bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Age-Specific Patterns of Cyclic Gene Expression Revealed by Tunicate Transcriptome Atlas
Authors: Voskoboynik Yotam , Glina Aidan , Kowarsky Mark , Anselmi Chiara , Neff Norma F , Ishizuka Katherine J , Palmeri Karla J , Rosental Benyamin , Gordon Tal , Quake Stephen R , Weissman Irving L , Ben-Shlomo Rachel , Sahoo Debashis , Voskoboynik Ayelet
Published: December 2020

Expression levels of circadian clock genes, which regulate 24-hour rhythms of behavior and physiology, have been shown to change with age. However, a study holistically linking aging and circadian gene expression is missing. Using the colonial chordateBotryllus schlosseri, we combined transcriptome sequencing and stem cell-mediated aging phenomena to test how circadian gene expression changes with age. This revealed thatB. schlossericlock and clock-controlled genes oscillate organism-wide, with daily, age-specific amplitudes and frequencies. These age-related, circadian patterns persist at the tissue level, where dramatic variations in cyclic gene expression of tissue profiles link to morphological and cellular aging phenotypes. Similar cyclical expression differences were found in hundreds of pathways associated with known hallmarks of aging, as well as pathways that were not previously linked to aging. The atlas we developed points to alterations in circadian gene expression as a key regulator of aging.

One Sentence Summary

The Ticking Clock: Systemic changes in circadian gene expression correlates with wide-ranging phenotypes of aging
Legionella pneumophila’s Tsp is important for surviving thermal stress in water and inside amoeba
Authors: Saoud Joseph , Mani Thangadurai , Faucher Sébastien P.
Published: December 2020

Legionella pneumophila(Lp) is an inhabitant of natural and man-made water systems where it replicates within amoebae and ciliates and survives within biofilms. WhenLp-contaminated aerosols are breathed in,Lpwill enter the lungs and infect human alveolar macrophages, causing a severe pneumonia known as Legionnaires Disease.Lpis often found in hot water distribution systems (HWDS), which are linked to nosocomial outbreaks. Heat treatment is used to disinfect HWDS and reduce the concentration ofLp. However,Lpis often able to recolonize these water systems, indicating an efficient heat-shock response. Tail-specific proteases (Tsp) are typically periplasmic proteases implicated in degrading aberrant proteins in the periplasm and important for surviving thermal stress. In this paper, we show that Tsp, encoded by thelpg0499gene inLpPhiladelphia-1, is important for surviving thermal stress in water and for optimal infection of amoeba when a shift in temperature occurs during intracellular growth. Tsp is expressed in the post-exponential phase but repressed in the exponential phase. Thecis-encoded small regulatory RNA Lpr17 shows opposite expression, suggesting that it represses translation oftsp. In addition,tspis regulated by CpxR, a major regulator inLp, in a Lpr17-independent manner. Deletion of CpxR also reduced the ability ofLpto survive heat shock. In conclusion, this study shows that Tsp is an important factor for the survival and growth ofLpin water systems.

IMPORTANCE

Legionella pneumophila(Lp) is a major cause of nosocomial and community-acquired pneumonia.Lpis found in water systems including hot water distribution systems. Heat treatment is a method of disinfection often used to limitLp’s presence in such systems; however, the benefit is usually short term asLpis able to quickly recolonize these systems. Presumably,Lprespond efficiently to thermal stress, but so far not much is known about the genes involved. In this paper, we show that the Tail-specific protease (Tsp) and the two-component system CpxRA are required for resistance to thermal stress, whenLpis free in water and when it is inside host cells. Our study identifies critical systems for the survival ofLpin its natural environment under thermal stress.
Age and axon-specific forms of cortical remyelination by divergent populations of NG2-glia
Authors: Chapman Timothy W. , Olveda Genaro E. , Pereira Elizabeth , Hill Robert A.
Published: December 2020

