bluuebunny/crossref_metadata_2025 huggingface dataset:
Time cell encoding in deep reinforcement learning agents depends on mnemonic demands
Authors: Lin Dongyan , Richards Blake A.
Published: July 2021

The representation of “what happened when” is central to encoding episodic and working memories. Recently discovered hippocampal time cells are theorized to provide the neural substrate for such representations by forming distinct sequences that both encode time elapsed and sensory content. However, little work has directly addressed to what extent cognitive demands and temporal structure of experimental tasks affect the emergence and informativeness of these temporal representations. Here, we trained deep reinforcement learning (DRL) agents on a simulated trial-unique nonmatch-to-location (TUNL) task, and analyzed the activities of artificial recurrent units using neuroscience-based methods. We show that, after training, representations resembling both time cells and ramping cells (whose activity increases or decreases monotonically over time) simultaneously emerged in the same population of recurrent units. Furthermore, with simulated variations of the TUNL task that controlled for (1) memory demands during the delay period and (2) the temporal structure of the episodes, we show that memory demands are necessary for the time cells to encode information about the sensory stimuli, while the temporal structure of the task only affected the encoding of “what” and “when” by time cells minimally. Our findings help to reconcile current discrepancies regarding the involvement of time cells in memory-encoding by providing a normative framework. Our modelling results also provide concrete experimental predictions for future studies.
A coordinated function of lncRNA HOTTIP and miRNA-196b underpinning leukemogenesis by targeting Fas signaling
Authors: Singh Ajeet P. , Luo Huacheng , Matur Meghana , Eshelman Melanie , Sharma Arati , Huang Suming
Published: July 2021

MicroRNAs (miRNAs) may modulate more than 60% of human coding genes and act as negative regulators, while long non-coding RNAs (lncRNAs) regulate gene expression on multiple levels by interacting with chromatin, functional proteins, and RNAs such as mRNAs and microRNAs. However, the crosstalk between lncRNA HOTTIP and miRNAs in leukemogenesis remains elusive. Using combined integrated analyses of global miRNA expression profiling and state-of-the-art genomic analyses of chromatin such as ChIRP-seq., (genome wide HOTTIP binding analysis), ChIP-seq., and ATAC-seq., we found that miRNA genes are directly controlled by HOTTIP. Specifically, the HOX cluster miRNAs (miR-196a, miR-196b, miR-10a and miR-10b), located cis & trans, were most dramatically regulated and significantly decreased in HOTTIP-/- AML cells. HOTTIP bound to the miR-196b promoter, and HOTTIP deletion reduced chromatin accessibility and enrichment of active histone modifications at HOX cluster associated miRNAs in AML cells, while reactivation of HOTTIP restored miR gene expression and chromatin accessibility in the CTCF-boundary-attenuated AML cells. Inactivation of HOTTIP or miR-196b promotes apoptosis by altering the chromatin signature at the FAS promoter and increasing FAS expression. Transplantation of miR-196b knockdown MOLM13 cells in NSG mice increased overall survival compared to wild-type cells. Thus, HOTTIP remodels the chromatin architecture around miRNAs to promote their transcription, consequently repressing tumor suppressors and promoting leukemogenesis.
Nicotinic acid mononucleotide is an allosteric SARM1 inhibitor promoting axonal protection
Authors: Sasaki Yo , Zhu Jian , Shi Yun , Gu Weixi , Kobe Bostjan , Ve Thomas , DiAntonio Aaron , Milbrandt Jeffrey
Published: July 2021

SARM1 is an inducible NAD+ hydrolase that is the central executioner of pathological axon loss. Recently, we elucidated the molecular mechanism of SARM1 activation, demonstrating that SARM1 is a metabolic sensor regulated by the levels of NAD+ and its precursor, nicotinamide mononucleotide (NMN), via their competitive binding to an allosteric site within the SARM1 N-terminal ARM domain. In healthy neurons with abundant NAD+, binding of NAD+ blocks access of NMN to this allosteric site. However, with injury or disease the levels of the NAD+ biosynthetic enzyme NMNAT2 drop, increasing the NMN/ NAD+ ratio and thereby promoting NMN binding to the SARM1 allosteric site, which in turn induces a conformational change activating the SARM1 NAD+ hydrolase. Hence, NAD+ metabolites both regulate the activation of SARM1 and, in turn, are regulated by the SARM1 NAD+ hydrolase. This dual upstream and downstream role for NAD+ metabolites in SARM1 function has hindered mechanistic understanding of axoprotective mechanisms that manipulate the NAD+ metabolome. Here we reevaluate two methods that potently block axon degeneration via modulation of NAD+ related metabolites, 1) the administration of the NMN biosynthesis inhibitor FK866 in conjunction with the NAD+ precursor nicotinic acid riboside (NaR) and 2) the neuronal expression of the bacterial enzyme NMN deamidase. We find that these approaches not only lead to a decrease in the levels of the SARM1 activator NMN, but also an increase in the levels of the NAD+ precursor nicotinic acid mononucleotide (NaMN). We show that NaMN inhibits SARM1 activation, and demonstrate that this NaMN-mediated inhibition is important for the long-term axon protection induced by these treatments. Analysis of the NaMN-ARM domain co-crystal structure shows that NaMN competes with NMN for binding to the SARM1 allosteric site and promotes the open, autoinhibited configuration of SARM1 ARM domain. Together, these results demonstrate that the SARM1 allosteric pocket can bind a diverse set of metabolites including NMN, NAD+, and NaMN to monitor cellular NAD+ homeostasis and regulate SARM1 NAD+ hydrolase activity. The relative promiscuity of the allosteric site may enable the development of potent pharmacological inhibitors of SARM1 activation for the treatment of neurodegenerative disorders.

