bluuebunny/crossref_metadata_2025 huggingface dataset:
Variance Reducing and Noise Correction in Protein Quantification by Measuring Fluctuations in Fluorescence due to Photobleaching
Authors: Gelber Itay
Published: June 2021

Quantifying protein number using the ratio between the variance and the mean of the protein distribution is a straightforward calibration method in the experimental conditions for microscopy imaging. Recently the model has been expanded to decaying processes with binomial distribution. In this paper, we examine the model proposed, and show how the algorithm can be adapted to the case of variance in the initial number of proteins between cells. We propose improving the algorithm so that the information processing of each frame is done independently from other frames. By doing so, the variance in the process of determining the protein number can be reduced. In addition, we examine the handling of unwanted noises in the measurement, offer a solution for shot noise and background noise, and examine the expected error caused in calculating the decay constant. We also analyze the expected difficulties in conducting a practical experiment, which includes non-exponential decay, and variance in the decay constants of the cells. These methods can be applied to any superposition of n0 discrete decaying processes. However, the evaluation of expected errors in quantification is essential for early planning of the experimental conditions, and for the evaluation of the error.
Expansion of RNA sequence diversity and RNA editing rates throughout human cortical development
Authors: Cuddleston Ryn , Sloofman Laura , Liang Lindsay , Mossotto Enrico , Fan Xuanjia , Wang Minghui , Zhang Bin , Wang Jiebiao , Sestan Nenad , Devlin Bernie , Roeder Kathryn , Buxbaum Joseph D. , Sanders Stephan J. , Breen Michael S.
Published: June 2021

Post-transcriptional modifications by RNA editing are essential for neurodevelopment, yet their developmental and regulatory features remain poorly resolved. We constructed a full temporal view of base-specific RNA editing in the developing human cortex, from early progenitors through fully mature cells found in the adult brain. Developmental regulation of RNA editing is characterized by an increase in editing rates for more than 10,000 selective editing sites, shifting between mid-fetal development and infancy, and a massive expansion of RNA hyper-editing sites that amass in the cortex through postnatal development into advanced age. These sites occur disproportionally in 3’UTRs of essential neurodevelopmental genes. These profiles are preserved in non-human primate and murine models, illustrating evolutionary conserved regulation of RNA editing in mammalian cortical development. RNA editing levels are commonly genetically regulated (editing quantitative trait loci, edQTLs) consistently across development or predominantly during prenatal or postnatal periods. Both consistent and temporal-predominant edQTLs co-localize with risk loci associated with neurological traits and disorders, including attention deficit hyperactivity disorder, schizophrenia, and sleep disorders. These findings expand the repertoire of highly regulated RNA editing sites in the brain and provide insights of how epitranscriptional sequence diversity by RNA editing contributes to neurodevelopment.
BRN2 and PTN unveil multiple neurodevelopmental mechanisms in Schizophrenia patient-derived cerebral organoids
Authors: Notaras Michael , Lodhi Aiman , Dundar Friederike , Collier Paul , Sayles Nicole , Tilgner Hagen , Greening David , Colak Dilek
Published: June 2021

Due to an inability to ethically access developing human brain tissue as well as identify prospective cases, early-arising neurodevelopmental and cell-specific signatures of Schizophrenia (Scz) have remained unknown and thus undefined. To overcome these challenges, we utilized Scz patient-derived stem cells to generate 3D cerebral organoids to model neuropathology of Scz during this critical period. We discovered that Scz organoids exhibited ventricular neuropathology resulting in altered progenitor survival and disrupted neurogenesis. This ultimately yielded fewer neurons within developing cortical fields of Scz organoids. Single-cell sequencing revealed that Scz progenitors were specifically depleted of neuronal programming factors leading to a remodeling of cell-lineages, altered differentiation trajectories, and distorted cortical cell-type diversity. While Scz organoids were 99.95% similar in their macromolecular diversity to Ctrls, four GWAS factors (PTN, COMT, PLCL1, and PODXL) and peptide fragments belonging to the POU-domain transcription factor family (e.g. POU3F2/BRN2) were altered. This revealed that Scz organoids principally differed not in their proteomic diversity, but specifically in their total quantity of disease and neurodevelopmental factors at the molecular level. Single-cell sequencing also subsequently identified cell-type specific alterations in neuronal programming factors and growth factors, and specifically replicated the depletion of POU3F2 (BRN2) and PTN in both Scz progenitors and neurons. Consequently, in two mechanistic rescue experiments we identified that the transcription factor POU3F2 (BRN2) and growth factor PTN operate as mechanistic substrates of neurogenesis and cellular survival, respectively, in Scz organoids. This suggests that multiple mechanisms of Scz exist in patient-derived organoids, and that these disparate mechanisms converge upon primordial brain developmental pathways such as neuronal differentiation, survival, and growth factor support, which may amalgamate to elevate intrinsic risk of Scz.
MPI8 is Potent Against SARS-CoV-2 by Inhibiting Dually and Selectively the SARS-CoV-2 Main Protease and the Host Cathepsin L
Authors: Ma Xinyu R. , Alugubelli Yugendar R. , Ma Yuying , Vantasever Erol C. , Scott Danielle A. , Qiao Yuchen , Yu Ge , Xu Shiqing , Liu Wenshe Ray
Published: June 2021

