model of the lysosomal storage disease Niemann-Pick Type C (NPC) that has reduced lysosomal Ca2+ levels, and genetically modified mice in which the two-pore lysosomal Ca2+ release channel family are deleted that lysosomal Ca2+ signaling is required for normal pro-inflammatory responses. We demonstrate that production of the pro-inflammatory cytokine IL-1β via the NLRP3 inflammasome is significantly reduced in murine Niemann-Pick Type C, the inhibition is selective because secretion of TNFα is not diminished and it is a consequence of inefficient inflammasome priming. Synthesis of precursor ProIL-1β is significantly reduced in macrophages genetically deficient in the lysosomal protein Npc1, which is mutated in most clinical cases of NPC, and in wild type cells in which Npc1 activity is pharmacologically inhibited. Comparable reductions in ProIL-1β generation were measured in vitro and in vivo by macrophages (MΦ) genetically altered to lack expression of the two-pore lysosomal Ca2+ release channels Tpcn1 or Tpcn2. These data demonstrate a requirement for lysosome-dependent Ca2+ signaling in the generation of specific pro-inflammatory responses.
Receptor interacting protein kinase-3 mediates both myopathy and cardiomyopathy in preclinical animal models of Duchenne muscular dystrophy
Authors: Bencze Maximilien , Periou Baptiste , Punzón Isabel , Barthélémy Inès , Taglietti Valentina , Hou Cyrielle , Zaidan Louai , Kefi Kaouthar , Blot Stéphane , Agbulut Onnik , Gervais Marianne , Derumeaux Geneviève , Tiret Laurent , Authier François-Jérôme , Relaix Fréderic
Published: January 2022

Background

Duchenne muscular dystrophy (DMD) is a progressive muscle degenerative disorder, culminating in a complete loss of ambulation, hypertrophic cardiomyopathy and a fatal cardiorespiratory failure.

Necroptosis is the form of necrosis that is dependent upon the receptor-interacting protein kinase (RIPK) 3; it is involved in several inflammatory and neurodegenerative conditions. We previously identified RIPK3 as a key player in the acute myonecrosis affecting the hindlimb muscles of the dystrophic mouse model, mdx. Whether necroptosis also mediates respiratory and heart disorders in DMD is currently unknown.

Methods

Evidence of activation of the necroptotic axis was examined in dystrophic tissues from Golden retriever muscular dystrophy (GRMD) dogs and R-DMDdel52 rats. A functional assessment of the involvement of necroptosis in dystrophic animals was performed on mdx mice that were genetically depleted for RIPK3. Dystrophic mice aged from 12 to 18 months were analyzed by histology and molecular biology to compare the phenotype of muscles from mdxRipk3+/+and mdxRipk3-/-mice. Heart function was also examined by echocardiography in 40-week-old mice.

Results

Quantification ofRIPK3transcripts in sartorius and biceps femoris muscles from GRMD dogs positively correlated to myonecrosis levels (r=0.81; p=0.0076).RIPK3was also found elevated in the diaphragm (p=0<0.05). In the slow progressing heart phenotype of GRMD dogs, the phosphorylated form of RIPK1 at the Serine 161 site was dramatically increased in cardiomyocytes. A similar p-RIPK1 upregulation characterized the cardiomyocytes of R-DMDdel52 rats, associated with a marked overexpressionof Ripk1(p=0.007) andRipk3(p=0.008), indicating primed activation of the necroptotic pathway in the dystrophic heart. MdxRipk3-/-mice displayed decreased compensatory hypertrophy of the heart (p=0.014), and echocardiography showed a 19% increase in the relative wall thickness (p<0.05) and 29% reduction in the left ventricle mass (p=0.0144). Besides, mdxRipk3-/-mice presented no evidence of a regenerative default or sarcopenia in skeletal muscles, moreover around 50% less affected by fibrosis (p<0.05).