Highlights

NaMN binds to SARM1 N-terminal allosteric site and inhibits SARM1 NAD+ hydrolase

NaMN inhibits SARM1 activation by stabilizing its open, inactive structure

NMN deamidase promotes strong axonal protection by reducing NMN and increasing NaMN
BET protein inhibition regulates macrophage chromatin accessibility and microbiota-dependent colitis
Authors: O’Connor Michelle Hoffner , Berglind Ana , Kennedy Meaghan M. , Keith Benjamin P. , Lynch Zachary J. , Schaner Matthew R. , Steinbach Erin C. , Herzog Jeremy , Trad Omar K. , Jeck William R. , Arthur Janelle C. , Sartor R. Balfour , Furey Terrence S. , Sheikh Shehzad Z.
Published: July 2021

Introduction

In colitis, macrophage functionality is altered compared to homeostatic conditions. Loss of IL-10 signaling results in an inappropriate and chronic inflammatory response to bacterial stimulation. It remains unknown if inhibition of bromodomain and extra-terminal domain (BET) proteins alters usage of DNA regulatory elements responsible for driving inflammatory gene expression. We determined if the BET inhibitor, (+)-JQ1, could suppress inflammatory activation of macrophages in Il10-/- mice.

Methods

We performed ATAC-seq and RNA-seq on Il10-/- bone marrow-derived macrophages (BMDMs) cultured in the presence or absence of lipopolysaccharide (LPS) and with or without treatment with (+)-JQ1 and evaluated changes in chromatin accessibility and gene expression. Germ-free Il10-/- mice were treated with (+)-JQ1, colonized with fecal slurries and underwent histological and molecular evaluation 14-days post colonization.

Results

Treatment with (+)-JQ1 suppressed LPS-induced changes in chromatin at distal regulatory elements associated with inflammatory genes, particularly in regions that contain motifs for AP-1 and IRF transcription factors. This resulted in the attenuation of inflammatory gene expression. Treatment with (+)-JQ1 in vivo reduced severity of colitis as compared with vehicle-treated mice.

Conclusion

We identified the mechanism of action associated with a new class of compounds that may mitigate aberrant macrophage responses to bacteria in colitis.

Funding

This work was funded in part through Helmsley Charitable Trust (SHARE Project 2), NIDDK P01DK094779, NIDDK 1R01DK104828, NIDDK P30-DK034987, NIDDK 1R01DK124617, NIH Ruth L. Kirschstein National Research Service Award Individual Predoctoral Fellowship (1F31DK122704), NIH T32 Genetics NIGMS Training Grant (T32-GM007092-43), NIH T32 Translational Medicine Training Grant (T32-GM122741), NIH T32 Gastroenterology Research Training Grant (T32-DK007737), and Crohn’s and Colitis Foundation Student Research Fellowship Award, and Gnotobiotic Animal Facility.
BAI-Net: Individualized Anatomical Cerebral Cartography using Graph Neural Network
Authors: Ma Liang , Zhang Yu , Zhang Hantian , Cheng Luqi , Zhuo Junjie , Shi Weiyang , Lu Yuheng , Li Wen , Yang Zhengyi , Wang Jiaojian , Fan Lingzhong , Jiang Tianzi
Published: July 2021

Brain atlas is an important tool in the diagnosis and treatment of neurological disorders. However, due to large variations in the organizational principles of individual brains, many challenges remain in clinical applications. Brain atlas individualization network (BAI-Net) is an algorithm that subdivides individual cerebral cortex into segregated areas using brain morphology and connectomes. BAI-Net integrates topological priors derived from a group atlas, adjusts the areal probability using the connectivity context derived from diffusion tractography, and provides reliable and explainable individualized brain parcels across multiple sessions and scanners. We demonstrate that BAI-Net outperforms the conventional iterative clustering approach by capturing significantly heritable topographic variations in individualized cartographies. The topographic variability of BAI-Net cartographies shows strong associations with individual variability in brain morphology, connectivity fingerprints and cognitive behaviors. This study provides a new framework for individualized brain cartography and paves the way of atlas-based precision medicine in clinical practice.
The molecular architecture of vimentin filaments
Authors: Eibauer Matthias , Weber Miriam S. , Turgay Yagmur , Sivagurunathan Suganya , Goldman Robert D. , Medalia Ohad
Published: July 2021

Intermediate filaments are integral components of the cytoskeleton in metazoan cells. Due to their specific viscoelastic properties they are principal contributors to flexibility and tear strength of cells and tissues. Vimentin, an intermediate filament protein expressed in fibroblasts and endothelial cells, assembles into ~11 nm thick biopolymers, that are involved in a wide variety of cellular functions in health and disease. Here, we reveal the structure of in-situ polymerized vimentin filaments to a subnanometer resolution by applying cryo-electron tomography to mouse embryonic fibroblasts grown on electron microscopy grids. We show that vimentin filaments are tube-like assemblies with a well-defined helical symmetry. Their structure is comprised of five octameric, spring-like protofibrils harboring 40 vimentin polypeptide chains in cross-section. The protofibrils are connected by the intrinsically disordered head and helix 1A domains of vimentin. Individual filaments display two polymerization states characterized by either the presence or absence of a luminal density along the helical axis. The structure of vimentin filaments unveils the generic building plan of the intermediate filament superfamily in molecular details.
Comprehensive taxon sampling and vetted fossils help clarify the time tree of shorebirds (Aves, Charadriiformes)
Authors: Černý David , Natale Rossy
Published: July 2021

Shorebirds (Charadriiformes) are a globally distributed clade of modern birds and, due to their ecological and morphological disparity, a frequent subject of comparative studies. While molecular phylogenies have been instrumental to resolving the suprafamilial backbone of the charadriiform tree, several higher-level relationships, including the monophyly of plovers (Charadriidae) and the phylogenetic positions of several monotypic families, have remained unclear. The timescale of shorebird evolution also remains uncertain as a result of extensive disagreements among the published divergence dating studies, stemming largely from different choices of fossil calibrations. Here, we present the most comprehensive non-supertree phylogeny of shorebirds to date, based on a total-evidence dataset comprising 336 ingroup taxa (89% of all extant species), 24 loci (15 mitochondrial and 9 nuclear), and 69 morphological characters. Using this phylogeny, we clarify the charadriiform evolutionary timeline by conducting a node-dating analysis based on a subset of 8 loci tested to be clock-like and 16 carefully selected, updated, and vetted fossil calibrations. Our concatenated, species-tree, and total-evidence analyses consistently support plover monophyly and are generally congruent with the topologies of previous studies, suggesting that the higher-level relationships among shorebirds are largely settled. However, several localized conflicts highlight areas of persistent uncertainty within the gulls (Laridae), true auks (Alcinae), and sandpipers (Scolopacidae). At shallower levels, our phylogenies reveal instances of genus-level nonmonophyly that suggest changes to currently accepted taxonomies. Our node-dating analyses consistently support a mid-Paleocene origin for the Charadriiformes and an early diversification for most major subclades. However, age estimates for more recent divergences vary between different relaxed clock models, and we demonstrate that this variation can affect phylogeny-based macroevolutionary studies. Our findings demonstrate the impact of fossil calibration choice on the resulting divergence time estimates, and the sensitivity of diversification rate analyses to the modeling assumptions made in time tree inference.
Exploring the tymovirids landscape through metatranscriptomics data
Authors: Bejerman Nicolás , Debat Humberto
Published: July 2021

Tymovirales is an order of viruses with positive-sense, single-stranded RNA genomes that mostly infect plants, but also fungi and insects. The number of tymovirid sequences has been growing in the last few years with the extensive use of high-throughput sequencing platforms. Here we report the discovery of 31 novel tymovirid genomes associated with 27 different host plant species, which were hidden in public databases. These viral sequences were identified through a homology searches in more than 3,000 plant transcriptomes from the NCBI Sequence Read Archive (SRA) using known tymovirids sequences as query. Identification, assembly and curation of raw SRA reads resulted in 29 viral genome sequences with full-length coding regions, and two partial genomes. Highlights of the obtained sequences include viruses with unique and novel genome organizations among known tymovirids. Phylogenetic analysis showed that six of the novel viruses were related to alphaflexiviruses, seventeen to betaflexiviruses, two to deltaflexiviruses and six to tymoviruses. These findings resulted in the most complete phylogeny of tymovirids to date and shed new light on the phylogenetic relationships and evolutionary landscape of this group of viruses. Furthermore, this study illustrates the complexity and diversity of tymovirids genomes and demonstrates that analyzing SRA public data provides an invaluable tool to accelerate virus discovery and refine virus taxonomy.
The tetrameric assembly of 2-aminomuconic acid dehydrogenase is a functional requirement of cofactor NAD+ binding
Authors: Shi Qiuli , Chen Yanjuan , Li Xinxin , Dong Hui , Chen Cheng , Zhong Zhihui , Yang Cheng , Liu Guangfeng , Su Dan
Published: July 2021

The bacterium Pseudomonas sp. AP–3 is able to use the environmental pollutant 2-aminophenol as its sole source of carbon, nitrogen, and energy. Eight genes (amnA, B, C, D, E, F, G, and H) encoding 2-aminophenol metabolizing enzymes are clustered into a single operon. 2-aminomuconic 6-semialdehyde dehydrogenase (AmnC), a member of the aldehyde dehydrogenase (ALDH) superfamily, is responsible for oxidizing 2-aminomuconic 6-semialdehyde to 2-aminomuconate. In contrast to many other members of the ALDH superfamily, the structural basis of the catalytic activity of AmnC remains elusive. Here, we present the crystal structure of AmnC, which displays a homotetrameric quaternary assembly that is directly involved in its enzymatic activity. The tetrameric state of AmnC in solution was also presented using small-angle X-ray scattering. The tetramerization of AmnC is mediated by the assembly of a protruding hydrophobic beta-strand motif and residues V121 and S123 located in the NAD+-binding domain of each subunit. Dimeric mutants of AmnC dramatically lose NAD+ binding affinity and enzyme activity, indicating that tetrameric assembly of AmnC is required for oxidizing the unstable metabolic intermediate 2-aminomuconic 6-semialdehyde to 2-aminomuconic acid in the 2-aminophenol metabolism pathway.
Quantifying and correcting slide-to-slide variation in multiplexed immunofluorescence images
Authors: Harris C.R. , McKinley E.T. , Roland J.T. , Liu Q. , Shrubsole M.J. , Lau K.S. , Coffey R.J. , Wrobel J. , Vandekar S.N.
Published: July 2021