A number of inhibitors have been developed for the SARS-CoV-2 main protease (MPro) as potential COVID-19 medications but little is known about their selectivity. Using enzymatic assays, we characterized inhibition of TMPRSS2, furin, and cathepsins B/K/L by more than a dozen of previously developed MPro inhibitors including MPI1-9, GC376, 11a, 10-1, 10-2, and 10- 3. MPI1-9, GC376 and 11a all contain an aldehyde for the formation of a reversible covalent hemiacetal adduct with the MPro active site cysteine and 10-1, 10-2 and 10-3 contain a labile ester to exchange with the MPro active site cysteine for the formation of a thioester. Our data revealed that all these inhibitors are inert toward TMPRSS2 and furin. Diaryl esters also showed low inhibition of cathepsins. However, all aldehyde inhibitors displayed high potency in inhibiting three cathepsins. Their determined IC50 values vary from 4.1 to 380 nM for cathepsin B, 0.079 to 2.3 nM for cathepsin L, and 0.35 to 180 nM for cathepsin K. All aldehyde inhibitors showed similar inhibition levels toward cathepsin L. A cellular analysis indicated high potency of MPI5 and MPI8 in inhibiting lysosomal activity, which is probably attributed to their inhibition of cathepsins. Among all aldehyde inhibitors, MPI8 shows the best selectivity toward cathepsin L. With respect to cathepsins B and K, the selective indices are 192 and 150, respectively. MPI8 is the most potent compound among all aldehyde inhibitors in cellular MPro inhibition potency and anti-SARS-CoV-2 activity in Vero E6 cells. Cathepsin L has been demonstrated to play a critical role in the SARS-CoV-2 cell entry. By selectively inhibiting both SARS-CoV-2 MPro and the host cathepsin L, MPI8 potentiates dual inhibition effects to synergize its overall antiviral potency and efficacy. Due to its high selectivity toward cathepsin L that reduces potential toxicity toward host cells and high cellular and antiviral potency, we urge serious consideration of MPI8 for preclinical and clinical investigations for treating COVID-19.
A midbody component homolog, too much information/prc1-like, is required for microtubule reorganization during both cytokinesis and axis induction in the early zebrafish embryo
Authors: Nair S , Welch E.L. , Moravec C.E. , Trevena R.L. , Pelegri F.
Published: June 2021

We show that the zebrafish maternal-effect mutation too much information (tmi) corresponds to zebrafish prc1-like (prc1l), which encodes a member of the MAP65/Ase1/PRC1family of microtubule-associated proteins. Embryos from tmi/prc1l homozygous mutant mothers display cytokinesis defects in meiotic and mitotic divisions in the early embryo, indicating that tmi/prc1l has a role in midbody formation during cell division at the egg-to-embryo transition. Unexpectedly, maternal tmi/prc1l function is also essential for the reorganization of vegetal pole microtubules required for embryonic axis induction. While Prc1 is widely regarded to crosslink microtubules in an antiparallel conformation, our studies provide evidence for an additional function of Prc1 in the bundling of parallel microtubules in the vegetal cortex of the early embryo during cortical rotation and prior to mitotic cycling. These findings highlight common yet distinct aspects of microtubule reorganization that occur during the egg-to-embryo transition, driven by maternal product for the midbody component Prc1l and required for embryonic cell division and pattern formation.
Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells
Authors: Calandrelli Riccardo , Wen Xingzhao , Charles Richard John Lalith , Luo Zhifei , Nguyen Tri C. , Chen Chien-Ju , Qi Zhijie , Xue Shuanghong , Chen Weizhong , Yan Zhangming , Wu Weixin , Zaleta-Rivera Kathia , Hu Rong , Yu Miao , Wang Yuchuan , Li Wenbo , Ma Jian , Ren Bing , Zhong Sheng
Published: June 2021

The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether the genome architecture modulates the spatial distribution of caRNA and vice versa. Here, we generate a resource of genome-wide RNA-DNA and DNA-DNA contact maps in human cells. These maps reveal the chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined chromosomal domains. Further, the spreading of caRNA is constrained by the boundaries of topologically associating domains (TADs), demonstrating the role of the 3D genome structure in modulating the spatial distribution of RNA. Conversely, stopping transcription or acute depletion of RNA induces thousands of chromatin loops genome-wide. Activation or suppression of the transcription of specific genes suppresses or creates chromatin loops straddling these genes. Deletion of a specific caRNA-producing genomic sequence promotes chromatin loops that straddle the interchromosomal target sequences of this caRNA. These data suggest a feedback loop where the 3D genome modulates the spatial distribution of RNA, which in turn affects the dynamic 3D genome organization.
A Novel Local Ablation Approach for Explaining Multimodal Classifiers
Authors: Ellis Charles A. , Carbajal Darwin A. , Zhang Rongen , Sendi Mohammad S.E. , Miller Robyn L. , Calhoun Vince D. , Wang May D.
Published: June 2021