Myelin is critical for neural circuit function and its destruction is widespread in neurodegenerative disease and aging. In these conditions, homeostatic repair mechanisms initiate oligodendrocyte replacement by resident progenitor cells called NG2-glia. To investigate the cellular dynamics of this repair we developed a novel demyelination model by combining intravital myelin imaging with a targeted single-cell ablation technique called 2Phatal. Oligodendrocyte 2Phatal activated a stereotyped degeneration cascade which triggered remyelination by local NG2-glia. Remyelination efficiency was dependent on initial myelin patterning and dynamic imaging revealed rapid repair mechanisms resulting in near-seamless transitions between myelin loss and repair. A subset of morphologically complex NG2-glia executed this remyelination, pointing towards unrecognized functional diversity within this population. Age-related demyelination mirrored the degenerative cascade observed with 2Phatal, while remyelination in aging was defective due to failed oligodendrogenesis. Thus, oligodendrocyte 2Phatal revealed cellular diversity within the oligodendrocyte lineage and uncovered novel forms of rapid remyelination.
PopAmaranth: A population genetic genome browser for grain amaranths and their wild relatives
Authors: Gonçalves-Dias José , Stetter Markus G
Published: December 2020

The last decades of genomic, physiological, and population genetic research have accelerated the understanding and improvement of a numerous crops. The transfer of methods to minor crops could accelerate their improvement if knowledge is effectively shared between disciplines. Grain amaranth is an ancient nutritious pseudocereal from the Americas that is regaining importance due to its high protein content and favorable amino acid and micronutrient composition. To effectively combine genomic and population genetic information with molecular genetics, plant physiology, and use it for interdisciplinary research and crop improvement, an intuitive interaction for scientists across disciplines is essential. Here, we present PopAmaranth, a population genetic genome browser, which provides an accessible representation of the genetic variation of the three grain amaranth species (A. hypochondriacus, A. cruentus, andA. caudatus) and two wild relatives (A. hybridusandA. quitensis) along theA. hypochondriacusreference sequence. We performed population-scale diversity and selection analysis from whole-genome sequencing data of 88 curated genetically and taxonomically unambiguously classified accessions. We incorporate the domestication history of the three grain amaranths to make an evolutionary perspective for candidate genes and regions available. We employ the platform to show that genetic diversity in the water stress-related MIF1 gene declined during amaranth domestication and provide evidence for convergent saponin reduction between amaranth and quinoa. These examples show that our tool enables the detailed study of individual genes, provides target regions for breeding efforts and can enhance the interdisciplinary integration of population genomic findings across species. PopAmaranth is available through amaranthGDB at amaranthgdb.org/popamaranth.html

Significance

Sharing population genetic results between disciplines can facilitate interdisciplinary research and accelerate the improvement of crops. Since the onset of genome sequencing online genome browser platforms have provide access to features of an organisms genetic information. Rarely this has been extended to population-wide summary statistics for evolutionary hypothesis testing. We implemented a population genetic genome browser PopAmaranth for three grain amaranth species and their two wild relatives. The intuitive and user-friendly interface of PopA-maranth makes the genetic diversity of the species complex available to broad audience of biologists across disciplines. We show how our tool can be used to study convergence across distant genera and find signals of past selection in domestication and stress related genes. Community platforms and genome browsers are an integrative element of numerous study systems. PopAmaranth can serve as template for other research communities to integrate and share their results.
Identification of a Novel Susceptibility Marker for SARS-CoV-2 Infection in Human Subjects and Risk Mitigation with a Clinically Approved JAK Inhibitor in Human/Mouse Cells
Authors: Spalinger Marianne R. , Hai Rong , Li Jiang , Santos Alina N. , Nordgren Tara M. , Tremblay Michel L. , Eckmann Lars , Hanson Elaine , Scharl Michael , Wu Xiwei , Boland Brigid S. , McCole Declan F.
Published: December 2020

Coronavirus disease (COVID-19), caused by SARS-CoV-2, has affected over 65 million individuals and killed over 1.5 million persons (December 8, 2020;www.who.int)1. While fatality rates are higher among the elderly and those with underlying comorbidities2, host factors that promote susceptibility to SARS-CoV-2 infection and severe disease are poorly understood. Although individuals with certain autoimmune/inflammatory disorders show increased susceptibility to viral infections, there is incomplete knowledge of SARS-CoV-2 susceptibility in these diseases.3–7We report that the autoimmunePTPN2risk variant rs1893217 promotes expression of the SARS-CoV-2 receptor, ACE2, and increases cellular entry mediated by SARS-CoV-2 spike protein. Elevated ACE2 expression and viral entry were mediated by increased JAK-STAT signalling, and were reversed by the JAK inhibitor, tofacitinib. Collectively, our findings uncover a novel risk biomarker for increased expression of the SARS-CoV-2 receptor and viral entry, and identify a clinically approved therapeutic agent to mitigate this risk.
An interactive viral genome evolution network analysis system enabling rapid large-scale molecular tracing of SARS-CoV-2
Authors: Ling Yunchao , Cao Ruifang , Qian Jiaqiang , Li Jiefu , Zhou Haokui , Yuan Liyun , Wang Zhen , Zheng Guangyong , Zhao Guoping , Li Yixue , Wang Zefeng , Zhang Guoqing
Published: December 2020