Motivation

The multiplexed imaging domain is a nascent single-cell analysis field with a complex data structure susceptible to technical variability that disrupts inference. These in situ methods are valuable in understanding cell-cell interactions, but few standardized processing steps or normalization techniques of multiplexed imaging data are available.

Results

We implement and compare data transformations and normalization algorithms in multiplexed imaging data. Our methods adapt the ComBat and functional data registration methods to remove slide effects in this domain, and we present an evaluation framework to compare the proposed approaches. We present clear slide-to-slide variation in the raw, unadjusted data, and show that many of the proposed normalization methods reduce this variation while preserving and improving the biological signal. Further, we find that dividing this data by its slide mean, and the functional data registration methods, perform the best under our proposed evaluation framework. In summary, this approach provides a foundation for better data quality and evaluation criteria in the multiplexed domain.

Availability and Implementation

Source code is provided at https://github.com/statimagcoll/MultiplexedNormalization.

Contact

coleman.r.harris@vanderbilt.edu

Supplementary information

Supplementary information is available online.
The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin
Authors: Krastev Dragomir B. , Li Shudong , Sun Yilun , Wicks Andrew , Weekes Daniel , Badder Luned M. , Knight Eleanor G. , Marlow Rebecca , Calvo Mercedes Pardo , Yu Lu , Talele Tanaji T. , Bartek Jiri , Choudhary Jyoti , Pommier Yves , Pettitt Stephen J. , Tutt Andrew , Ramadan Kristijan , Lord Christopher J.
Published: July 2021

Summary paragraph

Poly-(ADP-ribose) polymerase inhibitors (PARPi) elicit anti-tumour activity in homologous recombination defective cancers by promoting cytotoxic, chromatin-bound, “trapped” PARP1. How cells process trapped PARP1 remains unclear. By exploiting wild-type or trapping-resistant PARP1 transgenes combined with either a rapid immunoprecipitation mass-spectrometry of endogenous proteins (RIME)-based approach, or PARP1 Apex2-proximity labelling linked to mass-spectrometry, we generated proteomic profiles of trapped and non-trapped PARP1 complexes. This combined approach identified an interaction between trapped PARP1 and the ubiquitin-regulated p97 ATPase (aka VCP). Subsequent experiments demonstrated that upon trapping, PARP1 is SUMOylated by the SUMO-ligase PIAS4 and subsequently ubiquitinated by the SUMO-targeted E3-ubiquitin ligase, RNF4, events that promote p97 recruitment and p97 ATPase-mediated removal of trapped-PARP1 from chromatin. Consistent with this, small molecule p97 complex inhibitors, including a metabolite of the clinically-used drug disulfiram (CuET) that acts as a p97 sequestration agent, prolong PARP1 trapping and thus enhance PARPi-induced cytotoxicity in homologous recombination-defective tumour cells and patient-derived tumour organoids. Taken together, these results suggest that p97 ATPase plays a key role in the processing of trapped PARP1 from chromatin and the response of homologous recombination defective tumour cells to PARPi.
Multiple parasitoid species enhance top-down control, but parasitoid performance is context-dependent
Authors: Thierry Mélanie , Pardikes Nicholas A. , Ximénez-Embún Miguel G. , Proudhom Grégoire , Hrček Jan
Published: July 2021

Ecological communities are composed of many species, forming complex networks of interactions. Current environmental changes are altering community composition. We thus need to identify which aspects of species interactions are primarily driven by community structure and which by species identity to predict changes in the functioning of communities. Yet, this partitioning of effects is challenging and thus rarely explored.

Here we disentangled the influence of community structure and the identity of co-occurring species on the outcome of consumer-resource interactions using a host-parasitoid system.

We used four community modules that are common in host-parasitoid communities to represent community structure (i.e., host-parasitoid, exploitative competition, alternative host, and a combination of both exploitative competition and alternative host). We assembled nine different species combinations per community module in a laboratory experiment using a pool of threeDrosophilahosts and three larval parasitoid species. To investigate the potential mechanisms at play, we compared host suppression and parasitoid performance across community modules and species assemblages.

We found that multiple parasitoid species enhanced host suppression due to sampling effect, weaker interspecific than intraspecific competition between parasitoids, and synergism. However, the effects of community structure on parasitoid performance were species-specific and dependent on the identity of co-occurring species. Consequently, multiple parasitoid species generally strengthen top down-control, but the performance of the parasitoids depends on the identity of either the co-occurring parasitoid species, the alternative host species, or both.

Our results highlight the importance of preserving predator diversity for ecosystem functioning, but also show that other effects depend on community composition, and will therefore be likely altered by current environmental changes.
Structural connectivity-based segmentation of the human entorhinal cortex
Authors: Syversen Ingrid Framås , Witter Menno P. , Kobro-Flatmoen Asgeir , Goa Pål Erik , Schröder Tobias Navarro , Doeller Christian F.
Published: July 2021

The medial (MEC) and lateral entorhinal cortex (LEC), widely studied in rodents, are well defined and characterized. In humans, however, the exact locations of their homologues remain uncertain. Previous functional magnetic resonance imaging (fMRI) studies have subdivided the human EC into posterior-medial (pmEC) and anterior-lateral (alEC) parts, but uncertainty remains about the choice of imaging modality and seed regions, in particular in light of a substantial revision of the classical model of EC connectivity based on novel insights from rodent anatomy. Here, we used structural, not functional imaging, namely diffusion tensor imaging (DTI) and probabilistic tractography to segment the human EC based on differential connectivity to other brain regions known to project selectively to MEC or LEC. We defined MEC as more strongly connected to presubiculum and retrosplenial cortex (RSC), and LEC as more strongly connected to distal CA1 and proximal subiculum (dCA1pSub) and orbitofrontal cortex (OFC). Although our DTI segmentation had a larger medial-lateral component than in previous fMRI studies, our results show that the human MEC and LEC homologues have a border oriented both towards the posterior-anterior and medial-lateral axes, supporting the differentiation between pmEC and alEC.
Phylogenetic profiling suggests early origin of the core subunits of Polycomb Repressive Complex 2 (PRC2)
Authors: Sharaf Abdoallah , Vijayanathan Mallika , Oborník Miroslav , Mozgová Iva
Published: July 2021

Polycomb Repressive Complex 2 (PRC2) is involved in establishing transcriptionally silent chromatin states through its ability to methylate lysine 27 of histone H3 by the catalytic subunit Enhancer of zeste [E(z)]. Polycomb group (PcG) proteins play a crucial role in the maintenance of cell identity and in developmental regulation. Previously, the diversity of PRC2 subunits within some eukaryotic lineages has been reported and its presence in early eukaryotic evolution has been hypothesized. So far however, systematic survey of the presence of PRC2 subunits in species of all eukaryotic lineages is missing. Here, we report the diversity of PRC2 core subunit proteins in different eukaryotic supergroups with emphasis on the early-diverged lineages and explore the molecular evolution of PRC2 subunits by phylogenetics. In detail, we investigate the SET-domain protein sequences and their evolution across the four domains of life and particularly focus on the structural diversity of the SET-domain subfamily containing E(z), the catalytic subunit of PRC2. We show that PRC2 subunits are already present in early eukaryotic lineages, strengthening the support for PRC2 emergence prior to diversification of eukaryotes. We identify a common presence of E(z) and ESC, suggesting that Su(z)12 may have emerged later and/or may be dispensable from the evolutionarily conserved functional core of PRC2. Furthermore, our results broaden our understanding of the E(z) evolution within the SET-domain protein family, suggesting possibilities of function evolution. Through this, we shed light on a possible emerging point of the PRC2 and the evolution of its function in eukaryotes.
Collaboration Between Host and Viral Factors Shape SARS-CoV-2 Evolution
Authors: Bamford Connor G. G. , Broadbent Lindsay , Aranday-Cortes Elihu , McCabe Mary , McKenna James , Courtney David , Touzelet Olivier , Ali Ahlam , Roberts Grace , Lopez Campos Guillermo , Simpson David , McCaughey Conall , Fairley Derek , Mills Ken , Power Ultan F. ,   the Breathing Together Investigators
Published: July 2021

SARS-CoV-2 continues to evolve, resulting in several ‘variants of concern’ with novel properties. The factors driving SARS-CoV-2 fitness and evolution in the human respiratory tract remain poorly defined. Here, we provide evidence that both viral and host factors co-operate to shape SARS-CoV-2 genotypic and phenotypic change. Through viral whole-genome sequencing, we explored the evolution of two clinical isolates of SARS-CoV-2 during passage in unmodified Vero-derived cell lines and in parallel, in well-differentiated primary nasal epithelial cell (WD-PNEC) cultures. We identify a consistent, rich genetic diversity arising in vitro, variants of which could rapidly rise to near-fixation with 2 passages. Within isolates, SARS-CoV-2 evolution was dependent on host cells, with Vero-derived cells facilitating more profound genetic changes. However, most mutations were not shared between strains. Furthermore, comparison of both Vero-grown isolates on WD-PNECs disclosed marked growth attenuation mapping to the loss of the polybasic cleavage site (PBCS) in Spike while the strain with mutations in NSP12 (T293I), Spike (P812R) and a truncation of ORF7a remained viable in WD-PNECs. Our work highlights the significant genetic plasticity of SARS-CoV-2 while uncovering an influential role for collaboration between viral and host cell factors in shaping viral evolution and fitness in human respiratory epithelium.
Promotech: A general tool for bacterial promoter recognition
Authors: Chevez-Guardado Ruben , Peña-Castillo Lourdes
Published: July 2021

Promoters are genomic regions where the transcription machinery binds to initiate the transcription of specific genes. Computational tools for identifying bacterial promoters have been around for decades. However, most of these tools were designed to recognize promoters in one or few bacterial species. Here, we present Promotech, a machine-learning-based method for promoter recognition in a wide range of bacterial species. We compared Promotech’s performance with the performance of five other promoter prediction methods. Promotech outperformed these other programs in terms of area under the precision-recall curve (AUPRC) or precision at the same level of recall. Promotech is available at https://github.com/BioinformaticsLabAtMUN/PromoTech.
Generating and testing hypotheses about the fossil record of insect herbivory with a theoretical ecospace
Authors: Schachat Sandra R. , Payne Jonathan L. , Boyce C. Kevin , Labandeira Conrad C.
Published: July 2021

A typical fossil flora examined for insect herbivory contains a few hundred leaves and a dozen or two insect damage types. Paleontologists employ a wide variety of metrics to assess differences in herbivory among assemblages: damage type diversity, intensity (the proportion of leaves, or of leaf surface area, with insect damage), the evenness of diversity, and comparisons of the evenness and diversity of the flora to the evenness and diversity of damage types. Although the number of metrics calculated is quite large, given the amount of data that is usually available, the study of insect herbivory in the fossil record still lacks a quantitative framework that can be used to distinguish among different causes of increased insect herbivory and to generate null hypotheses of the magnitude of changes in insect herbivory over time. Moreover, estimates of damage type diversity, the most common metric, are generated with inconsistent sampling standardization routines. Here we demonstrate that coverage-based rarefaction yields valid, reliable estimates of damage type diversity that are robust to differences among floral assemblages in the number of leaves examined, average leaf surface area, and the inclusion of plant organs other than leaves such as seeds and axes. We outline the potential of a theoretical ecospace that combines various metrics to distinguish between potential causes of increased herbivory. We close with a discussion of the most appropriate uses of a theoretical ecospace for insect herbivory, with the overlapping damage type diversities of Paleozoic gymnosperms and Cenozoic angiosperms as a brief case study.
Formation and characterization of an Al-rich metastable phase in the Al–B phase diagram
Authors: Malkin Alexander I. , Chernyshev Vladimir V. , Ryazantseva Alena A. , Vasiliev Alexander L. , Nickolsky Maximilian S. , Shiryaev Andrei A.
Published: July 2021

Vacuum heat treatment of mechanically alloyed powders of boron and aluminium leads to the formation of a metastable Al-rich phase, which can be quenched. Its structure, composition and thermal stability are established. With the chemical formula Al1.28B the rhombohedral phase is unusually rich in Al. The parameters of the unit cell determined from X-ray powder diffraction are a = 18.3464 (19), c = 8.9241 (9) Å, V = 2601.3 (6) Å3, space group R
3. It is stable on heating to 630°C. It is suggested that this phase is an important intermediate step in the formation of AlB2 and, eventually, of other borides; its nucleation and thermal stability are explained by high elastic energy hindering the formation of equilibrium phases at low temperatures.
Going Flat: Pursuit of a Democratic Organizational Structure
Authors: Abell Julia , Parmar Bidhan L.
Published: July 2021

A 2010 MBA graduate explored her options for full-time employment. She found Ethical Business Company (EBC) and was instantly intrigued. Not only did the company consult on many of the ethical issues that were important to her, but it also had a flat organizational structure. Although it was a riskier choice than going with a larger and more established firm, she was excited about being able to use her skills in direct interaction with clients and senior executives, rather than having them hidden beneath multiple layers of hierarchy. But after three weeks at EBC, she wonders if a flat structure is right for all companies and all employees or if there are certain companies and people who fit better in the hierarchy more than others.
Regional economic growth in India: convergence or divergence?
Authors: Nayak Suryakanta , Sahoo Dukhabandhu
Published: July 2021

Purpose

This paper aims to examine the convergence in per-capita income (measured as per-capita net state domestic product) of regions in India during the period 1990–1991 to 2017–2018. Two separate analyses have also been done for the sub-periods, i.e., 1990–1991 to 2003–2004 and 2004–2005 to 2017–2018, to find out the effect of the second phase of economic liberalization in India.

Design/methodology/approach

In a panel data study, the estimation of absolute and conditional beta (β)-convergence and sigma (σ)-convergence across 17 Indian regions have been done. To measure the dispersion of per-capita income across the regions in India, the standard deviation of logs, Gini coefficient, Mehran measure, Piesch measure, Kakwani measure and Theil index have been estimated. In addition to this, these indices have been regressed over time.

Findings

This study finds the presence of absolute and conditional β-convergence; the regions with low initial per-capita income have grown faster than the regions with high initial per-capita income. Further, this study finds that foreign direct investment (FDI) inflow and the availability of power enhance growth across regions. However, this study finds the presence of σ-divergence, which indicates that the economic inequality among the regions in India has widened over the periods, calling for policy interventions to promote growth in the backward regions through the promotion of FDI inflow and the availability of power.

Originality/value

This study highlights the rising economic inequality among the regions in India by analyzing the latest available data through appropriate econometric techniques.
TymeBank: digital disruption in SA’s banking sector
Authors: Urban Boris , Townsend Stephanie Althea
Published: July 2021

Learning outcomes

Amongst others, these are that students should be able to: identify key components of corporate entrepreneurship; assess the role of technology innovation in terms of creating a competitive advantage; appreciate how an entrepreneurial orientation is related to innovation and growth; and make an informed decision regarding key success factors in influencing growth and sustainability.

Case overview/synopsis

TymeBank became the first fully branchless, digital bank in South Africa when it launched in February 2019. Since then, the bank’s customer base had grown beyond expectation, but the market had also become more competitive, as new digital banks opened for business and traditional banks expanded their range of digital offerings. The case situates the chief executive officer, Tauriq Keeran, in November 2019, considering how whether the bank was doing enough to grow, in the face of this competition.

Complexity academic level

Master’s level business students, as well as entrepreneurship, innovation and digital business at both undergraduate and postgraduate level.

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS 3: Entrepreneurship.
Team culture, employee commitment and job performance in public sectors: a multi-level analysis
Authors: Mishra Santap Sanhari , Kasim Johar Jemal
Published: July 2021

Purpose

The purpose of this paper is to examine the mediating role of employee commitment into the relationship of team culture and job performance at multi-level, in the context of Ethiopian public sectors.

Design/methodology/approach

In the adopted survey design, data were collected from two sources. In the rural development sector of Bale zone in Oromia regional state of Ethiopia, 108 randomly selected employees participated in the survey and also their corresponding 13 team supervisors. By using referent-shift consensus, the individual responses on team culture have been aggregated to team-level scores. In the multi-level modeling, the mediation effect of employee commitment was checked by using Monte Carlo simulation.

Findings

The analysis reveals that employee commitment significantly cross-mediates into the relationship between team culture and job performance. In line with the extended model of team motivation, team culture was found to be significantly cross-related with individual job performance also.

Practical implications

This paper contributes to the knowledge regarding the effects of team culture on employee commitment and job performance. Based on the competing values framework, the authors argue that the cohesion and strong camaraderie among members within a work team establishes a team culture within the organization culture itself.

Originality/value

The novelty of this study lies in the fact that; it is the first study to see the indirect effect of team culture on job performance through employee commitment at multi-level.
Balancing sustainable development and cultural heritage preservation: luxury burial legacies in Singapore
Authors: Ocón David
Published: July 2021

Purpose

The paper aims to provide up-to-date analysis on how a country like Singapore, with a rich tangible and intangible cultural heritage associated with burial customs, approaches heritage preservation while ensuring modernisation and sustainable growth.

Design/methodology/approach

The paper is an exploratory analysis of the association between cultural heritage preservation, particularly the one associated with elaborate burials, and the need for modernisation in Singapore. It mainly uses desk research tools, fieldwork and interviews with death services providers to build a set of conclusions. It employs a historical review approach and uses comparative analyses with other countries in the Asian region to substantiate the arguments.

Findings

The paper provides insights about how, since its independence, Singapore has switched to pragmatic models of growth and development which imply maximising the limited space available, often at the cost of precious cultural heritage. The rapid development has had a significant impact on the country's burial customs and legacies, particularly on elaborate graves and tombs, which traditionally use a considerable amount of space. The analysis concludes that Singapore is in the constant challenge of exploring alternative ways of handling death and its ramifications.

Originality/value

This paper presents a new outlook on the relationship between the preservation of the tangible and intangible cultural heritage associated with death practices and a sustainable approach to modernisation in the context of Singapore.
Serendipity in human information behavior: a systematic review
Authors: Liu Yaxi , Qin Chunxiu , Ma Xubu , Liang Huigang
Published: July 2021

Purpose

Serendipitous information discovery has become a unique and important approach to discovering and obtaining information, which has aroused a growing interest for serendipity in human information behavior. Despite numerous publications, few have systematically provided an overview of current state of serendipity research. Consequently, researchers and practitioners are less able to make effective use of existing achievements, which limits them from making advancements in this domain. Against this backdrop, we performed a systematic literature review to explore the world of serendipity and to recapitulate the current states of different research topics.

Design/methodology/approach

Guided by a prior designed review protocol, this paper conducted both automatic and manual search for available studies published from January 1990 to December 2020 on seven databases. A total of 207 serendipity studies closely related to human information behavior form the literature pool.

Findings

We provide an overview of distinct aspects of serendipity, that is research topics, potential benefits, related concepts, theoretical models, contextual factors and data collection methods. Based on these findings, this review reveals limitations and gaps in the current serendipity research and proposes an agenda for future research directions.

Originality/value

By analyzing current serendipity research, developing a knowledge framework and providing a research agenda, this review is of significance for researchers who want to find new research questions or re-align current work, for beginners who need to quickly understand serendipity, and for practitioners who seek to cultivate serendipity in information environments.
Research on the drivers of undergraduates' intention to use university digital libraries: affinity theory as an additional construct of information system success model
Authors: Xu Fang , Du Jia Tina
Published: July 2021

Purpose

This study aims to examine the factors influencing undergraduates' intention to use university digital libraries by integrating the information system success model and affinity theory.

Design/methodology/approach

Based on the 265 valid responses gathered through a survey, the structural equation modelling (SEM) technique was employed to test the research model and hypotheses.

Findings

The results indicated that system quality and digital libraries (DLs)' affinity significantly affect undergraduates' user satisfaction. However, information quality and service quality does not. User satisfaction has significant impact on undergraduates' intention to use university digital libraries.

