bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence of long-lasting humoral and cellular immunity against SARS-CoV-2 even in elderly COVID-19 convalescents showing a mild to moderate disease progression
Authors: Fischer Bastian , Lindenkamp Christopher , Lichtenberg Christoph , Birschmann Ingvild , Knabbe Cornelius , Hendig Doris
Published: February 2021

After the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in China in late 2019, a pandemic evolved that has claimed millions of lives so far. While about 80 % of infections cause mild or moderate COVID-19 disease, some individuals show a severe progression or even die. Most countries are far from achieving herd-immunity, however, the first approved vaccines offer hope for containment of the virus. Although much is known about the virus, there is a lack of information on the immunity of convalescent individuals.

We here evaluate the humoral and cellular immune response against SARS-CoV-2 in 41 COVID-19 convalescents. As previous studies mostly included younger individuals, one advantage of our study is the comparatively high mean age of the convalescents included in the cohort considered (54 ± 8.4 years). While anti-SARS-CoV-2 antibodies were still detectable in 95 % of convalescents up to 8 months post infection, an antibody-decay over time was generally observed in most donors. Using a multiplex assay, our data additionally reveal that most convalescents exhibit a broad humoral immunity against different viral epitopes. We demonstrate by flow cytometry that convalescent donors show a significantly elevated number of natural killer cells when compared to healthy controls, while no differences were found concerning other leucocyte subpopulations. We detected a specific long-lasting cellular immune response in convalescents by stimulating immune cells with SARS-CoV-2-specific peptides, covering domains of the viral spike, membrane and nucleocapsid protein, and measuring interferon-γ (IFN-γ) release thereafter. We modified a commercially available ELISA assay for IFN-γ determination in whole-blood specimens of COVID-19 convalescents. One advantage of this assay is that it does not require special equipment and can, thus, be performed in any standard laboratory. In conclusion, our study adds knowledge regarding the persistence of immunity of convalescents suffering from mild to moderate COVID-19. Moreover, our study provides a set of simple methods to characterize and confirm experienced COVID-19.
Inequalities in the decline and recovery of pathological cancer diagnoses during the first six months of the COVID-19 pandemic: a population-based study
Authors: Hamilton Ashleigh C. , Donnelly David W. , Loughrey Maurice B. , Turkington Richard C. , Fox Colin , Fitzpatrick Deirdre , O’Neill Ciaran E. , Gavin Anna T. , Coleman Helen G.
Published: February 2021

Background

The restructuring of healthcare systems to cope with the demands of the COVID-19 pandemic has led to a reduction in clinical services such as cancer screening and diagnostics.

Methods

Data from the four Northern Ireland pathology labs was used to assess trends in pathological cancer diagnoses from 1st March to 12th September 2020 overall and by cancer site, gender and age. These trends were compared to the same timeframe from 2017-2019.

Results

Between 1st March and 12th September 2020 there was a 23% reduction in cancer diagnoses compared to the same time period in the preceding three years. Although some recovery occurred in August and September 2020, this revealed inequalities across certain patient groups. Pathological diagnoses of lung, prostate and gynaecological malignancies remained well below pre-pandemic levels. Males and younger/middle-aged adults, particularly the 50-59 year old patient group, also lagged behind other population demographic groups in terms of returning to expected numbers of pathological cancer diagnoses.

Conclusions

There is a critical need to protect cancer diagnostic services in the ongoing pandemic to facilitate timely investigation of potential cancer cases. Targeted public health campaigns may be needed to reduce emerging inequalities in cancer diagnoses as the COVID-19 pandemic continues.
Consequences of the constitutive NOX2 activity in living cells: cytosol acidification, apoptosis, and localized lipid peroxidation
Authors: Valenta Hana , Dupré-Crochet Sophie , Bizouarn Tania , Baciou Laura , Nüsse Oliver , Deniset-Besseau Ariane , Erard Marie
Published: February 2021

The phagocyte NADPH oxidase (NOX2) is a key enzyme of the innate immune system generating superoxide anions (O2•−), precursors of reactive oxygen species. The NOX2 protein complex is composed of six subunits: two membrane proteins (gp91phoxand p22phox) forming the catalytic core, three cytosolic proteins (p67phox, p47phoxand p40phox) and a small GTPase Rac. The sophisticated activation mechanism of the NADPH oxidase relies on the assembly of cytosolic subunits with the membrane-bound components. A chimeric protein, called ‘Trimera’, composed of the essential domains of the cytosolic proteins p47phox(aa 1-286), p67phox(aa 1-212) and full-length Rac1Q61L, enables a constitutive and robust NOX2 activity in cells without the need of any stimulus. We employed Trimera as a single activating protein of the phagocyte NADPH oxidase in living cells and examined the consequences on the cell physiology of this continuous and long-term NOX activity. We showed that the sustained high level of NOX activity causes acidification of the intracellular pH, triggers apoptosis and leads to local peroxidation of lipids in the membrane. These local damages to the membrane correlate with the strong tendency of the Trimera to clusterize in the plasma membrane observed by FRET-FLIM microscopy.