Comprehensive analyses of viral genomes can provide a global picture on SARS-CoV-2 transmission and help to predict the oncoming trends of pandemic. This molecular tracing is mainly conducted through extensive phylogenetic network analyses. However, the rapid accumulation of SARS-CoV-2 genomes presents an unprecedented data size and complexity that has exceeded the capacity of existing methods in constructing evolution network through virus genotyping. Here we report a Viral genome Evolution Network Analysis System (VENAS), which uses Hamming distances adjusted by the minor allele frequency to construct viral genome evolution network. The resulting network was topologically clustered and divided using community detection algorithm, and potential evolution paths were further inferred with a network disassortativity trimming algorithm. We also employed parallel computing technology to achieve rapid processing and interactive visualization of >10,000 viral genomes, enabling accurate detection and subtyping of the viral mutations through different stages of Covid-19 pandemic. In particular, several core viral mutations can be independently identified and linked to early transmission events in Covid-19 pandemic. As a general platform for comprehensive viral genome analysis, VENAS serves as a useful computational tool in the current and future pandemics.
A vacuolar hexose transport is required for xylem development in the inflorescence stem of Arabidopsis
Authors: Aubry Emilie , Hoffmann Beate , Vilaine Françoise , Gilard Françoise , Klemens Patrick A.W. , Guérard Florence , Gakière Bertrand , Neuhaus H. Ekkehard , Bellini Catherine , Dinant Sylvie , Hir Rozenn Le
Published: December 2020

In higher plants, the development of the vascular system is controlled by a complex network of transcription factors. However, how nutrient availability in the vascular cells affects their development remains to be addressed. At the cellular level, cytosolic sugar availability is regulated mainly by sugar exchanges at the tonoplast through active and/or facilitated transport. InArabidopsis thaliana, among the tonoplastic transporters,SWEET16andSWEET17genes have been previously localized in the vascular system. Here, using a reverse genetic approach, we propose that sugar exchanges at the tonoplast, regulated by SWEET16, are important for xylem cell division as revealed in particular by the decreased number of xylem cells in theswt16mutant and the expression of SWEET16 at the procambium-xylem boundary. In addition, we demonstrate that transport of hexoses mediated by SWEET16 and/or SWEET17 is required to sustain the formation of the xylem secondary cell wall. This result is in line with a defect in the xylem cell wall composition as measured by FTIR in theswt16swt17double mutant and by upregulation of several genes involved in secondary cell wall synthesis. Our work therefore supports a model in which xylem development is partially dependent on the exchange of hexoses at the tonoplast of xylem-forming cells.
DDK regulates replication initiation by controlling the multiplicity of Cdc45-GINS binding to Mcm2-7
Authors: De Jesús-Kim Lorraine , Friedman Larry J. , Ramsoomair Christian , Gelles Jeff , Bell Stephen P.
Published: December 2020

The committed step of eukaryotic DNA replication occurs when the replicative Mcm2-7 helicase pairs that license each replication origin are activated. Helicase activation requires the recruitment of Cdc45 and GINS to Mcm2-7, forming Cdc45-Mcm2-7-GINS complexes (CMGs). Using single-molecule biochemical assays to monitor CMG formation, we found that Cdc45 and GINS are recruited to loaded Mcm2-7 in two stages. Initially, Cdc45 and GINS are individually recruited to unstructured Mcm2-7 N-terminal tails in a Dbf4-dependent kinase (DDK)-dependent manner, forming Cdc45-tail-GINS intermediates (CtGs). The multiple phosphorylation sites on the Mcm2-7 tails promote DDK-dependent modulation of the number of CtGs formed per Mcm2-7. In a second, inefficient event, a subset of CtGs transfer their Cdc45 and GINS components to form CMGs. Importantly, higher CtG multiplicity results in increased frequency of CMG formation. Our findings reveal molecular mechanisms sensitizing helicase activation to DDK levels with implications for the control of replication origin efficiency and timing.
Spatio-temporal dynamics of intra-host variability in SARS-CoV-2 genomes
Authors: Pathak Ankit K. , