bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Theory for the Diffusive Dynamics of Liquid Condensates
Authors: Hubatsch Lars , Jawerth Louise M. , Love Celina , Bauermann Jonathan , Tang T.-Y. Dora , Bo Stefano , Hyman Anthony A. , Weber Christoph A.
Published: March 2021

To unravel the biological functions of membraneless liquid condensates it is crucial to develop a quantitative understanding of the physics underlying their dynamics. Key processes within such condensates are diffusion and material exchange with their environment. Experimentally, diffusive dynamics are typically probed via fluorescent labels. However, to date we lack a physics-based quantitative framework for the dynamics of labeled condensate components. Here, we derive the corresponding theory, building on the physics of phase separation, and quantitatively validate this framework via experiments. We show that using our theory we can precisely determine diffusion coefficients inside liquid condensates via a spatio-temporal analysis of fluorescence recovery after photobleaching (FRAP) experiments. We showcase the accuracy and precision of our approach by considering space- and time-resolved data of protein condensates and two different polyelectrolyte-coacervate systems. Strikingly, our theory can also be used to determine the diffusion coefficient in the dilute phase and the partition coefficient, without relying on fluorescence measurements in the dilute phase. This bypasses recently described quenching artefacts in the dense phase, which can underestimate partition coefficients by orders of magnitude. Our experimentally verified theory opens new avenues for theoretically describing molecule dynamics in condensates, measuring concentrations based on the dynamics of fluorescence intensities and quantifying rates of biochemical reactions in liquid condensates.
The carbon footprint of bioinformatics
Authors: Grealey Jason , Lannelongue Loïc , Saw Woei-Yuh , Marten Jonathan , Meric Guillaume , Ruiz-Carmona Sergio , Inouye Michael
Published: March 2021

Bioinformatic research relies on large-scale computational infrastructures which have a non-zero carbon footprint. So far, no study has quantified the environmental costs of bioinformatic tools and commonly run analyses. In this study, we estimate the bioinformatic carbon footprint (in kilograms of CO2equivalent units, kgCO2e) using the freely available Green Algorithms calculator (www.green-algorithms.org). We assess (i) bioinformatic approaches in genome-wide association studies (GWAS), RNA sequencing, genome assembly, metagenomics, phylogenetics and molecular simulations, as well as (ii) computation strategies, such as parallelisation, CPU (central processing unit) vs GPU (graphics processing unit), cloud vs. local computing infrastructure and geography. In particular, for GWAS, we found that biobank-scale analyses emitted substantial kgCO2e and simple software upgrades could make GWAS greener, e.g. upgrading from BOLT-LMM v1 to v2.3 reduced carbon footprint by 73%. Switching from the average data centre to a more efficient data centres can reduce carbon footprint by ~34%. Memory over-allocation can be a substantial contributor to an algorithm’s carbon footprint. The use of faster processors or greater parallelisation reduces run time but can lead to, sometimes substantially, greater carbon footprint. Finally, we provide guidance on how researchers can reduce power consumption and minimise kgCO2e. Overall, this work elucidates the carbon footprint of common analyses in bioinformatics and provides solutions which empower a move toward greener research.
Snapshot of the Atlantic Forest canopy: surveying arboreal mammals in a biodiversity hotspot
Authors: Kaizer Mariane C. , Alvim Thiago H.G. , Novaes Claudio L. , Mcdevitt Allan D. , Young Robert J.
Published: March 2021

The Atlantic Forest of South America supports some of the greatest terrestrial biodiversity on our planet but is now reduced to only a small extent of its original forest cover. It hosts a large number of endemic mammalian species but our knowledge on arboreal mammal ecology and conservation has been hindered by the challenges of observing arboreal species from ground level. Camera trapping has proven to be an effective tool in terrestrial mammal monitoring, but the technique has rarely been used for arboreal species. Here we generated data on the arboreal mammal community based on canopy camera trapping for the first time in the Atlantic Forest, focusing on Caparaó National Park, Brazil. We placed 24 infrared camera traps in the forest canopy distributed in seven areas within the Park, operating continuously from January 2017 to June 2019. In this time, they accumulated 4,736 camera-days and generated 2,256 sets of pictures and 30 second videos of vertebrates. Canopy camera traps were able to detect arboreal mammals spanning a wide variety of body sizes. The local mammal assemblage comprised of 15 identifiable species, including the critically endangered northern muriqui (Brachyteles hypoxanthus) and the buffy-headed marmoset (Callithrix flaviceps), and other rare, nocturnal and inconspicuous species. For the first time, we confirmed the occurrence of the thin-spined porcupine (Chaetomys subspinosus) in the Park. Species richness varied across sampling areas and forest types. Our findings demonstrate the potential of canopy camera trapping for future surveying efforts to better inform conservation strategies for mammals.
State anxiety alters the neural oscillatory correlates of predictions and prediction errors during reward learning
Authors: Hein Thomas P , Ruiz Maria Herrojo
Published: March 2021

Anxiety influences how the brain estimates and responds to uncertainty. These behavioural effects have been described within predictive coding and Bayesian inference frameworks, yet the associated neural correlates remain unclear. Recent work suggests that predictions in generative models of perception are represented in alpha (8–12 Hz) and beta oscillations (13–30 Hz). Updates to predictions are driven by prediction errors weighted by precision (inverse variance; pwPE), and are encoded in gamma oscillations (>30 Hz) and associated with suppression of beta activity. We tested whether state anxiety alters the neural oscillatory activity associated with predictions and pwPE during learning. Healthy human participants performed a probabilistic reward-learning task in a volatile environment. In our previous work, we described learning behaviour in this task using a hierarchical Bayesian model, revealing more precise (biased) beliefs about the reward tendency in state anxiety, consistent with reduced learning in this group. The model provided trajectories of predictions and pwPEs for the current study, allowing us to assess their parametric effects on the time-frequency representations of EEG data. Using convolution modelling for oscillatory responses, we found that, relative to a control group, state anxiety increased beta activity in frontal and sensorimotor regions during processing of pwPE, and in fronto-parietal regions during encoding of predictions. No effects of state anxiety on gamma modulation were found. Our findings expand prior evidence on the oscillatory representations of predictions and pwPEs into the reward-learning domain. The results suggest that state anxiety modulates beta-band oscillatory correlates of pwPE and predictions in generative models, providing insights into the neural processes associated with biased belief updating and poorer reward learning.
Variability of EEG electrode positions and their underlying brain regions: visualising gel artifacts from a simultaneous EEG-fMRI dataset
Authors: Scrivener C. L. , Reader A. T.
Published: March 2021

We investigated the between-subject variability of EEG electrode placement from a simultaneously recorded EEG-fMRI dataset. Neuro-navigation software was used to localise electrode positions inxyzand MNI space, made possible by the gel artifacts present in the structural MRI images. To assess variation in the brain regions directly underneath each electrode, we used both raw MNI coordinates and labels from the Harvard-Oxford Cortical atlas. In a sample of 20 participants, the mean standard deviation of electrode placement was 3.94 mm inx, 5.55 mm iny, and 7.17 mm inz, with the largest variation in parietal and occipital electrodes. In addition, the brain regions covered by electrode pairs was not always consistent; for example, the mean location of electrode P07 was mapped to BA18, whereas P08 was closer to BA19. Further, electrode C1 was mapped to the left primary motor cortex, whereas C2 was closer to right pre-motor cortex. Overall, the results emphasise the variation in electrode positioning that can be found even in a fixed cap, potentially caused by between-subject differences in brain morphology. We present a relatively simple method for approximating the location of electrodes in a simultaneous EEG-fMRI data set with accompanying analysis code, and suggest that researchers check the regions underlying their EEG ROIs to improve the generalisability and reliability of their neuroimaging results.
Multimodal image fusion via deep generative models
Authors: Dimitri Giovanna Maria , Spasov Simeon , Duggento Andrea , Passamonti Luca , Lio’ Pietro , Toschi Nicola
Published: March 2021

Recently, it has become progressively more evident that classic diagnostic labels are unable to accurately and reliably describe the complexity and variability of several clinical phenotypes. This is particularly true for a broad range of neuropsychiatric illnesses such as depression and anxiety disorders or behavioural phenotypes such as aggression and antisocial personality. Patient heterogeneity can be better described and conceptualized by grouping individuals into novel categories, which are based on empirically-derived sections of intersectingcontinuathat span both across and beyond traditional categorical borders. In this context, neuroimaging data carry a wealth of spatiotemporally resolved information about each patient’s brain. However, they are usually heavily collapseda priorithrough procedures which are not learned as part of model training, and consequently not optimized for the downstream prediction task. This is due to the fact that every individual participant usually comes with multiple whole-brain 3D imaging modalities often accompanied by a deep genotypic and phenotypic characterization, hence posing formidable computational challenges.

In this paper we design and validate a deep learning architecture based on generative models rooted in a modular approach and separable convolutional blocks (which result in a 20-fold decrease in parameter utilization) in order to a) fuse multiple 3D neuroimaging modalities on a voxel-wise level, b) efficiently convert them into informative latent embeddings through heavy dimensionality reduction, c) maintain excellent generalizability and minimal information loss. As proof of concept, we test our architecture on the well characterized Human Connectome Project database (n=974 healthy subjects), demonstrating that our latent embeddings can be clustered into easily separable subject strata which, in turn, map to extremely different phenotypical information (including organic, neuropsychological, personality variables) which was not included in the embedding creation process.

The ability to extract meaningful and separable phenotypic information from brain images alone can aid in creating multi-dimensional biomarkers able to chart spatio-temporal trajectories which may correspond to different pathophysiological mechanisms unidentifiable to traditional data analysis approaches. In turn, this may be of aid in predicting disease evolution as well as drug response, hence supporting mechanistic disease understanding and also empowering clinical trials.
Vinculin controls endothelial cell junction dynamics during vascular lumen formation
Authors: Kotini Maria P. , van der Stoel Miesje M. , Han Mitchell K. , Kirchmaier Bettina , de Rooij Johan , Affolter Markus , Huveneers Stephan , Belting Heinz-Georg
Published: March 2021

Blood vessel morphogenesis is driven by coordinated endothelial cell behaviors, which depend on dynamic cell-cell interactions. Remodeling of endothelial cell-cell junctions promote morphogenetic cellular events while preserving vascular integrity. Here, we have analyzed the dynamics of endothelial cell-cell junctions during lumen formation in angiogenic sprouts. By live-imaging of the formation of intersegmental blood vessels in zebrafish, we demonstrate that lumen expansion is accompanied by the formation of transient finger-shaped junctions. Formation and maintenance of these junctional fingers are positively regulated by blood pressure whereas inhibition of blood flow prevents their formation. Using fluorescent reporters, we show that the tension-sensor Vinculin localizes to junctional fingers. Furthermore, loss of vinculin function, invinculin aand -bdouble knockouts, prevents junctional finger formation in angiogenic sprouts, whereas endothelial expression of avinculintransgene is sufficient to restore junctional fingers. Taken together, our findings suggest a mechanism in which lumen expansion during angiogenesis leads to an increase in junctional tension, which triggers recruitment of vinculin and formation of junctional fingers. We propose that endothelial cells may employ force-dependent junctional remodeling to react to changes in external forces to protect cell-cell contacts and to maintain vascular integrity during sprouting angiogenesis.
Latent representation of the human pan-celltype epigenome through a deep recurrent neural network
Authors: Dsouza Kevin B. , Li Adam Y. , Bhargava Vijay K. , Libbrecht Maxwell W.
Published: March 2021

The availability of thousands of assays of epigenetic activity necessitates compressed representations of these data sets that summarize the epigenetic landscape of the genome. Until recently, most such representations were celltype specific, applying to a single tissue or cell state. Recently, neural networks have made it possible to summarize data across tissues to produce a pan-celltype representation. In this work, we propose Epi-LSTM, a deep long short-term memory (LSTM) recurrent neural network autoencoder to capture the long-term dependencies in the epigenomic data. The latent representations from Epi-LSTM capture a variety of genomic phenomena, including gene-expression, promoter-enhancer interactions, replication timing, frequently interacting regions and evolutionary conservation. These representations outperform existing methods in a majority of cell-types, while yielding smoother representations along the genomic axis due to their sequential nature.
Rapid Identification of Methylase Specificity (RIMS-seq) jointly identifies methylated motifs and generates shotgun sequencing of bacterial genomes
Authors: Baum Chloé , Yu-Cheng-Lin  , Fomenkov Alexey , Anton Brian P. , Chen Lixin , Evans Thomas C. , Roberts Richard J , Tolonen Andrew C , Ettwiller Laurence
Published: March 2021

DNA methylation is widespread amongst eukaryotes and prokaryotes to modulate gene expression and confer viral resistance. 5-methylcytosine (m5C) methylation has been described in genomes of a large fraction of bacterial species as part of restriction-modification systems, each composed of a methyltransferase and cognate restriction enzyme. Methylases are site-specific and target sequences vary across organisms. High-throughput methods, such as bisulfite-sequencing can identify m5C at base resolution but require specialized library preparations and Single Molecule, Real-Time (SMRT) Sequencing usually misses m5C. Here, we present a new method called RIMS-seq (Rapid Identification of Methylase Specificity) to simultaneously sequence bacterial genomes and determine m5C methylase specificities using a simple experimental protocol that closely resembles the DNA-seq protocol for Illumina. Importantly, the resulting sequencing quality is identical to DNA-seq, enabling RIMS-seq to substitute standard sequencing of bacterial genomes. Applied to bacteria and synthetic mixed communities, RIMS-seq reveals new methylase specificities, supporting routine study of m5C methylation while sequencing new genomes.
Identification of putative causal loci in whole-genome sequencing data via knockoff statistics
Authors: He Zihuai , Liu Linxi , Wang Chen , Guen Yann Le , Lee Justin , Gogarten Stephanie , Lu Fred , Montgomery Stephen , Tang Hua , Silverman Edwin K. , Cho Michael H. , Greicius Michael , Ionita-Laza Iuliana
Published: March 2021

The analysis of whole-genome sequencing studies is challenging due to the large number of rare variants in noncoding regions and the lack of natural units for testing. We propose a statistical method to detect and localize rare and common risk variants in whole-genome sequencing studies based on a recently developed knockoff framework. It can (1) prioritize causal variants over associations due to linkage disequilibrium thereby improving interpretability; (2) help distinguish the signal due to rare variants from shadow effects of significant common variants nearby; (3) integrate multiple knockoffs for improved power, stability and reproducibility; and (4) flexibly incorporate state-of-the-art and future association tests to achieve the benefits proposed here. In applications to whole-genome sequencing data from the Alzheimer’s Disease Sequencing Project (ADSP) and COPDGene samples from NHLBI Trans-Omics for Precision Medicine (TOPMed) Program we show that our method compared with conventional association tests can lead to substantially more discoveries.
Exposure to sevoflurane results in changes of transcription factor occupancy in sperm and inheritance of autism
Authors: Wang Hsiao-Lin V. , Forestier Samantha , Corces Victor G.
Published: March 2021

One in 54 children in the U.S. is diagnosed with Autism Spectrum Disorder (ASD). De novo germline and somatic mutations cannot account for all cases of ASD, suggesting that epigenetic alterations triggered by environmental exposures may be responsible for a subset of ASD cases. Human and animal studies have shown that exposure of the developing brain to general anesthetic (GA) agents can trigger neurodegeneration and neurobehavioral abnormalities but the effects of general anesthetics on the germ line have not been explored in detail. We exposed pregnant mice to sevoflurane during the time of embryonic development when the germ cells undergo epigenetic reprogramming and found that more than 38% of the directly exposed F1 animals exhibit impairments in anxiety and social interactions. Strikingly, 44-47% of the F2 and F3 animals, which were not directly exposed to sevoflurane, show the same behavioral problems. We performed ATAC-seq and identified more than 1,200 differentially accessible sites in the sperm of F1 animals, 69 of which are also present in the sperm of F2 animals. These sites are located in regulatory regions of genes strongly associated with ASD, includingArid1b, Ntrk2, andStmn2. These findings suggest that epimutations caused by exposing germ cells to sevoflurane can lead to ASD in the offspring, and this effect can be transmitted through the male germline inter and trans-generationally.

Summary sentence

Pregnant mouse F0 females exposed to sevoflurane give rise to F1 males with sociability and anxiety defects. These behaviors are transmitted to F2 and F3 males. Their sperm show changes in transcription factor occupancy in genes implicated in autism.
Phage Display Broadly Identifies Inhibitor-reactive Regions in von Willebrand Factor
Authors: Yee Andrew , Dai Manhong , Croteau Stacy E. , Shavit Jordan A. , Pipe Steven W. , Siemieniak David , Meng Fan , Ginsburg David
Published: March 2021

Background

Correction of von Willebrand factor (VWF) deficiency with replacement products containing VWF can lead to the development of anti-VWF alloantibodies (i.e., VWF inhibitors) in patients with severe von Willebrand disease (VWD).

Objective

Locate inhibitor-reactive regions within VWF using phage display.

Methods

We screened a phage library displaying random, overlapping fragments covering the full length VWF protein sequence for binding to a commercial anti-VWF antibody or to immunoglobulins from three type 3 VWD patients who developed VWF inhibitors in response to treatment with plasma-derived VWF. Immunoreactive phage clones were identified and quantified by next generation DNA sequencing (NGS).

Results

NGS markedly increased the number of phage analyzed for locating immunoreactive regions within VWF following a single round of selection and identified regions not recognized in previous reports using standard phage display methods. Extending this approach to characterize VWF inhibitors from three type 3 VWD patients (including two siblings homozygous for the sameVWFgene deletion) revealed patterns of immunoreactivity distinct from the commercial antibody and between unrelated patients, though with notable areas of overlap. Alloantibody reactivity against the VWF propeptide is consistent with incomplete removal of the propeptide from plasma-derived VWF replacement products.

Conclusion

These results demonstrate the utility of phage display and NGS to characterize diverse anti-VWF antibody reactivities.
A novel nitrogen concentrating mechanism in the coral-algae symbiosome
Authors: Thies Angus B. , Quijada-Rodriquez Alex R. , Zhouyao Haonan , Weihrauch Dirk , Tresguerres Martin
Published: March 2021

Coral algal symbionts are hosted inside the symbiosome of gastrodermal cells, an intracellular compartment that isolates algae from the external environment and allows host cells to control the delivery of metabolites to their symbionts. However, the underlying molecular mechanisms are largely unknown. Here, we report the diel trafficking of NH3-transporting Rhesus (Rh) channels between the cytoplasm and the symbiosome membrane in the coralAcropora yongei, which matches established patterns of nitrogen delivery to endosymbionts. Heterologous expression inXenopusoocytes established thatA. yongeiRh (ayRhp1) is a channel that facilitates NH3diffusion across membranes following its partial pressure gradient. Immunostaining revealed ayRhp1 is widely distributed throughout coral tissues and most abundantly present in oral ectodermal cells, desmocytes, and gastrodermal cells. In the latter, ayRhp1 was observed in the symbiosome membrane of alga-containing cells. Together with V-type H+-ATPases that make the symbiosome highly acidic (pH~4), ayRhp1 constitutes an NH4+-trapping mechanism analogous to that in mammalian renal tubule. Remarkably, ayRhp1 presence in the symbiosome membrane was higher during the day than the night. This indicates a regulatory mechanism that facilitates NH4+delivery to alga during the day, likely to sustain high turnover rates of photosynthetic proteins, while restricting NH4+delivery at night to maintain the endosymbiotic algae in a nitrogen-limited stage that stagnates their growth. The dynamic trafficking of proteins to and away from the symbiosome membrane is a previously unknown mechanism that contributes to metabolic regulation between symbiotic partners.

Significance Statement

The endosymbiotic relationship between corals and algae relies on the coordinated exchange of metabolites. Disruption of these metabolic exchanges can result in interruption of the symbiosis; however, the underlying molecular mechanisms are poorly understood. Here we report thatAcropora yongeicoral host cells express ammonia-transporting channel proteins (ayRhp1), which traffic to and away from the symbiosome membrane surrounding the endosymbiotic algae. In conjunction with the acidic symbiosome microenvironment, this mechanism allows host cells to regulate nitrogen delivery to endosymbionts sustaining essential functions while restricting growth. This work provides novel mechanistic information about metabolic regulation of animal-algae symbioses, and advances our understanding of physiological mechanisms that might determine coral local adaptation, resilience, and vulnerability to environmental stress including climate change.
Distributed brain co-processor for tracking electrophysiology and behavior during electrical brain stimulation
Authors: Sladky Vladimir , Nejedly Petr , Mivalt Filip , Brinkmann Benjamin H. , Kim Inyong , St. Louis Erik K. , Gregg Nicholas M. , Lundstrom Brian N. , Crowe Chelsea M. , Pal Attia Tal , Crepeau Daniel , Balzekas Irena , Marks Victoria , Wheeler Lydia P. , Cimbalnik Jan , Cook Mark , Janca Radek , Sturges Beverly K. , Leyde Kent , Miller Kai J. , Van Gompel Jamie J. , Denison Timothy , Worrell Gregory A. , Kremen Vaclav
Published: March 2021

Early implantable epilepsy therapy devices provided open-loop electrical stimulation without brain sensing, computing, or an interface for synchronized behavioral inputs from patients. Recent epilepsy stimulation devices provide brain sensing but have not yet developed analytics for accurately tracking and quantifying behavior and seizures. Here we describe a distributed brain co-processor providing an intuitive bi-directional interface between patient, implanted neural stimulation and sensing device, and local and distributed computing resources. Automated analysis of continuous streaming electrophysiology is synchronized with patient reports using a hand-held device and integrated with distributed cloud computing resources for quantifying seizures, interictal epileptiform spikes, and patient symptoms during therapeutic electrical brain stimulation. The classification algorithms for interictal epileptiform spikes and seizures were developed and parameterized using long-term ambulatory data from 9 humans and 8 canines with epilepsy, and then implemented prospectively in out-of-sample testing in 2 pet canines and 4 humans with drug resistant epilepsy living in their natural environments.
Regulation of oogenesis in the queen honey bee (Apis mellifera)
Authors: Aamidor Sarah E , Cardoso-Júnior Carlos AM , Harianto Januar , Nowell Cameron J , Cole Louise , Oldroyd Benjamin P , Ronai Isobel
Published: March 2021

In the honey bee (Apis mellifera), queen and worker castes originate from identical genetic templates but develop into different phenotypes. Queens lay up to 2,000 eggs daily whereas workers are sterile in the queen’s presence. Periodically queens stop laying; during swarming, when resources are scarce in winter and when they are confined to a cage by beekeepers. We used confocal microscopy and gene expression assays to investigate the control of oogenesis in honey bee queen ovaries. We show that queens use different combination of ‘checkpoints’ to regulate oogenesis compared to honey bee workers and other insect species. However, both queen and worker castes use the same programmed cell death pathways to terminate oocyte development at their caste-specific checkpoints. Our results also suggest that the termination of oogenesis in queens is driven by nutritional stress. Thus, queens may regulate oogenesis via the same regulatory pathways that were utilised by ancestral solitary species but have adjusted physiological checkpoints to suit their highly-derived life history.

Summary statement

Honey bee queens regulate oogenesis using a different combination of ‘checkpoints’ to workers, but both castes use the same molecular pathways.
Stromal inflammation is a targetable driver of hematopoietic aging
Authors: Verovskaya Evgenia V. , Mitchell Carl A. , Calero-Nieto Fernando J. , Hérault Aurélie , Dellorusso Paul V. , Wang Xiaonan , Zhang Si Yi , Svendsen Arthur Flohr , Pietras Eric M. , Bakker Sietske T. , Ho Theodore T. , Göttgens Berthold , Passegué Emmanuelle
Published: March 2021

Hematopoietic aging is marked by a loss of regenerative capacity and skewed differentiation from hematopoietic stem cells (HSC) leading to dysfunctional blood production. Signals from the bone marrow (BM) niche dynamically tailor hematopoiesis, but the effect of aging on the niche microenvironment and the contribution of the aging niche to blood aging still remains unclear. Here, we characterize the inflammatory milieu in the aged marrow cavity that drives both stromal and hematopoietic remodeling. We find decreased numbers and functionality of osteogenic mesenchymal stromal cells (MSC) at the endosteum and expansion of pro-inflammatory perisinusoidal MSCs with deterioration of sinusoidal endothelium in the central marrow, which together create a degraded and inflamed old niche. Molecular mapping at single cell resolution confirms disruption of cell identities and enrichment of inflammatory response genes in niche populations. Niche inflammation, in turn, drives chronic activation of emergency myelopoiesis pathways in old HSCs and multipotent progenitors (MPP), which promotes myeloid differentiation at the expense of lymphoid and erythroid commitment and hinders hematopoietic regeneration. Remarkably, niche deterioration, HSC dysfunction and defective hematopoietic regeneration, can be improved by blocking inflammatory IL-1 signaling. Our results demonstrate that targeting niche inflammation is a tractable strategy to restore blood production during aging.
RBPMS2 is a conserved regulator of alternative splicing that promotes myofibrillar organization and optimal calcium handling in cardiomyocytes
Authors: Akerberg Alexander A. , Trembley Michael , Butty Vincent , Schwertner Asya , Zhao Long , Beerens Manu , Liu Xujie , Mahamdeh Mohammed , Yuan Shiaulou , Boyer Laurie , MacRae Calum , Nguyen Christopher , Pu William T. , Burns Caroline E. , Burns C. Geoffrey
Published: March 2021

Rationale

The identification of novel cardiomyocyte-intrinsic factors that support heart function will expand the number of candidate genes and therapeutic options for heart failure, a leading cause of death worldwide.

Objective

To identify and characterize conserved regulators of cardiomyocyte function.

Methods and Results

We report that the RNA-binding protein RBPMS2 is required for myofibril organization and the regulation of intracellular calcium dynamics in both zebrafish embryos and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). A differential expression screen in zebrafish uncovered enrichment ofrbpms2paralogs,rbpms2aandrbpms2b,in the myocardium. Double knock-out (rbpms2-null) embryos suffer from compromised ventricular filling during the relaxation phase of the cardiac cycle, which significantly reduces cardiac output. Whole transcriptome sequencing and validation studies revealed differential alternative splicing of several genes linked to cardiomyopathies in humans, includingmyosin binding protein C3(mybpc3) andphospholamban(pln), consistent with a role in causing the observed ventricular deficiencies. Further,RBPMS2-null hiPSC-CMs exhibit myofibril and calcium handling defects that are highly analogous to those observed in therbpms2-null zebrafish ventricle.

Conclusions

Taken together, our data identifyRBPMS2as a conserved and essential regulator of alternative splicing that is required for myofibrillar organization and optimal calcium handling from zebrafish to humans.
Functional basis of electron transport within photosynthetic complex I
Authors: Richardson Katherine H. , Wright John J. , Šimėnas Mantas , Thiemann Jacqueline , Esteves Ana M. , McGuire Gemma , Myers William K. , Morton John J.L. , Hippler Michael , Nowaczyk Marc M. , Hanke Guy T. , Roessler Maxie M.
Published: March 2021

Photosynthesis and respiration rely upon a proton gradient to produce ATP. In photosynthesis, the Respiratory Complex I homologue, Photosynthetic Complex I (PS-CI) is proposed to couple ferredoxin oxidation and plastoquinone reduction to proton pumping across thylakoid membranes, and is fundamental to bioenergetics in photosynthetic bacteria and some higher plant cell types. However, little is known about the PS-CI molecular mechanism and attempts to understand its function have previously been frustrated by its large size and high lability. Here, we overcome these challenges by pushing the limits in sample size and spectroscopic sensitivity, to determine arguably the most important property of any electron transport enzyme – the reduction potentials of its cofactors, in this case the iron-sulphur clusters of PS-CI, and unambiguously assign them to the structure using double electron-electron resonance (DEER). We have thus determined the bioenergetics of the electron transfer relay and provide insight into the mechanism of PS-CI, laying the foundations for understanding of how this important bioenergetic complex functions.
Selective and reversible disruption of mitochondrial inner membrane protein complexes by lipophilic cations
Authors: Kafkova Anezka , Tilokani Lisa , Trčka Filip , Šrámková Veronika , Vancová Marie , Bílý Tomáš , Nebesářová Jana , Prudent Julien , Trnka Jan
Published: March 2021

Triphenylphosphonium (TPP) derivatives are commonly used to target chemical into mitochondria. We show that alkyl-TPP cause reversible, dose- and hydrophobicity-dependent alterations of mitochondrial morphology and function and a selective decrease of mitochondrial inner membrane proteins including subunits of the respiratory chain complexes, as well as components of the mitochondrial calcium uniporter complex. The treatment with alkyl-TPP resulted in the cleavage of the pro-fusion and cristae organisation regulator Optic atrophy-1. The structural and functional effects of alkyl-TPP were found to be reversible and not merely due to loss of membrane potential. A similar effect was observed with the mitochondria-targeted antioxidant MitoQ.
ER exit sites inDrosophiladisplay abundant ER-Golgi vesicles and pearled tubes but no megacarriers
Authors: Yang Ke , Liu Min , Feng Zhi , Rojas Marta , Zhou Lingjian , Ke Hongmei , Pastor-Pareja José Carlos
Published: March 2021

Secretory cargos are collected at ER exit sites (ERES) before transport to the Golgi apparatus. Decades of research have provided many details of the molecular events underlying ER-Golgi exchanges. Essential questions, however, remain about the organization of the ER-Golgi interface in cells and the type of membrane structures mediating traffic from ERES. To investigate these, we used transgenic tagging inDrosophilaflies, 3D-SIM and FIB-SEM to characterize ERES-Golgi units in collagen-producing fat body, imaginal discs and imaginal discs overexpressing ERES determinant Tango1. We found in front of ERES a pre-cis-Golgi region involved in both anterograde and retrograde transport. This pre-cis-Golgi is continuous with the rest of the Golgi, not a separate intermediate compartment or collection of large carriers, for which we found no evidence. We found, however, many vesicles, as well as pearled tubules connecting ERES and Golgi.
Genomic analyses provide insights into peach local adaptation and responses to climate change
Authors: Li Yong , Cao Ke , Li Nan , Zhu Gengrui , Fang Weichao , Chen Changwen , Wang Xinwei , Guo Jian , Wang Qi , Ding Tiyu , Wang Jiao , Guan Liping , Wang Junxiu , Liu Kuozhan , Guo Wenwu , Arús Pere , Huang Sanwen , Fei Zhangjun , Wang Lirong
Published: March 2021

The environment has constantly shaped plant genomes, but the genetic bases underlying how plants adapt to environmental influences remain largely unknown. We constructed a high-density genomic variation map of 263 geographically representative peach landraces and wild relatives. A combination of whole-genome selection scans and genome-wide environmental association studies (GWEAS) was performed to reveal the genomic bases of peach adaptation to diverse climates. A total of 2092 selective sweeps that underlie local adaptation to both mild and extreme climates were identified, including 339 sweeps conferring genomic pattern of adaptation to high altitudes. Using genome-wide environmental association studies (GWEAS), a total of 2755 genomic loci strongly associated with 51 specific environmental variables were detected. The molecular mechanism underlying adaptive evolution of high drought, strong UVB, cold hardiness, sugar content, flesh color, and bloom date were revealed. Finally, based on 30 yr of observation, a candidate gene associated with bloom date advance, representing peach responses to global warming, was identified. Collectively, our study provides insights into molecular bases of how environments have shaped peach genomes by natural selection and adds candidate genes for future studies on evolutionary genetics, adaptation to climate changes, and breeding.
The crystal structures, Hirshfeld surface analyses and energy frameworks of 8-{1-[3-(cyclopent-1-en-1-yl)benzyl]piperidin-4-yl}-2-methoxyquinoline and 8-{4-[3-(cyclopent-1-en-1-yl)benzyl]piperazin-1-yl}-2-methoxyquinoline
Authors: Ullah Nisar , Stoeckli-Evans Helen
Published: March 2021

The title compounds, 8-{1-[3-(cyclopent-1-en-1-yl)benzyl]piperidin-4-yl}-2-methoxyquinoline, C27H30N2O (I), and 8-{4-[3-(cyclopent-1-en-1-yl)benzyl]piperazin-1-yl}-2-methoxyquinoline, C26H29N3O (II), differ only in the nature of the central six-membered ring: piperidine in I and piperazine in II. They are isoelectronic (CH cf. N) and isotypic; they both crystallize in the triclinic space group P\overline{1} with very similar unit-cell parameters. Both molecules have a curved shape and very similar conformations. In the biaryl group, the phenyl ring is inclined to the cyclopentene mean plane (r.m.s. deviations = 0.089 Å for I and 0.082 Å for II) by 15.83 (9) and 13.82 (6)° in I and II, respectively, and by 67.68 (6) and 69.47 (10)°, respectively, to the mean plane of the quinoline moiety (r.m.s. deviations = 0.034 Å for I and 0.038 Å for II). The piperazine ring in I and the piperidine ring in II have chair conformations. In the crystals of both compounds, molecules are linked by C—H...π interactions, forming chains in I and ribbons in II, both propagating along the b-axis direction. The principal contributions to the overall Hirshfeld surfaces involve H...H contacts at 67.5 and 65.9% for I and II, respectively. The major contribution to the intermolecular interactions in the crystals is from dispersion forces (E
dis), reflecting the absence of classical hydrogen bonds.
The evolution of meanings: an empirical analysis of the social media industry
Authors: Sanasi Silvia , Trabucchi Daniel , Pellizzoni Elena , Buganza Tommaso
Published: March 2021

Purpose

Innovation dynamics have been the object of study of several researchers, focusing in particular on technological innovation and the emergence of a dominant design. However, these models have been challenged by how the pervasiveness of digital technologies is speeding up the pace at which innovation evolves. On the other hand, a growing body of literature in innovation management has started underlining the relevance of new product and service meanings as a source of innovation.

Design/methodology/approach

This research aims to study the different innovation dynamics within an industry, investigating not only how companies react to fast-changing functional advancements but rather how their behavior changes as shifts in meaning occur. To properly assess the phenomenon, this longitudinal study analyzes the social media industry, strongly subjected to continuous functional advancements, through a deep dive in the 160 innovations introduced between 2003 and 2017 by the eight leading players in the industry.

Findings

Our results illustrate the co-existence of different approaches to innovation within an industry and hint that consequent and fast cycles of innovation in both functionalities and meanings discourage the emergence of a dominant design.

Practical implications

Our results help managers and innovators acknowledge the possibility to leverage not just on the technological dimension of innovation but also the reason why people use a given product or service, innovating its meaning. Furthermore, our results recognize the co-existence of different innovation streams upon which innovators can act.

Originality/value

This research contributes to the extant literature in innovation management, extending the classical models of innovation dynamics by including the evolution of innovations of meaning in relation to technological innovation.
Cuba’s response to COVID-19: lessons for the future
Authors: Wylie Lana L.
Published: March 2021

Purpose

The purpose of this paper is to examine the relevance of Cuba’s medical system, its health tourism and related diplomacy in the context of the recent COVID-19 pandemic for the global response to disease outbreaks. In addition to Cuba being a destination for leisure tourists in the Caribbean, the renowned Cuban medical system attracts thousands of health tourists seeking low-cost but high-quality treatment. This paper demonstrates how Cuba’s unique response to the pandemic, which included sending thousands of medical staff abroad, can inform structural and global issues and contribute to a more sustainable future.

Design/methodology/approach

The research in this study is primarily drawn from published academic and media sources that address Cuba’s medical system, its health tourism and the government’s response to the recent pandemic. The author, a political scientist and an author of many publications on Cuba, and the PI of a study focused on Cuban tourism, will also draw on her expertise.

Findings

This paper addresses the Cuban Government’s ongoing response to the COVID-19 pandemic and places this response in the context of Cuba’s medical system, its health tourism and related diplomacy. It reveals key lessons from Cuba’s response for other tourist destination states and, more broadly, for the worldwide response to global outbreaks and the management of health systems. The findings will further research in diplomacy and tourism as well as inform policy and practice.

Research limitations/implications

This paper explores an ongoing topic and thus further research will be required following the pandemic.

Practical implications

This research note offers important implications for practice including providing accurate, research-based information that challenges misinformation about Cuba’s health system, its medical diplomacy program, health tourism and its response to COVID-19. It offers valuable lessons for public health authorities including the importance of preventative health measures, community medicine and the benefits of working globally to combat outbreaks through the sharing of medical staff and resources.

Social implications

This research note reveals the health, political and social implications of Cuba’s response in this time of crisis. It shows the benefits of a robust but low-cost community-based medicine program, medical diplomacy and how a state’s response during crisis can moderate the global inequities and injustices such as unequal access to care that often accompany disease outbreaks such as COVID-19.

Originality/value

This research note is an early analysis of a response by an important tourist destination country to the pandemic. The author anticipates that the information provided to the international community via this open access journal will offer practical implications for the ongoing global efforts to manage this crisis and contribute to the research on tourism, diplomacy, justice and health policy.
Clearing gang- and drug-involved nonfatal shootings
Authors: Barao Lisa , Braga Anthony A. , Turchan Brandon , Cook Philip J.
Published: March 2021

Purpose

Clearance rates for nonfatal shootings, especially cases involving gang- and drug-related violence, are disturbingly low in many US cities. Using data from a previously completed project in Boston, we explore the prospects for improving gang/drug nonfatal shooting cases by investing the same investigative effort found in similar gang/drug gun murder cases.

Design/methodology/approach

Our analyses primarily focus on a sample of 231 nonfatal shootings that occurred in Boston from 2010 to 2014. Logistic regressions are first used to analyze differences in the likelihood of case clearance for gang/drug nonfatal shooting cases relative to other nonfatal shooting cases. Independent samples t-tests are then used to compare the investigative characteristics of these two different kinds of nonfatal shootings. Next, independent samples t-tests are used to compare the investigation of gang/drug gun assaults relative to the investigation of very similar gang/drug gun homicides.

Findings

Results demonstrate that the odds of clearing gang/drug nonfatal shootings are 77.2% less likely relative to the odds of clearing nonfatal shootings resulting from other circumstances. This stark difference in clearance rates is not driven by diminished investigative effort, but investigative effort does matter. Relative to gang/drug gun assaults, gang/drug gun homicides have much higher clearance rates that are the result of greater investigative resources and effort that produces significantly more witnesses and evidence, and generate more forensic tests and follow-up investigative actions.

Originality/value

Gang- and drug-related violence generates a bulk of urban nonfatal shootings. Low clearance rates for nonfatal shootings undermine police efforts to hold offenders accountable, disrupt cycles of gun violence, and provide justice to victims. Police should make investments to improve investigative effort such as handling these cases with the same vigor as homicide cases.
Tourism service providers’ physical attractiveness and customers’ service quality evaluation: is warmth or competence more important?
Authors: Li Yaoqi , Liu Biqiang , Chen Ping , Huan Tzung-Cheng
Published: March 2021

Purpose

This paper aims to introduce the psychological variable of “social distance” and use SEM to analyze the relationship between tourism service providers’ physical attractiveness (SPPA) and tourists’ perceptions of social distance, stereotypes and service quality.

Design/methodology/approach

The data collectors were instructed to convenience sampling tourists in Guangzhou Chimelong Tourist Resort, the biggest resort in South China and 334 valid questionnaires were collected. This study used CFA to confirm the measurement model and to check the reliability and validity of the constructs. Using Mplus 7.0, SEM was performed to test the hypotheses of this study.

Findings

The study found that tourism SPPA can improve tourists’ stereotype perception by reducing the social distance between tourists and service providers, which ultimately improves service quality. This study also found that only warmth perception can significantly improve the service quality evaluation of tourists, with competence perception having no significant effect.

Originality/value

This study focused on the SPPA in tourism services, expanding the research on tourism service management and on the effect of physical attractiveness; enriched the stereotype content model and behaviors from intergroup affect and stereotypes map by clarifying the mediating role of social distance and stereotypes; found different roles played by the competence and warmth stereotype in the enhancement effect; helped find an insightful strategy to improve service quality by recruiting and training employees intentionally.