Conclusions

Our data provide evidence of the activation of the necroptotic pathway in degenerative tissues from dystrophic animal models, including the diaphragm and the heart. The genetic inhibition of necroptosis in dystrophic mice improves both cardiac function and histological features of muscles, suggesting that prevention of necroptosis is susceptible to providing multiorgan beneficial effects for DMD.
Ligand bias underlies differential signaling of multiple FGFs via FGFR1
Authors: Karl Kelly , Del Piccolo Nuala , Light Taylor , Roy Tanaya , Dudeja Pooja , Ursachi Vlad-Constantin , Fafilek Bohumil , Krejci Pavel , Hristova Kalina
Published: January 2022

The mechanism of differential signaling of multiple FGF ligands through a single FGF receptor is poorly understood. Here, we use biophysical tools to quantify multiple aspects of FGFR1 signaling in response to FGF4, FGF8 and FGF9: potency, efficacy, bias, ligand-induced oligomerization and downregulation, and conformation of the active FGFR1 dimers. We find that the three ligands exhibit distinctly different potencies and efficacies for inducing responses in cells. We further discover qualitative differences in the actions of the three FGFs through FGFR1, as FGF8 preferentially activates some of the probed downstream responses (FRS2 phosphorylation and extracellular matrix loss), while FGF4 and FGF9 preferentially activate different probed responses (FGFR1 phosphorylation and cell growth arrest). Thus, FGF8 is a biased ligand, when compared to FGF4 and FGF9. Förster resonance energy transfer experiments reveal a correlation between biased signaling and the conformation of the FGFR1 transmembrane domain dimer. Our findings expand the mechanistic understanding of FGF signaling during development and bring the poorly understood concept of receptor tyrosine kinase ligand bias into the spotlight.
Acquisition of cross-azole tolerance and aneuploidy inCandida albicansstrains evolved to posaconazole
Authors: Kukurudz Rebekah J. , Chapel Madison , Wonitowy Quinn , Bukari Abdul-Rahman Adamu , Sidney Brooke , Sierhuis Riley , Gerstein Aleeza C.
Published: January 2022

A number ofin vitrostudies have examined the acquisition of drug resistance to the triazole fluconazole, a first-line treatment for many Candida infections. Much less is known about posaconazole, a newer triazole. We conducted the firstin vitroexperimental evolution of replicates from eight diverse strains ofC. albicansin a high level of the fungistatic drug posaconazole. Approximately half of the 132 evolved replicates survived 50 generations of evolution, biased towards some of the strain backgrounds. We found that although increases in drug resistance were rare, increases in drug tolerance (the slow growth of a subpopulation of cells in a level of drug above the resistance level) were common across strains. We also found that adaptation to posaconazole resulted in widespread cross-tolerance to other azole drugs. Widespread aneuploidy variation was also observed in evolved replicates from some strain backgrounds. Trisomy of chromosomes 3, 6, and R was identified in 11 of 12 whole-genome sequenced evolved SC5314 replicates. These findings document rampant evolved cross-tolerance among triazoles and highlight that increases in drug tolerance can evolve independently of drug resistance in a diversity ofC. albicansstrain backgrounds.
Extracellular ATP plays an important role in systemic wound response activation
Authors: Myers Ronald J , Fichman Yosef , Stacey Gary , Mittler Ron
Published: January 2022

Mechanical wounding occurs in plants during biotic (e.g., herbivore or pathogen attack) or abiotic (e.g., wind damage or freezing) stresses and is associated with the activation of multiple signaling pathways. These initiate many wound responses at the wounded tissues, as well as trigger long-distance signaling pathways that activate wound responses in tissues that were not affected by the initial wounding event (termed ‘systemic wound response’). Among the different systemic signals activated by wounding are electric signals, calcium and reactive oxygen species (ROS) waves, and different plant hormones such as jasmonic acid. The release of glutamate from cells at the wounded tissues was recently proposed to trigger several different systemic signal transduction pathways via glutamate-like receptors (GLRs). However, the role of another important compound released from cells during wounding (i.e., extracellular ATP; eATP) in triggering systemic responses is not clear. Here we show that eATP that accumulates in wounded leaves and is sensed by the purinoreceptor kinase P2K is required for the activation of the ROS wave during wounding. Application of eATP to unwounded leaves triggered the ROS wave, and the activation of the ROS wave by wounding or eATP application was suppressed in mutants deficient in P2K (i.e., p2k1-3, p2k2, and p2k1-3p2k2). In addition, the expression of several systemic wound response transcripts was suppressed in mutants deficient in P2K during wounding. Our findings reveal that in addition to sensing glutamate via GLRs, eATP sensed by P2Ks is playing a key role in the triggering of systemic wound responses in plants.

One sentence summary

Extracellular ATP plays an important role in triggering the ROS wave and systemic transcriptomics responses during wounding.
Supervised dimensionality reduction for exploration of single-cell data by Hybrid Subset Selection - Linear Discriminant Analysis
Authors: Amouzgar Meelad , Glass David R. , Baskar Reema , Averbukh Inna , Kimmey Samuel C. , Tsai Albert G. , Hartmann Felix J. , Bendall Sean C.
Published: January 2022

Single-cell technologies generate large, high-dimensional datasets encompassing a diversity of omics. Dimensionality reduction enables visualization of data by representing cells in two-dimensional plots that capture the structure and heterogeneity of the original dataset. Visualizations contribute to human understanding of data and are useful for guiding both quantitative and qualitative analysis of cellular relationships. Existing algorithms are typically unsupervised, utilizing only measured features to generate manifolds, disregarding known biological labels such as cell type or experimental timepoint. Here, we repurpose the classification algorithm, linear discriminant analysis (LDA), for supervised dimensionality reduction of single-cell data. LDA identifies linear combinations of predictors that optimally separate a priori classes, enabling users to tailor visualizations to separate specific aspects of cellular heterogeneity. We implement feature selection by hybrid subset selection (HSS) and demonstrate that this flexible, computationally-efficient approach generates non-stochastic, interpretable axes amenable to diverse biological processes, such as differentiation over time and cell cycle. We benchmark HSS-LDA against several popular dimensionality reduction algorithms and illustrate its utility and versatility for exploration of single-cell mass cytometry, transcriptomics and chromatin accessibility data.
Concurrent fMRI demonstrates propagation of TMS effects across task-related networks
Authors: Deng Lifu , Gamboa Olga Lucia , Dannhauer Moritz , Jonnalagadda Anshu , Hamdan Rena , Crowell Courtney , Worth Tory , Peterchev Angel V. , Sommer Marc A. , Cabeza Roberto , Appelbaum Lawrence G. , Davis Simon W.
Published: January 2022

Transcranial magnetic stimulation (TMS) has become an important technique in both scientific and clinical practices, and yet our understanding of how the brain responds to TMS is still limited. Concurrent neuroimaging during TMS may bridge this gap, and emerging evidence suggests widespread that modulatory effects of TMS may be best captured through changes in functional connectivity between distributed networks, rather than local changes in cortical activity. However, the relationship between TMS stimulation parameters and evoked changes in functional connectivity is unknown. In this study, 24 healthy volunteers received concurrent TMS-fMRI while performing a dot-motion direction discrimination task. An MR-compatible coil was used to apply trains of three pulses at 10 Hz rTMS over the primary visual cortex (V1) at the onset of the dot stimuli with four levels of stimulation intensity (20%, 40%, 80%, and 120% of resting motor threshold, RMT). Behavioral results demonstrated impairment of motion discrimination at 80% RMT. FMRI results yielded three findings. First, functional connectivity between visual and non-visual areas increased as a function of rTMS intensity. Second, connectivitywithinthe visual network was positively associated with motion accuracy, while the connectivitybetweenvisual and non-visual regions was negatively associated with motion accuracy. Lastly, we found that reductions in the similarity between functional and structural connectivity associated with increasing TMS intensity were constrained to the visual network. These findings demonstrate spatially dependent nonlinear effects of TMS intensity on brain functional connectivity that proceed beyond the site of stimulation and influence associated behavior.
Development, validation, and evaluation of prediction models to identify individuals at high risk of lung cancer for screening in the English primary care population using the QResearch® database: research protocol and statistical analysis plan
Authors: Liao Weiqi , Burchardt Judith , Coupland Carol , Gleeson Fergus , Hippisley-Cox Julia ,   DART initiative (WP6)
Published: January 2022

Background and research aim

Lung cancer is a research priority in the UK. Early diagnosis of lung cancer can improve patients’ survival outcomes. The DART-QResearch project is part of a larger academic-industrial collaborative initiative, using big data and artificial intelligence to improve patient outcomes with thoracic diseases. There are two general research aims in the DART-QResearch project: (1) to understand the natural history of lung cancer, (2) to develop, validate, and evaluate risk prediction models to select patients at high risk for lung cancer screening.

Methods

This population-based cohort study uses the QResearch® database (version 45) and includes patients aged between 25 and 84 years old and without a diagnosis of lung cancer at cohort entry (study period: 1 January 2005 to 31 December 2020). The team conducted a literature review (with additional clinical input) to inform the inclusion of variables for data extraction from the QResearch database. The following statistical techniques will be used for different research objectives, including descriptive statistics, multi-level modelling, multiple imputation for missing data, fractional polynomials to explore non-linear relationships between continuous variables and the outcome, and Cox regression for the prediction model. We will update our QCancer (lung, 10-year risk) algorithm, and compare it with the other two mainstream models (LLP and PLCOM2012) for lung cancer screening using the same dataset. We will evaluate the discrimination, calibration, and clinical usefulness of the prediction models, and recommend the best one for lung cancer screening for the English primary care population.

Discussion

The DART-QResearch project focuses on both symptomatic presentation and asymptomatic patients in the lung cancer care pathway. A better understanding of the patterns, trajectories, and phenotypes of symptomatic presentation may help GPs consider lung cancer earlier. Screening asymptomatic patients at high risk is another route to achieve earlier diagnosis of lung cancer. The strengths of this study include using large-scale representative population-based clinical data, robust methodology, and a transparent research process. This project has great potential to contribute to the national cancer strategic plan and yields substantial public and societal benefits through earlier diagnosis of lung cancer.
The layer silicate Cs2SnIVSi6O15
Authors: Ketter Michael , Weil Matthias
Published: January 2022

Single crystals of Cs2SnSi6O15, dicaesium tin(IV) hexasilicate, were serendipitously obtained from a CsCl/NaCl flux at 923 K, starting from mixtures of CaO, SnO and TeO2 in a closed silica ampoule. The crystal structure of Cs2SnSi6O15 is constructed from {Si6O15}6– layers extending parallel to (101), and CsI cations with a coordination number of eleven as well as isolated [SnO6] octahedra situated between the silicate layers. Each of the nine different SiO4 tetrahedra in the silicate layer has a connectedness of Q
3 (three bridging and one terminal O atom), which leads to the formation of five- and eight-membered rings. The same type of silicate layer is found in the crystal structure of the mineral zeravshanite. Comparison with other silicates of the type Cs2
M
IVSi6O15 (M
IV = Ti, Zr, Th, U) revealed a klassengleiche group–subgroup relationship of index 2 between Cs2ZrSi6O15 (Z = 6, space group C2/m) and Cs2SnSi6O15 (Z = 12, space group I2/c).
Synthesis, crystal structure and Hirshfeld surface analysis of 1-ferrocenylundecane-1,11-diol
Authors: McAdam C. John , Simpson Jim
Published: January 2022

The racemic title compound, [Fe(C5H5)(C16H27O2)], comprises an α,ω-diol-substituted undecyl chain with a ferrocenyl substituent at at one terminus. The alkane chain is inclined to the substituted ring of the ferrocene grouping by 84.22 (13)°. The ferrocene rings are almost eclipsed and parallel. The crystal structure features O—H...O and C—H...O hydrogen bonds and C—H...π contacts that stack the molecules along the c-axis direction. A Hirshfeld surface analysis reveals that H...H interactions (83.2%) dominate the surface contacts.
Crystal structure and Hirshfeld surface analysis of 1-[(benzyldimethylsilyl)methyl]-1-ethylpiperidin-1-ium ethanesulfonate
Authors: Kirchhoff Jan-Lukas , Koller Stephan G. , Louven Kathrin , Strohmann Carsten
Published: January 2022

The title molecular salt, C17H30NSi+·C2H5O4S−, belongs to the class of a-aminosilanes and was synthesized by the alkylation of 1-[(benzyldimethylsilyl)methyl]piperidine using diethyl sulfate. This achiral salt crystallizes in the chiral space group P21. One of the Si—C bonds in the cation is unusually long [1.9075 (12) Å], which correlates with the adjacent quaternary N+ atom and was verified by quantum chemical calculations. In the crystal, the components are linked by weak C—H...O hydrogen bonds: a Hirshfeld surface analysis was performed to further investigate these intermolecular interactions and their effects on the crystal packing.
Crystal structure and Hirshfeld surface analysis of (Z)-4-{[4-(3-methyl-3-phenylcyclobutyl)thiazol-2-yl]amino}-4-oxobut-2-enoic acid
Authors: Simsek Okan , Dincer Muharrem , Dege Necmi , Saif Eiad , Yilmaz Ibrahim , Cukurovali Alaaddin
Published: January 2022

The title cyclobutyl compound, C18H18N2O3S, was synthesized by the interaction of 4-(3-methyl-3-phenylcyclobutyl)thiazol-2-amine and maleic anhydride, and crystallizes in the orthorhombic space group P212121 with Z′ = 1. The molecular geometry is partially stabilized by an intramolecular N—H...O hydrogen bond forming an S
1
1(7) ring motif. The molecule is non-planar with a dihedral angle of 88.29 (11)° between the thiazole and benzene rings. In the crystal, the molecules are linked by O—H...N hydrogen bonds, forming supramolecular ribbons with C
1
1(9) chain motifs. To further analyze the intermolecular interactions, a Hirshfeld surface analysis was performed. The results indicate that the most important contributions to the overall surface are from H...H (43%), C...H (18%), O...H (17%) and N...H (6%), interactions.
[Sulfonylbis(bromomethylene)]dibenzene
Authors: Corfield Peter W. R.
Published: January 2022

The title compound, C14H12Br2O2S, crystallizes as the meso isomer of a diastereoisomeric pair. This structure determination was key to determining that the 1,3 elimination of bromine by triphenylphosphine occurs with inversion of the configuration at each of the two chiral carbon atoms. In the crystal, the molecules are linked by weak C—H...O and C—H...Br hydrogen bonds.
A review of 20 years of takaful literature using a systematic method
Authors: Ansari Zahin
Published: January 2022

Purpose

The study aims to summarize the 20 years of literature published in takaful between 2000 and 2019 and propose some key areas as the directions for future research.

Design/methodology/approach

The present study utilizes the systematic method of reviewing the literature. The SCOPUS database has been accessed, and 96 articles have been accounted for the analysis. The articles are grouped in their exclusive themes, such as consumer behavior, financial and nonfinancial performance, takaful models, human resources and governance.

Findings

Takaful research has widely covered marketing, finance, human resource, governance and stresses on its legal issues. Both qualitative and quantitative methodologies have been employed. The research gaps have been classified based on the respective areas. Large share of current body of takaful literature consists of the studies related to the application of behavioural theories to examine the behavioural intention to take up takaful services.

Originality/value

The study enriches the literature of takaful by reviewing articles according to their respective themes, thereby contributing to the significant findings missing from existing literature surveys.
Barriers of growth within an informal sector business: narratives of women subsistence entrepreneurs in South Africa
Authors: Shava Herring , Chinyamurindi Willie
Published: January 2022

Purpose

The study explores growth barriers experienced by a sample of women subsistence entrepreneurs operating within the informal sector in South Africa.

Design/methodology/approach

The paper utilizes a descriptive-exploratory research approach and design relying on semi-structured interviews. A purposive sample of 45 women subsistence entrepreneurs formed the participant pool.

Findings

Three main narratives emerged. First, a sense of personal contentment existed as a potential barrier for women subsistence entrepreneurs. Second, the women subsistence entrepreneurs had no expansion strategy due to their circumstances. This served as a barrier to growth. Finally, challenges emanating from the home-front served as a limit to the growth of the informal sector business.

Research limitations/implications

Based on the findings, strategies are offered to assist the women subsistence entrepreneurs in tackling the identified barriers to the growth of the informal sector business. A limitation of the research concerns issues that accompany qualitative research. Notably, these include sampling issues.

Practical implications

Based on the findings, strategies are offered to assist women subsistence entrepreneurs in tackling the barriers that affect their businesses.

Originality/value

Given the popularity of the informal sector in emerging nations such as South Africa, the study proffers suggestions that assist the advancement of subsistence entrepreneurship, especially within the informal sector. The role of women in all this is heightened.
Giving voice to the voiceless: connecting graduate students with high school students by incubating DRR plans through participatory mapping
Authors: Trejo-Rangel Miguel Angel , Mota Ferreira Adriano , Marchezini Victor , Rodriguez Daniel Andres , Oliveira Melissa da Silva , Messias dos Santos Daniel
Published: January 2022

Purpose

The purpose of this study is to encourage graduate students to facilitate a participatory mapping activity with high school students, to have their voices heard in the disaster risk reduction (DRR) agenda.

Design/methodology/approach

A participatory mapping, youth-led session, was conducted with 22 high school students, where they had to identify flood and landslide-prone areas. Then, they were asked to propose and plan DRR measures in collaboration with local partners in São Luiz do Paraitinga, Brazil.

Findings

The participatory method engaged the graduate students and the high school students in the DRR debate, allowing them to map hazards and vulnerabilities, and to discuss five incubation projects for enhancing DRR in the city.

Originality/value

This research highlights the importance of involving young people in DRR formulation and planning to build local capacities in younger generations. The outputs were shared with the local civil defense and a local non-governmental organization (NGO), who suggested recommendations to improve the five incubation projects.
Social innovation in managing diversity: COVID-19 as a catalyst for change
Authors: Palalar Alkan Deni̇z , Ozbilgin Mustafa , Kamasak Rifat
Published: January 2022

Purpose

Coronavirus disease 2019 (COVID-19) pandemic had an adverse impact on workforce diversity internationally. While in the Global North, many countries have sophisticated laws and organizational mechanisms and discourses to deal with such adverse impacts on workforce diversity, such structures of diversity management are either ceremonial or poorly developed in the Global South. The global pandemic disproportionately impacted Global North and Global South increases the existing gap due to vaccine rollout inequality and divergence in recoveries. The authors explore social innovation as a possible option for responding to the challenges induced by the COVID-19 pandemic.

Design/methodology/approach

The study draws on interviews in 26 distinctive organizations operating in various industries in Turkey. The authors have adopted a qualitative design to explore how social innovation helps to respond to diversity concerns during the COVID-19 pandemic.

Findings

The authors demonstrate that social innovation presents a viable option for a country with a poorly regulated context of diversity management. Social innovation could help overcome the challenge of the absence of supportive legislation, discourses and practices of diversity in poorly regulated contexts.

Originality/value

The field study revealed several distinct forms of social innovation for diversity management, which emerged as a response to the COVID-19 pandemic. The authors demonstrate that in the absence of supportive diversity management structures and frameworks, social innovation in diversity management at the organizational level could provide a viable response to the emergent needs in the context of the COVID-19 pandemic.