Practical implications

Librarians and service providers should focus on enhancing the system quality of digital library and DLs' affinity, to improve the undergraduates' user satisfaction, further motivating undergraduates to use university digital libraries.

Originality/value

The information system success model is enriched by affinity as an additional construct.
Curved-layered material extrusion modeling for thin-walled parts by a 5-axis machine
Authors: Feng Xiaojing , Cui Bin , Liu Yaxiong , Li Lianggang , Shi Xiaojun , Zhang Xiaodong
Published: July 2021

Purpose

The purpose of this paper is to solve the problems of poor mechanical properties, high surface roughness and waste support materials of thin-walled parts fabricated by flat-layered additive manufacturing process.

Design/methodology/approach

This paper proposes a curved-layered material extrusion modeling process with a five-axis motion mechanism. This process has advantages of the platform rotating, non-support printing and three-dimensional printing path. First, the authors present a curved-layered algorithm by offsetting the bottom surface into a series of conformal surfaces and a toolpath generation algorithm based on the geodesic distance field in each conformal surface. Second, they introduce a parallel five-axis printing machine consisting of a printing head fixed on a delta-type manipulator and a rotary platform on a spherical parallel machine.

Findings

Mechanical experiments show the failure force of the five-axis printed samples is 153% higher than that of the three-axis printed samples. Forming experiments show that the surface roughness significantly decreases from 42.09 to 18.31 µm, and in addition, the material consumption reduces by 42.90%. These data indicate the curved-layered algorithm and five-axis motion mechanism in this paper could effectively improve mechanical properties and the surface roughness of thin-walled parts, and realize non-support printing. These methods also have reference value for other additive manufacturing processes.

Originality/value

Previous researchers mostly focus on printing simple shapes such as arch or “T”-like shape. In contrast, this study sets out to explore the algorithm and benefits of modeling thin-walled parts by a five-axis machine. Several validated models would allow comparability in five-axis printing.
Concepts and applications in functional diversity
Authors: Mammola Stefano , Carmona Carlos P. , Guillerme Thomas , Cardoso Pedro
Published: July 2021

The use of functional diversity analyses in ecology has grown exponentially over the past two decades, broadening our understanding of biological diversity and its change across space and time. Virtually all ecological sub‐disciplines recognise the critical value of looking at species and communities from a functional perspective, and this has led to a proliferation of methods for estimating contrasting dimensions of functional diversity.

Differences between these methods and their development generated terminological inconsistencies and confusion about the selection of the most appropriate approach for addressing any particular ecological question, hampering the potential for comparative studies, simulation exercises and meta‐analyses.

Two general mathematical frameworks for estimating functional diversity are prevailing: those based on dissimilarity matrices (e.g. Rao entropy, functional dendrograms) and those relying on multidimensional spaces, constructed as either convex hulls or probabilistic hypervolumes.

We review these frameworks, discuss their strengths and weaknesses and provide an overview of the main R packages performing these calculations. In parallel, we propose a way for organising functional diversity metrics in a unified scheme to quantify the richness, divergence and regularity of species or individuals under each framework. This overview offers a roadmap for confidently approaching functional diversity analyses both theoretically and practically.

A free Plain Language Summary can be found within the Supporting Information of this article.
Bioavailability of iron from novel hydrogen reduced iron powders: Studies in Caco‐2 cells and rat model
Authors: Jyrwa Yvette Wilda , Yaduvanshi Puneeta Singh , Sinha Gourav Ranjan , Dwarapudi Srinivas , Madhari Radhika S , Boiroju Naveen Kumar , Pullakhandam Raghu , Palika Ravindranadh
Published: July 2021

The bioavailability of iron from elemental iron powders, including hydrogen reduced iron powder (HRIP), is influenced by particle size and surface area. In the present study, we investigated the solubility, bioaccessibility, and bioavailability of iron from novel HRIPs (particle size ≤25 and 38 µm generated at low [LT] and high [HT] temperature), with porous morphology and high surface area, in intestinal Caco‐2 cells and in rat models. The acceptability of fortified wheat flour was tested in human volunteers. The iron solubility and ferritin induction in Caco‐2 cells were significantly higher from wheat flour fortified with HRIPs compared to electrolytic iron powder (EIP, ≤45 µm size) either in the absence or presence of ascorbic acid. Nevertheless, ferritin induction in Caco‐2 cells was significantly higher with FeSO4 compared to HRIP or EIP. The relative biological value of HRIPs was significantly higher (≤38HT) or similar compared to EIP in rats. However, serum ferritin was significantly higher in rats fed HRIPs than EIP. Further, wheat flour fortified with HRIP was found to be acceptable for consumption. These findings demonstrate higher iron bioavailability from novel HRIPs compared to the reference EIP (≤45 µm) and merits further studies on toxicity and efficacy.

Practical Application

The use of elemental iron powders for food fortification to alleviate iron deficiency is limited due to its poor bioavailability. The novel hydrogen‐reduced elemental iron powders used in this study had higher bioaccessibility and bioavailability compared to reference EIP (≤45 µm) in in vitro and in vivo models, respectively. Further, there were no sensory differences between roti prepared with fortified or unfortified wheat flour. These results suggest that the novel hydrogen reduced elemental iron powders used in the present study are suitable for wheat flour fortification.