With the growing use of multimodal data for deep learning classification in healthcare research, more studies have begun to present explainability methods for insight into multimodal classifiers. Among these studies, few have utilized local explainability methods, which could provide (1) insight into the classification of each sample and (2) an opportunity to better understand the effects of demographic and clinical variables within datasets (e.g., medication of subjects in electrophysiology data). To the best of our knowledge, this opportunity has not yet been explored within multimodal classification. We present a novel local ablation approach that shows the importance of each modality to the correct classification of each class and explore the effects of demographic and clinical variables upon the classifier. As a use-case, we train a convolutional neural network for automated sleep staging with electroencephalogram (EEG), electrooculogram (EOG), and electromyogram (EMG) data. We find that EEG is the most important modality across most stages, though EOG is particular important for non-rapid eye movement stage 1. Further, we identify significant relationships between the local explanations and subject age, sex, and state of medication which suggest that the classifier learned specific features associated with these variables across multiple modalities and correctly classified samples. Our novel explainability approach has implications for many fields involving multimodal classification. Moreover, our examination of the degree to which demographic and clinical variables may affect classifiers could provide direction for future studies in automated biomarker discovery.
A putative de novo evolved gene required for spermatid chromatin condensation in Drosophila melanogaster
Authors: Rivard Emily L. , Ludwig Andrew G. , Patel Prajal H. , Grandchamp Anna , Arnold Sarah E. , Berger Alina , Scott Emilie M. , Kelly Brendan J. , Mascha Grace C. , Bornberg-Bauer Erich , Findlay Geoffrey D.
Published: June 2021

Comparative genomics has enabled the identification of genes that potentially evolved de novo from non-coding sequences. Many such genes are expressed in male reproductive tissues, but their functions remain poorly understood. To address this, we conducted a functional genetic screen of over 40 putative de novo genes with testis-enriched expression in Drosophila melanogaster and identified one gene, atlas, required for male fertility. Detailed genetic and cytological analyses showed that atlas is required for proper chromatin condensation during the final stages of spermatogenesis. Atlas protein is expressed in spermatid nuclei and facilitates the transition from histone- to protamine-based chromatin packaging. Complementary evolutionary analyses revealed the complex evolutionary history of atlas. The protein-coding portion of the gene likely arose at the base of the Drosophila genus on the X chromosome but was unlikely to be essential, as it was then lost in several independent lineages. Within the last ∼15 million years, however, the gene moved to an autosome, where it fused with a conserved non-coding RNA and evolved a non-redundant role in male fertility. Altogether, this study provides insight into the integration of novel genes into biological processes, the links between genomic innovation and functional evolution, and the genetic control of a fundamental developmental process, gametogenesis.

Author Summary

Genomes are in flux, as genes are constantly added and lost throughout evolution. New genes were once thought to arise almost exclusively via the modification or duplication of existing genes. Recently, however, interest has grown in alternative modes of new gene origination, such as de novo evolution from genetic material that previously did not encode proteins. Many de novo genes are expressed in male reproductive tissues, but their significance for fertility is not well understood. We screened likely de novo genes expressed in the Drosophila testis for reproductive roles and found one gene, atlas, essential for male fertility. We leveraged genetic and cell biological experiments to investigate roles for Atlas protein in reproduction and found that it is required during sperm development for proper packaging of DNA in the sperm nucleus. Evolutionary analyses of this gene revealed a complicated history, including loss in some lineages, movement between chromosomes, and fusion with a non-protein-coding gene. Studying both the functions and evolutionary histories of new proteins illustrates how they might evolve critical roles in biological processes despite their relative novelty. Furthermore, the study of atlas identifies an essential genetic player in the fly testis, an important model system for understanding how gametes are produced.
Exploiting node metadata to predict interactions in large networks using graph embedding and neural networks
Authors: Runghen Rogini , Stouffer Daniel B , Dalla Riva Giulio V
Published: June 2021

Collecting network interaction data is difficult. Non-exhaustive sampling and complex hidden processes often result in an incomplete data set. Thus, identifying potentially present but unobserved interactions is crucial both in understanding the structure of large scale data, and in predicting how previously unseen elements will interact. Recent studies in network analysis have shown that accounting for metadata (such as node attributes) can improve both our understanding of how nodes interact with one another, and the accuracy of link prediction. However, the dimension of the object we need to learn to predict interactions in a network grows quickly with the number of nodes. Therefore, it becomes computationally and conceptually challenging for large networks. Here, we present a new predictive procedure combining a graph embedding method with machine learning techniques to predict interactions on the base of nodes’ metadata. Graph embedding methods project the nodes of a network onto a—low dimensional—latent feature space. The position of the nodes in the latent feature space can then be used to predict interactions between nodes. Learning a mapping of the nodes’ metadata to their position in a latent feature space corresponds to a classic—and low dimensional—machine learning problem. In our current study we used the Random Dot Product Graph model to estimate the embedding of an observed network, and we tested different neural networks architectures to predict the position of nodes in the latent feature space. Flexible machine learning techniques to map the nodes onto their latent positions allow to account for multivariate and possibly complex nodes’ meta-data. To illustrate the utility of the proposed procedure, we apply it to a large dataset of tourist visits to destinations across New Zealand. We found that our procedure accurately predicts interactions for both existing nodes and nodes newly added to the network, while being computationally feasible even for very large networks. Overall, our study highlights that by exploiting the properties of a well understood statistical model for complex networks and combining it with standard machine learning techniques, we can simplify the link prediction problem when incorporating multivariate node metadata. Our procedure can be immediately applied to different types of networks, and to a wide variety of data from different systems. As such, both from a network science and data science perspective, our work offers a flexible and generalisable procedure for link prediction.
Mitochondrial COA7 is a heme-binding protein involved in the early stages of complex IV assembly
Authors: Formosa Luke E. , Maghool Shadi , Sharpe Alice J. , Reljic Boris , Muellner-Wong Linden , Stroud David A. , Ryan Michael T. , Maher Megan J.
Published: June 2021

Cytochrome c oxidase assembly factor 7 (COA7) is a metazoan-specific assembly factor, critical for the biogenesis of mitochondrial complex IV (cytochrome c oxidase). Although mutations in COA7 have been linked in patients to complex IV assembly defects and neurological conditions such as peripheral neuropathy, ataxia and leukoencephalopathy, the precise role COA7 plays in the biogenesis of complex IV is not known. Here we show that the absence of COA7 leads to arrest of the complex IV assembly pathway at the initial step where the COX1 module is built, which requires incorporation of copper and heme cofactors. In solution, purified COA7 binds heme with micromolar affinity, through axial ligation to the central iron atom by histidine and methionine residues. Surprisingly, the crystal structure of COA7, determined to 2.4 Å resolution, reveals a ‘banana-shaped’ molecule composed of five helix-turn-helix (α/α) repeats, tethered by disulfide bonds, with a structure entirely distinct from proteins with characterized heme binding activities. We therefore propose a role for COA7 in heme binding/chaperoning in the mitochondrial intermembrane space, this activity being crucial for and providing a missing link in complex IV biogenesis.

Significance Statement

Assembly factors play key roles in the biogenesis of many mitochondrial protein complexes regulating their stability, activity and incorporation of essential cofactors. COA7 is a metazoan-specific assembly factor, the absence or mutation of which in humans accompanies complex IV assembly defects and neurological conditions. Here we report the crystal structure of COA7 to 2.4 Å resolution, revealing a ‘banana-shaped’ molecule composed of five helix-turn-helix (α/α) repeats, tethered by disulfide bonds. Characterization of pathogenic variants reveals significantly lower stabilities, correlating with the associated disease outcomes. Fascinatingly, COA7 binds heme with micromolar affinity, despite the fact that the protein structure does not resemble previously characterized heme-binding proteins. This provides a possible missing link for heme handling in the mitochondrial intermembrane space.
MKP-1 modulates Ubiquitination/Phosphorylation of TLR signaling
Authors: Talreja Jaya , Bauerfeld Christian , Wang Xiantao , Hafner Markus , Liu Yusen , Samavati Lobelia
Published: June 2021

Ubiquitination and phosphorylation are reversible post-translational protein modifications regulating physiological and pathological processes. MAPK phosphatase (MKP)-1 regulates innate and adaptive immunity. The multifaceted roles of MKP-1 were attributed to dephosphorylation of p38 and JNK mitogen activated kinases (MAPKs). We show that the lack of MKP-1 modulates the landscape of ubiquitin ligases and deubiquitinase enzymes (DUBs). MKP-1 deficient mice showed an aberrant regulation of several DUBs and increased expression of proteins and genes involved in IL-1/TLR signaling upstream of MAPK, including IL-1R1, IRAK1, TRAF6, phosphorylated TAK1 and an increased K63-polyubiquitination on TRAF6. Increased K63-polyubiquitination on TRAF6 was associated with an enhanced phosphorylated form of A20. Among abundant DUBs, Ubiquitin-specific-protease-13 (USP13), which cleaves polyubiquitin- chains on client proteins, was substantially enhanced in murine MKP-1 deficient BMDMs. An inhibitor of USP13 decreased the K63-polyubiquitination on TRAF6, TAK1-phosphorylation, IL-1β and TNF-α induction in response to LPS in BMDMs. Our data show for the first time that MKP-1 modulates the ligase activity of TRAF6 through modulation of specific DUBs.
Sustained mechanical tension governs fibrogenic activation of tendon stromal cells in systemic sclerosis
Authors: Hussien Amro A. , Knell Robert , Renoux Florian , Wunderli Stefania L. , Niederoest Barbara , Foolen Jasper , Distler Oliver , Snedeker Jess G.
Published: June 2021

Fibrosis is a pathological outcome of aberrant repair responses in systemic sclerosis and affects many tissues, including tendons. Progressive matrix stiffening is a key feature of this pathological remodeling. How dysregulated tissue mechanics contribute to the persistence of the fibrotic phenotype has been obscured by limited availability of experimental tissue models that are both controllable and capture essential aspects of the tendon biophysical niche. Here, we developed a modular, cantilever-based platform that allows culture of 3D tendon-like constructs under easily variable static tension, emulating this central tendon-specific structure function relationship. The system reveals that elevated matrix tension instigates fibroblast-to-myofibroblast activation eliciting scar-like phenotypes in vitro. By using this mechano-culture system and preclinical and clinical models of systemic sclerosis, we further show that 3D matrix stiffness is inversely correlated with the transcription of major pro-fibrotic collagens, but positively correlate with the expression of markers of stromal-immune interactions. Co-culture of tendon stromal fibroblasts and bone marrow-derived macrophages override stiffness-mediated downregulation of matrix transcription, suggesting that normal tension mediated checkpoints are superseded by the local tissue immune state. Our study highlights the power of 3D reductionist approaches in dissecting the contribution of the elevated matrix tension to the positive feedforward loops between activated fibroblasts and progressive ECM stiffening in systemic sclerosis.
A high-quality functional genome assembly of Delia radicum L. (Diptera: Anthomiidae) annotated from egg to adult
Authors: Sontowski Rebekka , Poeschl Yvonne , Okamura Yu , Vogel Heiko , Guyomar Cervin , Cortesero Anne-Marie , van Dam Nicole M.
Published: June 2021

Belowground herbivores are overseen and underestimated, even though they can cause significant economic losses in agriculture. The cabbage root fly Delia radicum (Anthomyiidae) is a common pest in Brassica species, including agriculturally important crops, such as oil seed rape. The damage is caused by the larvae, which feed specifically on the taproots of Brassica plants until they pupate. The adults are aboveground-living generalists feeding on pollen and nectar. Female flies are attracted by chemical cues in Brassica plants for oviposition. An assembled and annotated genome can elucidate which genetic mechanisms underlie the adaptation of D. radicum to its host plants and their specific chemical defenses, in particular isothiocyanates. Therefore, we assembled, annotated and analyzed the D. radicum genome using a combination of different Next Generation Sequencing and bioinformatic approaches. We assembled a chromosome-level D. radicum genome using PacBio and Hi-C Illumina sequence data. Combining Canu and 3D-DNA genome assembler, we constructed a 1.3 Gbp genome with an N50 of 242 Mbp and 6 pseudo-chromosomes. To annotate the assembled D. radicum genome, we combined homology-, transcriptome- and ab initio-prediction approaches. In total, we annotated 13,618 genes that were predicted by at least two approaches. We analyzed egg, larval, pupal and adult transcriptomes in relation to life-stage specific molecular functions. This high-quality annotated genome of D. radicum is a first step to understanding the genetic mechanisms underlying host plant adaptation. As such, it will be an important resource to find novel and sustainable approaches to reduce crop losses to these pests.
The asymmetric Pitx2 regulates intestinal muscular-lacteal development and protects against fatty liver disease
Authors: Hu Shing , Mahadevan Aparna , Elysee Isaac F. , Choi Joseph , Souchet Nathan R. , Bae Gloria H. , Taboada Alessandra K. , Duhamel Gerald E. , Sevier Carolyn S. , Tao Ge , Kurpios Natasza A.
Published: June 2021

Intestinal lacteals are the essential lymphatic channels for absorption and transport of dietary lipids and drive pathogenesis of debilitating metabolic diseases. Yet, organ-specific mechanisms linking lymphatic dysfunction to disease etiology remain largely unknown. In this study, we uncover a novel intestinal lymphatic program that is linked to the left-right (LR) asymmetric transcription factor Pitx2. We show that deletion of the asymmetric Pitx2 enhancer, ASE, alters normal lacteal development through the lacteal-associated contractile smooth muscle lineage. ASE deletion leads to abnormal muscle morphogenesis induced by oxidative stress, resulting in impaired lacteal extension and defective lymphatic-dependent lipid transport. Surprisingly, activation of lymphatic-independent trafficking directs dietary lipids from the gut directly to the liver, causing diet-induced fatty liver disease. In summary, our studies reveal the molecular mechanism linking gut lymphatic development to the earliest symmetry-breaking Pitx2 and highlight the important relationship between intestinal lymphangiogenesis and gut-liver axis.

GRAPHICAL ABSTRACT

HIGHLIGHTS

∼ Gut lymphangiogenesis is linked to Pitx2-driven LR asymmetry

∼ Lacteal-associated smooth muscle requires ASE

∼ ASE deletion leads to redox imbalance in intestinal smooth muscle lineage

∼ ASE is required for the normal route of dietary lipid transport

∼ Pitx2ASE/ASE neonates develop diet-induced fatty liver disease
High-level language brain regions are sensitive to sub-lexical regularities
Authors: Regev Tamar I. , Affourtit Josef , Chen Xuanyi , Schipper Abigail E. , Bergen Leon , Mahowald Kyle , Fedorenko Evelina
Published: June 2021