Highlights

Trimera is a tool to trigger a continuous ROS production in living cells

Continuous NOX2 activity causes cytosol acidification and apoptosis

ROS overproduction leads to localized oxidation of the membrane lipids

Trimera tends to clusterize in the plasma membrane of COSNOX and COS-7 cells
Developmental depression-facilitation shift controls excitation-inhibition balance
Authors: Jia David W. , Costa Rui Ponte , Vogels Tim P.
Published: February 2021

Changes in the short-term dynamics of excitatory synapses over development have been observed throughout cortex, but their purpose and consequences remain unclear. Here, we propose that developmental changes in synaptic dynamics buffer the effect of slow inhibitory long-term plasticity, allowing for continuously stable neural activity. Using computational modelling we demonstrate that early in development excitatory short-term depression quickly stabilises neural activity, even in the face of strong, unbalanced excitation. We introduce a model of the commonly observed developmental shift from depression to facilitation and show that neural activity remains stable throughout development, while inhibitory synaptic plasticity slowly balances excitation, consistent with experimental observations. Our model predicts changes in the input responses from phasic to phasic-and-tonic and more precise spike timings. We also observe a gradual emergence of synaptic working memory mediated by short-term facilitation. We conclude that the developmental depression-to-facilitation shift may control excitation-inhibition balance throughout development with important functional consequences.
Dense Functional and Molecular Readout of a Circuit Hub in Sensory Cortex
Authors: Condylis Cameron , Ghanbari Abed , Manjrekar Nikita , Bistrong Karina , Yao Shenqin , Yao Zizhen , Nguyen Thuc Nghi , Zeng Hongkui , Tasic Bosiljka , Chen Jerry L.
Published: February 2021

Information processing in the neocortex is carried out by neuronal circuits composed of different cell types. Recent census of the neocortex using single cell transcriptomic profiling has uncovered more than 100 putative cell types which subdivide major classes of excitatory and inhibitory neurons into distinct subclasses. The extent to which this molecular classification predicts distinct functional roles during behavior is unclear. Here, we combined population recordings using two-photon calcium imaging with spatial transcriptomics using multiplexed fluorescentin situhybridization to achieve dense functional and molecular readout of cortical circuits during behavior. We characterized task-related responses across major transcriptomic neuronal subclasses and types in layer 2/3 of primary somatosensory cortex as mice performed a tactile working memory task. We find that as neurons are segregated into increasingly discrete molecular types, their task-related properties continue to differentiate. We identify an excitatory cell type, Baz1a, that is highly driven by tactile stimuli. Baz1a neurons homeostatically maintain stimulus responsiveness during altered sensory experience and show persistent enrichment of subsets of immediately early genes includingFos. Measurements of functional and anatomical connectivity reveal that upper layer 2/3 Baz1a neurons preferentially innervate somatostatin-expressing inhibitory neurons. We propose that this connection motif reflects a sensory-driven circuit hub that orchestrates local sensory processing in superficial layers of the neocortex.
A mitochondrial genome phylogeny of voles and lemmings (Rodentia: Arvicolinae): evolutionary and taxonomic implications
Authors: Abramson Natalia I. , Bodrov Semyon Yu. , Bondareva Olga V. , Genelt-Yanovskiy Evgeny A. , Petrova Tatyana V.
Published: February 2021

Arvicolinae is one of the most impressive placental radiations with over 150 extant and numerous extinct species that emerged since the Miocene in the Northern Hemisphere. The phylogeny of Arvicolinae has been studied intensively for several decades using morphological and genetic methods. Here, we sequenced 30 new mitochondrial genomes to better understand the evolutionary relationships among the major tribes and genera within the subfamily. The phylogenetic and molecular dating analyses based on 11,391 bp concatenated alignment of protein-coding mitochondrial genes confirmed the monophyly of the subfamily. While Bayesian analysis provided a high resolution across the entire tree, Maximum Likelihood tree reconstruction showed weak support for the ordering of divergence and interrelationships of tribal level taxa within the most ancient radiation. Both the interrelationships among tribes Lagurini, Ellobiusini and Arvicolini, comprising the largest radiation and the position of the genusDinaromyswithin it also remained unresolved. For the first time complex relationships between genus level taxa within the species-rich tribe Arvicolini received full resolution. ParticularlyLemmiscuswas robustly placed as sister to the snow volesChionomysin the tribe Arvicolini in contrast with a long-held belief of its affinity with Lagurini. Molecular dating of the origin of Arvicolinae and early divergences obtained from the mitogenome data were consistent with fossil records. The mtDNA estimates for putative ancestors of the most genera within Arvicolini appeared to be much older than it was previously proposed in paleontological studies.
Validation of the Early Warning and Response System (EWARS) for dengue outbreaks: Evidence from the national vector control program in Mexico
Authors: Benitez-Valladares David , Kroeger Axel , Sánchez Tejeda Gustavo , Hussain-Alkhateeb Laith
Published: February 2021

Background

During 2017, twenty health districts (locations) in Mexico implemented a dengue outbreak early warning and response system (EWARS) that uses epidemiological, meteorological and entomological variables (alarm indicators) to predict dengue outbreaks and triggers early response activities.