A network of left frontal and temporal brain regions supports ‘high-level’ language processing— including the processing of word meanings, as well as word-combinatorial processing—across presentation modalities. This ‘core’ language network has been argued to store our knowledge of words and constructions as well as constraints on how those combine to form sentences. However, our linguistic knowledge additionally includes information about sounds (phonemes) and how they combine to form clusters, syllables, and words. Is this knowledge of phoneme combinatorics also represented in these language regions? Across five fMRI experiments, we investigated the sensitivity of high-level language processing brain regions to sub-lexical linguistic sound patterns by examining responses to diverse nonwords—sequences of sounds/letters that do not constitute real words (e.g., punes, silory, flope). We establish robust responses in the language network to visually (Experiment 1a, n=605) and auditorily (Experiments 1b, n=12, and 1c, n=13) presented nonwords relative to baseline. In Experiment 2 (n=16), we find stronger responses to nonwords that obey the phoneme-combinatorial constraints of English. Finally, in Experiment 3 (n=14) and a post-hoc analysis of Experiment 2, we provide suggestive evidence that the responses in Experiments 1 and 2 are not due to the activation of real words that share some phonology with the nonwords. The results suggest that knowledge of phoneme combinatorics and representations of sub-lexical linguistic sound patterns are stored within the same fronto-temporal network that stores higher-level linguistic knowledge and supports word and sentence comprehension.
Distinct neural dynamics underlie the encoding of visual speed in stationary and running mice
Authors: Horrocks Edward A B , Saleem Aman B
Published: June 2021

Sensory experiences are often driven by an animal’s self-motion and locomotion is known to modulate neural responses in the mouse visual system. This modulation is hypothesised to improve the processing of behaviourally relevant visual inputs, which may change rapidly during locomotion. However, little is known about how locomotion modulates the temporal dynamics (time courses) of visually-evoked neural responses. Here, we analysed the temporal dynamics of single neuron and population responses to dot field stimuli moving at a range of visual speeds using the Visual Coding dataset from the Allen Institute for Brain Science1. Single neuron responses had diverse temporal dynamics that varied between stationary and running sessions. Increased dynamic range and more reliable responses in running sessions enabled faster, stronger and more persistent encoding of visual speed. Population activity reflected the temporal dynamics of single neuron responses, including their modulation by locomotor state - neural trajectories of population activity made more direct transitions between baseline and stimulus steady states in running sessions. The structure of population coding also changed with locomotor state – population activity prioritised the encoding of visual speed in running, but not stationary sessions. Our results reveal a profound influence of locomotion on the temporal dynamics of neural responses. We demonstrate that during locomotion, mouse visual areas prioritise the encoding of potentially fast-changing, behaviourally relevant visual features.
The role of hub neurons in modulating cortical dynamics
Authors: Gal Eyal , Amsalem Oren , Schindel Alon , London Michael , Schürmann Felix , Markram Henry , Segev Idan
Published: June 2021

Many neurodegenerative diseases are associated with the death of specific neuron types in particular brain regions. What makes the death of specific neuron types particularly harmful for the integrity and dynamics of the respective network is not well understood. To start addressing this question we used the most up-to-date biologically-realistic dense neocortical microcircuit (NMC) of rodent, which has reconstructed a volume of 0.3 mm3 and containing 31,000 neurons, 36 million synapses, and 55 morphological cell types arranged in 6 cortical layers. Using modern network science tools, we identified “hub-neurons” in the NMC, that are connected synaptically to a large number of their neighbors and systematically examined the impact of abolishing these cells. In general, the structural integrity of the network is robust to cells’ attack; yet, attacking hub neurons strongly impacted the “small worldness” topology of the network, whereas similar attacks on random neurons have a negligible effect. Such hub-specific attacks are also impactful on the network dynamics, both when the network is at its spontaneous synchronous state and when it was presented with synchronized thalamo-cortical visual-like input. We found that attacking layer 5 hub neurons are most harmful to the structural and functional integrity of the NMC. The significance of our results for understanding the role of specific neuron types and cortical layers for disease manifestation is discussed.
[(1,2,5,6-η)-Cycloocta-1,5-diene](1-ethyl-3-isopropyl-1,3-imidazol-2-ylidene)(triphenylphosphane)rhodium(I) tetrafluoridoborate
Authors: Rood Jeffrey A. , Subedi Chhatra B. , Risell John P. , Astashkin Andrei V. , Rajaseelan Edward
Published: June 2021

A new N-heterocyclic cationic rhodium(I) complex with a tetrafluoridoborate counter-anion, [Rh(C8H14N2)(C8H12)(C18H15P)]BF4, has been prepared and structurally characterized. The cationic complex exhibits a distorted square-planar environment around the rhodium(I) ion. Two connections are made from rhodium(I) to the carbon atom of an N-heterocylic carbene ligand and to the phosphorus atom of a triphenylphosphane ligand. The remaining two coordination sites are made via a bidentate interaction from the two olefinic bonds of cyclooctadiene to the rhodium(I) ion. The compound includes an out-sphere tetrafluoridoborate counter-anion. Within the crystal of the compound exist several weak intermolecular C—H...F interactions.
Supply chain dynamics, big data capability and product performance
Authors: Lin Canchu , Kunnathur Anand , Forrest Jeffrey
Published: June 2021

Purpose

The purpose of this study is to examine big data capability's impact on product improvement and explore supply chain dynamics including relationship building and knowledge sharing as important contribution to big data capability.

Design/methodology/approach

The research model is tested with survey data. Data analysis results empirically support the proposed model and the hypothesized relationships between the concepts.

Findings

First, the hypothesis testing results of this study show that big data capability directly enhances product improvement. Second, this study shows that supply chain relationship building and knowledge sharing are positively related to the development of big data capability.

Research limitations/implications

In supply chain management, there are multiple factors, besides relationship building, that serve as conditioners to knowledge sharing's effect on product performance. We only examined the role of relationship building in this area.

Practical implications

Findings from this research encourage firms to take advantage of their supply chain resources to develop a big data capability that positively contributes to firm performance.

Originality/value

The contribution lies in that it brings to light this step that connects big data capabilities and market and financial performance, which is missing in prior research. This study contributes to the literature by identifying supply chain management activities, more specifically, supply chain relationship building and knowledge sharing, as antecedents to big data capability. This helps to extend this emergent enterprise of big data research to a new area and points to new directions for future research.
The meso-failure mechanism of lightweight concrete simulated by the phase field method
Authors: Wang Jichang , Guo Xiaoming
Published: June 2021

Purpose

A mesoscopic phase field (PF) model is proposed to simulate the meso-failure process of lightweight concrete.

Design/methodology/approach

The PF damage model is applied to the meso-failure process of lightweight concrete through the ABAQUS subroutine user-defined element (UEL). And the improved staggered iteration scheme with a one-pass procedure is used to alternately solve the coupling equations.

Findings

These examples clearly show that the crack initiation of the lightweight concrete specimens mainly occurs in the ceramsite aggregates with weak strength, especially in the larger aggregates. The crack propagation paths of the specimens with the same volume fraction of light aggregates are completely different, but the crack propagation paths all pass through the ceramsite aggregates near the cracks. The results also showed that with the increase in the volume fractions of the aggregates, the slope and the peak loads of the force-deflection (F-d) curves gradually decrease, the load-bearing capacity of the lightweight concrete specimens decreases, and crack branching and coalescence are less likely during crack propagation.

Originality/value

The mesostructures with a mortar matrix, aggregates and an interfacial transition zone (ITZ) are generated by an automatic generation and placement program, thus incorporating the typical three-phase characteristics of lightweight concrete into the PF model.
Moving beyond the rhetoric on faculty diversity in higher education: an interview with diversity expert Dr Bailey Jackson
Authors: Gavino Monica C.
Published: June 2021

Purpose

The aim of this article is to provide Dr Bailey Jackson's perspective on institutional and systemic barriers to full inclusion of diverse faculty in higher education through the lens of the multicultural organizational development (MCOD) model. Dr Jackson is renowned for his work on social justice, diversity and multiculturalism.

Design/methodology/approach

This is a personal interview with Dr Bailey Jackson. This interview provides insight on institutional level change efforts through the MCOD framework, a perspective on why institutions get stuck on the way to becoming healthy multicultural institutions, and the effect on moving the needle on faculty diversity in institutions of higher education.

Findings

The institutional obstacles and barriers tend to be centered around misalignment with the mission, vision and core values, and how those are formulated to include diversity and inclusion. Faculty diversity is only one component in dealing with the health of any organization or the academy as a whole. If institutions focus on diversity faculty in an unhealthy system, they will encounter limitations on how much the institution will develop on the MCOD continuum. The health of the overall system is going to affect the approach to faculty diversity.

Practical implications

Dr Jackson provides insight on his work with the MCOD framework and specifically the overall health of the institution as critical to faculty diversity initiatives. Questions to help institutions begin to assess themselves and identify changes required to move toward Multicultural within the context of faculty diversity are provided.

Originality/value

Through a series of questions, insight from Dr Jackson on why institutions get stuck in moving the needle on faculty diversity through the lens of the MCOD framework is gained.
A synthetic indicator of market leaders in the crowdlending sector
Authors: Ribeiro-Navarrete Samuel , Palacios-Marqués Daniel , Martín Martín José María , Guaita Martínez José Manuel
Published: June 2021

Purpose

This study contributes to the limited literature on crowdlending by providing a data-driven analysis of the sector. A synthetic DP2 indicator is proposed to identify the leaders of the crowdlending market, the key factors behind their success and the medium-term competitive implications.

Design/methodology/approach

The study examines 17 crowdlending platforms and eight performance indicators. The information provided by these indicators is aggregated using a synthetic indicator based on theP2Distance (DP2) method.

Findings

Mintos, Evoestate, Peerberry, Bondster and Fellow Finance are the leading platforms. This method reveals the key variables in the identification of market leaders, namely year-on-year variation in the number of investors and year-on-year variation in lending per investor. The leaders in terms of lending volumes should not take their current situation for granted. Small and medium-sized platforms are pushing hard and may overtake the incumbents as market leaders.

Practical implications

Financial intermediation through crowdlending is becoming an increasingly popular alternative to traditional models. Changes in the sector are expected in the coming years due to the rise of platforms with a moderate amount of lending and solid year-on-year improvement. To become leaders and to attract both lenders and borrowers, platforms are encouraged to improve the information that they provide.

Originality/value

This paper offers the first analysis of market leadership in the crowdlending sector. It analyses the competitive market of the crowdlending sector based on its actors and key factors. These factors explain the differences in the market position of different platforms. Based on this analysis, the trends in this sector can be identified. This study is exploratory, so it offers empirical data that can be useful in the development of theories that apply to the sector.
Pharmacy service factors and pharmacy performance: the role of patient satisfaction in community pharmacies
Authors: Barghouth Dana , Al-Abdallah Ghaith M. , Abdallah Ayman Bahjat
Published: June 2021

Purpose

This study aims to examine the effects of pharmacy service factors (namely, medication teaching, service promptness, pharmacist attitudes, medication supply and pharmacy location) on patient satisfaction with community pharmacies in Jordan and to explore the effect of patient satisfaction on pharmacy performance.

Design/methodology/approach

Descriptive analytical methodology, with a quantitative approach using survey strategy was applied. The study population represented the whole population of Jordan (2.033 million households). Data were collected using an online questionnaire. A convenient quota sample of 1,000 respondents was targeted; 502 valid questionnaires were returned, representing an effective response rate of 50.2%. The study hypotheses were tested using path analysis.

Findings

The results showed that the service factors contributing most significantly to patient satisfaction in Jordan are medication supply, pharmacist attitudes, medication teaching and service promptness, in descending order of influence. Meanwhile, the effect of pharmacy location on patient satisfaction proved to be insignificant. In addition, patient satisfaction proved to have a highly positive impact on pharmacy performance.

Originality/value

This study addresses a debatable issue in the literature regarding the influence that pharmacy service factors can have on patient satisfaction. In addition, to the best of the researchers’ knowledge, this is the first study to explore the proposed effects in Jordan. It is also one of the first to investigate the effect of patient satisfaction on community pharmacy performance.
Performance evaluation in humanitarian operations based on the beneficiary perspective
Authors: Cardoso Brenda , Fontainha Tharcisio , Leiras Adriana , Cardoso Patricia Alcantara
Published: June 2021

Purpose

This paper aims to identify the main performance criteria for Humanitarian Operations (HOs) from the beneficiary perspective and to propose a taxonomy to support the evaluation of stakeholders.

Design/methodology/approach

The research conducts a Systematic Literature Review to identify the main criteria in HOs from the beneficiary's view. Also, we conduct an empirical study based on a survey and a case study to validate the findings in a real-life setting.

Findings

Considering 25 papers, the identified performance criteria were divided into six categories: health, housing, education, socioeconomic factors, care and risk and disaster management. The empirical discussion considered forty-four responses from beneficiaries, and the main criteria complained about were related to socioeconomic factors. In addition, a case study was developed that examines the perspective of the company responsible for the construction of the building to aid in understanding the areas of dissatisfaction noted by the residents.

Practical implications

The research contributes organized criteria to support the performance evaluation of organizations. It offers a structured basis for further discussion among academics and professionals about other performance evaluation topics, such as dashboards and the integration of indicators from different stakeholders.

Originality/value

Literature is scarce in questions of performance evaluation in HOs and the analysis of the beneficiary as the main client. Therefore, the paper contributes to both areas by evaluating HOs from the beneficiary's perspective.
The Global Goals: bringing education for sustainable development into US business schools
Authors: Landrum Nancy E.
Published: June 2021

Purpose

This paper aims to learn how sustainability and the circular economy were being integrated into the curriculum of a Dutch university and to transfer that knowledge back to a US university business school curriculum. Given the resistance toward integrating sustainability into the US business school curriculum, the Dutch university served as a role model for education for sustainable development.

Design/methodology/approach

This case study used ethnographic methods of participant observation over a four-month residency at the Dutch university.

Findings

Themes observed are as follows: success in the current context relied upon sustainability being integrated into the culture and lifestyle, legislative enforcement, a focus on urban sustainability, use of the Sustainable Development Goals (SDGs) and collaboration as a key to success. The course proposal shifted to a class on the SDGs which is broader, more inclusive, and interdisciplinary. The proposal to integrate circular economy into the US business school curriculum shifted to a class on the SDGs. It was determined that the SDGs presented a more amenable approach to introduce sustainability into the business school curriculum and meet the objectives of education for sustainable development.

Research limitations/implications

This case study is based upon the author’s experience at one university in the Netherlands. Limitations include the generalizability of the findings to another university as well as the question of transferability across cultures.

Practical implications

This case study offers one suggestion for integrating sustainability into the business school curriculum.

Social implications

Integrating sustainability into the business school curriculum through the SDGs might help overcome resistance.

Originality/value

The findings offer an alternative approach for integrating sustainability into the business school curriculum that is aligned with AACSB standards and which might face less resistance.