Eleven of these districts were analyzed as they presented reliable information. Nine districts presented outbreak alarms but without subsequent outbreaks (“non-outbreak districts”) and two presented after the alarms dengue outbreaks (“outbreak districts”). This study is concerned with i) if the alarms without outbreaks were false alarms or if the control services had established effective response activities averting an outbreak and ii) if vector control activities can mitigate or even avert dengue outbreaks.

Methods

Five components of dengue outbreak response (larval control, entomological studies with water container interventions, focal spraying, indoor residual spraying, space spraying) were quantitatively analyzed across two groups (”outbreak districts” and “non-outbreak districts”).

Results

The average coverage of vector control and responses were higher in non-outbreak districts and across all five components. In the “outbreak districts” the response activities started late and were of much lower intensity compared to “non-outbreak districts”. District vector control teams demonstrated diverse compliance with local guidlines for ‘initial’, ‘early’ and ‘late’ responses to outbreak alarms which could explain the different outcomes observed following the outbreak alarms.

Conclusion

findings from this study plausibly demonstrates important operational scenarios when succeeding or failing alarms signals generated by EWARS at national level. This study presents evidence warranting for further investigation into the effectiveness and cost-effectiveness of EWARS using gold-standard designs.
CD4 T cell help prevents CD8 T cell exhaustion and promotes control ofMycobacterium tuberculosisinfection
Authors: Lu Yu-Jung , Barreira-Silva Palmira , Boyce Shayla , Powers Jennifer , Cavallo Kelly , Behar Samuel M.
Published: February 2021

CD4 T cells are essential for immunity to tuberculosis because they produce cytokines including interferon-γ. Whether CD4 T cells act as “helper” cells to promote optimal CD8 T cell responses duringMycobacterium tuberculosisis unknown. Using two independent models, we show that CD4 T cell help enhances CD8 effector functions and prevents CD8 T cell exhaustion. We demonstrate synergy between CD4 and CD8 T cells in promoting the survival of infected mice. Purified helped, but not helpless, CD8 T cells efficiently restrict intracellular bacterial growthin vitro. Thus, CD4 T cell help plays an essential role in generating protective CD8 T cell responses againstM. tuberculosisinfectionin vitroandin vivo. We infer vaccines that elicit both CD4 and CD8 T cells are more likely to be successful than vaccines that elicit only CD4 or CD8 T cells.
Genetic incompatibilities do not snowball in a demographic model of speciation
Authors: Maya-Lastra Carlos A. , Eaton Deren A. R.
Published: February 2021

Two populations evolving in isolation can accumulate genetic differences over time that cause incompatibilities in their hybrid offspring. These “Dobzhansky-Muller incompatibilities” (DMIs) are predicted to accumulate at a rate faster than linear as the number of incompatible gene interactions “snowballs”. Here we show that this snowball prediction is an artifact of two unrealistic modeling assumptions that stem from ignoring demography. We introduce a new alternative “demographic speciation model” in which the rate of DMI accumulation between populations is affected by the efficiency of purifying selection to remove incompatibilities that arise within populations. This model yields new testable predictions for understanding the tempo and mode of speciation based on population demographic parameters. A large-scale empirical analysis of bird and mammal datasets supports a unique prediction of our model: a negative relationship between effective population sizes and speciation rates. Our results challenge views of the snowball theory, and of ecological speciation models rooted in positive selection, showing instead that purifying selection may play a major role in mediating speciation rates.
Oral Hsp90 inhibitor, SNX-5422, attenuates SARS-CoV-2 replication and dampens inflammation in airway cells
Authors: Goswami Ria , Russell Veronica S. , Tu Joshua J. , Hughes Philip , Kelly Francine , Langel Stephanie N. , Steppe Justin , Palmer Scott M. , Haystead Timothy , Blasi Maria , Permar Sallie R.
Published: February 2021

Currently available SARS-CoV-2 therapeutics are targeted towards moderately to severely ill patients and require intravenous infusions, with limited options for exposed or infected patients with no or mild symptoms. While vaccines have demonstrated protective efficacy, vaccine hesitancy and logistical distribution challenges will delay their ability to end the pandemic. Hence, there is a need for rapidly translatable, easy-to-administer-therapeutics, that can prevent SARS-CoV-2 disease progression, when administered in the early stages of infection. We demonstrate that an orally bioavailable Hsp90 inhibitor, SNX-5422, currently in clinical trials as an anti-cancer therapeutic, inhibits SARS-CoV-2 replicationin vitroat a high selectivity index. SNX-5422 treatment of human primary airway epithelial cells dampened expression of inflammatory pathways associated with poor SARS-CoV-2 disease outcomes. Additionally, SNX-5422 interrupted expression of host factors that are crucial for SARS-CoV-2 replication machinery. Development of SNX-5422 as SARS-CoV-2-early-therapy will dampen disease severity, resulting in better clinical outcomes and reduced hospitalizations.
The Mesodiencephalic Junction as a Central Hub for Cerebro-Cerebellar Communication
Authors: Wang Xiaolu , Novello Manuele , Gao Zhenyu , Ruigrok Tom J.H. , De Zeeuw Chris I.
Published: February 2021

Most studies investigating the impact of cerebral cortex (CC) onto the cerebellum highlight the role of the pontine mossy fibre system. However, cerebro-cerebellar communication may also be mediated by the olivary climbing fibres via a hub in the mesodiencephalic junction (MDJ). Here, we show that rostromedial and caudal parts of mouse CC predominantly project to the principal olive via the rostroventral MDJ and that more rostrolateral CC regions prominently project to the rostral medial accessory olive via the caudodorsal MDJ. Moreover, transneuronal tracing results show that the cerebellar nuclei innervate the olivary-projecting neurons in the MDJ that receive input from CC, and that they adhere to the same topographical relations. By unravelling these topographic and dense, mono- and disynaptic projections from the CC through the MDJ and inferior olive to the cerebellum, this work establishes that cerebro-cerebellar communication can be mediated by both the mossy fibre and climbing fibre system.
Deep Brain Stimulation for Parkinson’s Disease Induces Spontaneous Cortical Hypersynchrony In Extended Motor and Cognitive Networks
Authors: Wang Maxwell B , Boring Matthew J , Ward Michael J , Richardson R Mark , Ghuman Avniel Singh
Published: February 2021

The mechanism of action of deep brain stimulation (DBS) for Parkinson’s disease remains unclear. Studies have shown that DBS decreases pathological beta hypersynchrony between the basal ganglia and motor cortex. However, little is known about DBS’s effects on long range corticocortical synchronization. Here, we use machine learning combined with spectral graph theory to compare resting-state cortical connectivity between the off and on-stimulation states and compare these differences to healthy controls. We found that turning DBS on increased high beta and gamma band coherence in a cortical circuit spanning the motor, occipitoparietal, middle temporal, and prefrontal cortices. We found no significant difference between DBS-off and controls in this network with multivariate pattern classification showing that the brain connectivity pattern in control subjects is more like those during DBS-off than DBS-on. These results show that therapeutic DBS increases spontaneous high beta-gamma synchrony in a network that couples motor areas to broader cognitive systems.
Blood progenitor redox homeostasis through GABA control of TCA cycle inDrosophilahematopoiesis
Authors: Goyal Manisha , Tomar Ajay , Madhwal Sukanya , Mukherjee Tina
Published: February 2021

The importance of reactive oxygen species (ROS) in myeloid cell development and function is well-established. However, a comprehensive understanding of metabolic states controlling ROS levels during hematopoiesis remains elusive. Myeloid-like blood progenitor cells of theDrosophilalarvae reside in a specialized hematopoietic organ called the lymph gland. We find that these progenitors in homeostasis, utilize TCA to generate ROS. Excessive activation of TCA however raises ROS levels causing them to precociously differentiate and leads to retardation of lymph gland size. Thus, to maintain ROS homeostasis, progenitor cells utilize systemically derived GABA. GABA internalization and catabolism via inhibiting hydroxy prolyl hydroxylase (Hph) activity, promotes pyruvate dehydrogenase kinase enzyme activity (PDK). PDK controls inhibitory phosphorylation of pyruvate dehydrogenase (PDH), the rate-limiting enzyme, connecting pyruvate to TCA cycle and OXPHOS. Thus, by regulating PDK, GABA regulates progenitor TCA activity and ROS levels. In addition to this, GABA-catabolism/Hph axis via Hifα/Sima drives a glycolytic state in progenitor cells. The dual control established by GABA on PDK and Sima maintains progenitor cell metabolism and sustains ROS homeostasis necessary for their development. Taken together, our study demonstrates the metabolic underpinnings of GABA in myeloid ROS regulation and their development, the relevance of which may be broadly conserved.
Marine heatwaves depress metabolic activity and impair cellular acid-base homeostasis in reef-building corals regardless of bleaching susceptibility
Authors: Innis Teegan , Allen-Waller Luella , Brown Kristen Taylor , Sparagon Wesley , Carlson Christopher , Kruse Elisa , Huffmyer Ariana S. , Nelson Craig E. , Putnam Hollie M. , Barott Katie L.
Published: February 2021

Ocean warming is causing global coral bleaching events to increase in frequency, resulting in widespread coral mortality and disrupting the function of coral reef ecosystems. However, even during mass bleaching events, many corals resist bleaching despite exposure to abnormally high temperatures. While the physiological effects of bleaching have been well documented, the consequences of heat stress for bleaching resistant individuals are not well understood. In addition, much remains to be learned about how heat stress affects cellular level processes that may be overlooked at the organismal level, yet are crucial for coral performance in the short term and ecological success over the long term. Here we compared the physiological and cellular responses of bleaching resistant and bleaching susceptible corals throughout the 2019 marine heatwave in Hawai‘i, a repeat bleaching event that occurred four years after the previous regional event. Relative bleaching susceptibility within species was consistent between the two bleaching events, yet corals of both resistant and susceptible phenotypes exhibited pronounced metabolic depression during the heatwave. At the cellular level, bleaching susceptible corals had lower intracellular pH than bleaching resistant corals at the peak of bleaching for both symbiont-hosting and symbiont-free cells, indicating greater disruption of acid-base homeostasis in bleaching susceptible individuals. Notably, cells from both phenotypes were unable to compensate for experimentally induced cellular acidosis, indicating that acid-base regulation was significantly impaired at the cellular level even in bleaching resistant corals and in cells containing symbionts. Thermal disturbances may thus have substantial ecological consequences, as even small reallocations in energy budgets to maintain homeostasis during stress can negatively affect fitness. These results suggest concern is warranted for corals coping with ocean acidification alongside ocean warming, as the feedback between temperature stress and acid-base regulation may further exacerbate the physiological effects of climate change.
Cell Communication Network factor 4 promotes tumor-induced immunosuppression in melanoma
Authors: Fernandez Audry , Deng Wentao , McLaughlin Sarah L. , Pirkey Anika C. , Rellick Stephanie L. , Klinke David J.
Published: February 2021

Immune cell composition within the tumor microenvironment is regulated by tumor-derived factors. Cell Communication Network factor 4 (CCN4/WISP1) is a matricellular protein secreted by cancer cells that promotes metastasis by inducing the epithelial-mesenchymal transition. While metastatic dissemination limits patient survival, the absence of anti-tumor immunity also associates with poor patient out-comes with recent work suggesting these two clinical correlates are linked. Motivated by finding that CCN4 was associated with a dampened anti-tumor immune contexture in patients diagnosed with primary melanoma, we tested for a direct causal link by knocking out CCN4 (CCN4-KO) in the B16F0 and YUMM1.7 mouse models for melanoma. Tumor growth was significantly reduced when CCN4-KO melanoma cells were implanted subcutaneously in immunocompetent C57BL/6 mice but not in immunodeficient NSG mice. Correspondingly, the frequency of total CD45+tumor-infiltrating leukocytes was significantly increased in CCN4-KO tumors, with increased natural killer (NK) and effector CD8+T cells and reduced myeloid-derived suppressor cells (MDSC). Additionally, the absence of tumor-derived CCN4 was associated with an impaired splenic generation of suppressive granulocytic MDSC. Among mechanisms linked to local immunosuppression, we found CCN4 directly suppressed antigen-induced IFNγrelease by CD8+T cells, promoted glycolysis and consequent lactate release by melanoma cells, and enhanced tumor secretion of MDSC-attracting chemokines like CCL2 and CXCL1. Finally, CCN4-KO in B16F0 and YUMM1.7 melanoma cells complemented the anti-tumor effect of immune checkpoint blockade (ICB) therapy. Overall, our results suggest that CCN4 promotes tumor-induced immunosuppression and is a potential target for therapeutic combinations with ICB.

Statement of Significance

Given emerging interest in understanding the interplay between functional plasticity and anti-tumor immunity, Cell Communication Network factor 4, a secreted matricellular protein linked to promoting metastasis in melanoma, also suppresses anti-tumor immunity.
CellWalkR: An R Package for integrating single-cell and bulk data to resolve regulatory elements
Authors: Przytycki Pawel F. , Pollard Katherine S.
Published: February 2021

While single-cell open chromatin (scATAC-seq) data allows for the identification of cell type-specific regulatory regions, it is much sparser than bulk data. CellWalkR is an R package that performs an integration of external labeling and bulk epigenetic data with scATAC-seq using a network-based random walk model to help overcome this sparsity. Outputs include cell type labels for individual cells and regulatory regions.

Availability and implementation

CellWalkR is freely available as an R package under a GNU GPL-2.0 License, and can be accessed fromhttps://github.com/PFPrzytycki/CellWalkRwith an accompanying vignette for analyzing example data.
Distrust Before First Sight? Examining Knowledge- and Appearance-Based Effects of Trustworthiness on the Visual Consciousness of Faces
Authors: Eiserbeck Anna , Enge Alexander , Rabovsky Milena , Rahman Rasha Abdel
Published: February 2021

The present EEG study with 32 healthy participants investigated whether affective knowledge about a person influences the visual awareness of their face, additionally considering the impact of facial appearance. Faces differing in perceived trustworthiness based on appearance were associated with negative or neutral social information and shown as target stimuli in an attentional blink task. As expected, participants showed enhanced awareness of faces associated with negative compared to neutral social information. On the neurophysiological level, this effect was connected to differences in the time range of the early posterior negativity (EPN)—a component associated with enhanced attention and facilitated processing of emotional stimuli. The findings indicate that the social-affective relevance of a face based on emotional knowledge is accessed during a phase of attentional enhancement for conscious perception and can affect prioritization for awareness. In contrast, no clear evidence for influences of facial trustworthiness during the attentional blink was found.
A general role for MIA3/TANGO1 in secretory pathway organization and function
Authors: McCaughey Janine , Stevenson Nicola L. , Mantell Judith M. , Neal Chris R. , Paterson Alex , Heesom Kate , Stephens David J.
Published: February 2021

Complex machinery is required to drive secretory cargo export from the endoplasmic reticulum, an essential process in eukaryotic cells. In vertebrates, the Mia3 gene encodes two major forms of Transport ANd Golgi Organization Protein 1 (TANGO1S and TANGO1L). Here, using genome engineering of human cells, light microscopy, secretion assays, genomics, and proteomics we show that disruption of the longer form, TANGO1L, results in relatively minor defects in secretory pathway organization and function including limited impacts on procollagen secretion. In contrast, loss of both long and short forms results in major defects in cell organization and secretion. These include a failure to maintain the localization of ERGIC53 and SURF4 to the ER-Golgi Intermediate Compartment and dramatic changes to the ultrastructure of the ER-Golgi interface. Disruption of TANGO1 expression also causes significant changes in early secretory pathway gene and protein expression. Disruption of both TANGO1L and TANGO1S expression impairs secretion not only of large proteins, including procollagens, but of all types of secretory cargo including small soluble proteins. Our data support a general role for Mia3/TANGO1 in maintaining both secretory pathway structure and function in vertebrate cells.
Linear-time cluster ensembles of large-scale single-cell RNA-seq and multimodal data
Authors: Do Van Hoan , Rojas Ringeling Francisca , Canzar Stefan
Published: February 2021

A fundamental task in single-cell RNA-seq (scRNA-seq) analysis is the identification of transcriptionally distinct groups of cells. Numerous methods have been proposed for this problem, with a recent focus on methods for the cluster analysis of ultralarge scRNA-seq data sets produced by droplet-based sequencing technologies. Most existing methods rely on a sampling step to bridge the gap between algorithm scalability and volume of the data. Ignoring large parts of the data, however, often yields inaccurate groupings of cells and risks overlooking rare cell types. We propose method Specter that adopts and extends recent algorithmic advances in (fast) spectral clustering. In contrast to methods that cluster a (random) subsample of the data, we adopt the idea of landmarks that are used to create a sparse representation of the full data from which a spectral embedding can then be computed in linear time. We exploit Specter's speed in a cluster ensemble scheme that achieves a substantial improvement in accuracy over existing methods and identifies rare cell types with high sensitivity. Its linear-time complexity allows Specter to scale to millions of cells and leads to fast computation times in practice. Furthermore, on CITE-seq data that simultaneously measures gene and protein marker expression, we show that Specter is able to use multimodal omics measurements to resolve subtle transcriptomic differences between subpopulations of cells.
Iterative epigenomic analyses in the same single cell
Authors: Ohnuki Hidetaka , Venzon David J. , Lobanov Alexei , Tosato Giovanna
Published: February 2021

Gene expression in individual cells is epigenetically regulated by DNA modifications, histone modifications, transcription factors, and other DNA-binding proteins. It has been shown that multiple histone modifications can predict gene expression and reflect future responses of bulk cells to extracellular cues. However, the predictive ability of epigenomic analysis is still limited for mechanistic research at a single cell level. To overcome this limitation, it would be useful to acquire reliable signals from multiple epigenetic marks in the same single cell. Here, we propose a new approach and a new method for analysis of several components of the epigenome in the same single cell. The new method allows reanalysis of the same single cell. We found that reanalysis of the same single cell is feasible, provides confirmation of the epigenetic signals, and allows application of statistical analysis to identify reproduced reads using data sets generated only from the single cell. Reanalysis of the same single cell is also useful to acquire multiple epigenetic marks from the same single cells. The method can acquire at least five epigenetic marks: H3K27ac, H3K27me3, mediator complex subunit 1, a DNA modification, and a DNA-interacting protein. We can predict active signaling pathways in K562 single cells using the epigenetic data and confirm that the predicted results strongly correlate with actual active signaling pathways identified by RNA-seq results. These results suggest that the new method provides mechanistic insights for cellular phenotypes through multilayered epigenome analysis in the same single cells.
Application of UAVs for tourism security and safety
Authors: Ko Young Dae , Song Byung Duk
Published: February 2021

Purpose

In the tourism industry, unmanned aerial vehicles (UAVs) can perform monitoring and patrol missions to protect assets and tourists at attractions such as coastal areas, canyons, national parks, etc. Such use of UAVs can improve safety and security of tourism attraction and facilitate tourism industry. However, there is a key issue regarding economic investment and efficient operation for actual system implementation. The purpose of this paper is to provide a guideline for supporting economic investment and the efficient operation of UAV system in the tourism industry.

Design/methodology/approach

Ideas and methodologies have been proposed to overcome the fundamental limitations of commercial UAVs. A mathematical optimization model is developed to determine the optimal number of UAVs to be purchased, and its operation schedules simultaneously.

Findings

Using proposed concept and methodology, UAVs can support long duration of missions. Economic system design as well as the operation schedule is derived with the hypothesis data in Kkot-Ji beach in Korea. The proposed methodology and approach is expected to have huge potential at many tourism attractions to achieve the safety and security of tourists.

Practical implications

The result of this study can facilitate practical use of UAVs in the tourism industry. Furthermore, it is applicable in many industries that need UAV systems such as national defence, agriculture, disaster management, etc.

Originality/value

The proposed study suggests a solution to handle fundamental weakness of UAVs and support long duration of missions. In addition, this study incorporates economic system design issue and operation issue simultaneously.
Impulsive purchasing and luxury brand loyalty in WeChat Mini Program
Authors: Rao Qianhui , Ko Eunju
Published: February 2021

Purpose

This study aims to explore the impact of the use of the WeChat Mini Program by luxury brands on consumers' fashion impulsive purchasing and brand loyalty.

Design/methodology/approach

The stimulus–organism–response (S–O–R) model is adapted to construct a model (i.e. stimulus: patron status, informativeness and entertainment; organism: perceived enjoyment and perceived usefulness; responses: impulse buying behavior and luxury brand loyalty). An online survey was conducted by 200 Chinese participants who experienced WeChat Mini Program and luxury brand purchase.

Findings

The results indicate that luxury consumption related factors, task-related factors and mood-related factors in WeChat Mini Program have positive effects on consumers' impulsive purchasing behavior through perceived enjoyment and perceived usefulness.

Research limitations/implications

This study provides a new understanding about factors influencing consumers' behaviors and brand loyalty in WeChat Mini Program.

Originality/value

The mobile social platform has been considered as an advanced tool for advertising. As the most popular mobile social media used by over 1 bn monthly active Chinese users—WeChat, little research attention has been attracted by researchers. To stress the WeChat Mini Program's role in the S-commerce background can fill the gap between the literature of the utilization of new marketing tools in retailing, marketing and the whole fashion industry. In terms of marketing management, the paper conducted research that participated by new generation consumers and offers some practical managerial implications for brands, retailers and marketers to generate new business models and marketing strategies.
Higher education in business: a model for international students' choice
Authors: Hung Nguyen Tan
Published: February 2021

Purpose

With a considerable increase in international students studying in Asia, Taiwan has become one of the most popular study destinations. The purpose of this study is to investigate the factors and processes leading to the choice of international students studying in Taiwan. In addition, an appropriate model of students' choice that explored the impact of the motivation, career planning and the decision-making process on student's choice was constructed.

Design/methodology/approach

This study was conducted using the mixed-methods methodology. A qualitative approach was used for in-depth interviews with 15 international students studying in Taiwan. The data collected from the interviews were used to create questionnaires to survey over 500 participants. The responses were subsequently used for quantitative analysis.

Findings

The results revealed the main factors of the motivation of international students to study abroad in Taiwan. A model of how the students' choice process operated was also provided. The quantitative findings indicated that students' motivation and career planning were significantly correlated, whereas both factors directly affected the decision-making process. On another note, the students' decision-making process remained a mediator between motivation, career planning and students' choice.

Originality/value

This research contributed to methodology development and the practicality of HE management. In addition, a comprehensive model was developed that diagrammatically demonstrated international students' choice in Taiwan.
Analysis of circuit performance of Ge-Si hetero structure TFET based on analytical model
Authors: Ghosh Sudipta , Venkateswaran P. , Sarkar Subir Kumar
Published: February 2021

Purpose

High packaging density in the present VLSI era builds an acute power crisis, which limits the use of MOSFET device as a constituent block in CMOS technology. This leads researchers in looking for alternative devices, which can replace the MOSFET in CMOS VLSI logic design. In a quest for alternative devices, tunnel field effect transistor emerged as a potential alternative in recent times. The purpose of this study is to enhance the performances of the proposed device structure and make it compatible with circuit implementation. Finally, the performances of that circuit are compared with CMOS circuit and a comparative study is made to find the superiority of the proposed circuit with respect to conventional CMOS circuit.

Design/methodology/approach

Silicon–germanium heterostructure is currently one of the most promising architectures for semiconductor devices such as tunnel field effect transistor. Analytical modeling is computed and programmed with MATLAB software. Two-dimensional device simulation is performed by using Silvaco TCAD (ATLAS). The modeled results are validated through the ATLAS simulation data. Therefore, an inverter circuit is implemented with the proposed device. The circuit is simulated with the Tanner EDA tool to evaluate its performances.

Findings

The proposed optimized device geometry delivers exceptionally low OFF current (order of 10^−18 A/um), fairly high ON current (5x10^−5 A/um) and a steep subthreshold slope (20 mV/decade) followed by excellent ON–OFF current ratio (order of 10^13) compared to the similar kind of heterostructures. With a very low threshold voltage, even lesser than 0.1 V, the proposed device emerged as a good replacement of MOSFET in CMOS-like digital circuits. Hence, the device is implemented to construct a resistive inverter to study the circuit performances. The resistive inverter circuit is compared with a resistive CMOS inverter circuit. Both the circuit performances are analyzed and compared in terms of power dissipation, propagation delay and power-delay product. The outcomes of the experiments prove that the performance matrices of heterojunction Tunnel FET (HTFET)-based inverter are way ahead of that of CMOS-based inverter.

Originality/value

Germanium–silicon HTFET with stack gate oxide is analytically modeled and optimized in terms of performance matrices. The device performances are appreciable in comparison with the device structures published in contemporary literature. CMOS-like resistive inverter circuit, implemented with this proposed device, performs well and outruns the circuit performances of the conventional CMOS circuit at 45-nm technological node.
Effect of production speed on polyester/nylon intermingled yarn and melange fabric properties
Authors: G.L.D. Wickramasinghe G.L.D. Wickramasinghe , Dolawatte Sameera Umesh , Thebuwana Isuru Udayanga , Botheju W.W.S. Sampath
Published: February 2021

Purpose

The main objectives of this research work were to investigate the effect of production speed on intermingled yarn properties and melange fabric properties with special reference to melange appearance.

Design/methodology/approach

Polyester/nylon intermingled yarns were produced using an SSM DP3-C air-intermingling machine using commercial process parameters and Heberlein P212 nozzle. Melange fabric samples were knitted from polyester/nylon intermingled yarns while maintaining the same parameters to avoid knitting variations. The fabric samples were dyed using a sample dyeing machine while maintaining dye recipe and dyeing parameters constant to avoid dyeing variations.

Findings

The production speed has significant effect on intermingled yarn and melange fabric properties. When the production speed is increased, mingle points, mingle stability, linear density, strength and the elongation of the intermingled yarns decreases. When the production speed is increased, fabric weight decreases and the melange effect varies from dot-like appearance to line-like appearance.

Research limitations/implications

Only the effect of production speed on intermingled yarn and melange fabric properties is discussed in this paper. Appearance evaluating systems developed in this research are limited to melange fabrics produced using air-intermingled yarns with two colour components.

Practical implications

Results indicate that the intermingled yarns for the application of melange fabrics should be developed with optimum intermingling speeds, and it should not be changed during the production since production speed has significant effect on yarn and fabric parameters. Therefore, melange appearance and fabric weight may vary between fabric lots with different production speeds even though all the other parameters are kept constant. Further, melange appearance evaluation method developed in this research could be used as a guide in developing melange fabrics.

Originality/value

This research introduced a qualitative and a quantitative method to analyse melange fabric appearance. This melange appearance evaluation method can be used as a guide to achieve specific melange effect in the sample development stage. Further, when a melange sample appearance catalogue is developed for all the variables for a particular fabric type using this evaluation method, customer requested appearance can be achieved in minimum sample trials which save time, capacity, money and customer credibility.
Understanding peer recommendation in mobile social games: the role of needs–supplies fit and game identification
Authors: Wang Le
Published: February 2021

Purpose

The purpose of this paper is to understand the antecedents of peer recommendations (generating positive word-of-mouth and recruiting others) in the context of mobile social games.

Design/methodology/approach

Drawing on the needs–supplies fit framework and social identity theory, this paper proposes that game design characteristics (challenge, fairness, innovativeness and ease of use) influence game identification, which further predicts word-of-mouth (WOM) generation and recruitment intention. This paper further suggests fits between gamer orientation (passing time and seeking achievements) and game design lead to enhanced game identification. The model was tested using data from an empirical survey with 767 mobile social gamers.

Findings

Game challenge, game fairness, game innovativeness and ease of use are positively associated with game identification, whereas game identification positively predicts WOM generation and recruitment intention. Achievement-seeking use was found to enhance the effects of game challenge and game fairness on game identification, and passing time use was found to strengthen the effects of game innovativeness and ease of use on game identification.

Research limitations/implications

The findings of this study provide operable implications to facilitate peer recommendations in a mobile gaming context. The model was only tested within the context of mobile social games, however, so caution is advised when generalizing the findings to other game subgenres.

Originality/value

This study distinguishes itself from other peer recommendation studies by taking recruitment, a more straightforward and salient form of peer recommendation, into account. This paper enriches theory by investigating the antecedents and consequences of game identification. This study clarifies the underlying mechanism of how game design influences peer recommendations and examines the interactions between game design and gamer orientation.
Preconditions to implementation of an integrated care process programme
Authors: Bångsbo Angela , Dunér Anna , Ivanoff Synneve Dahlin , Lidén Eva
Published: February 2021

Purpose

The purpose of this study was to investigate the preconditions of a full-scale implementation of an integrated care process programme for frail older people from the staff's understanding, commitment and ability to change their work procedures with comparisons over time and between organisations.

Design/methodology/approach

A repeated cross-sectional study was conducted in a hospital, municipal health and social care setting.

Findings

Staff commitment decreased to the importance of a permanent municipal contact from baseline compared to the 12-months follow-up (p = 0.02) and the six- and 12-months follow-up (p = 0.05), to the information transfer from emergency department from the six- to the 12-months follow-up (p = 0.04), to discharge planning at the hospital at six- and 12-months follow-up (p = 0.04) and towards discharge planning at home from baseline to the six-month follow-up (p = 0.04). Significant differences occurred between the organisations about information transfer from the emergency department (p = 0.01) and discharge planning at home (p = 0.03). The hospital staff were the most committed.

Practical implications

The results can guide the implementation of complex interventions in organisations with high-employee turnover and heavy workload.

Originality/value

The study design, allowing the comparison of implementation results over time and between organisations in a later phase, gives this study a unique perspective.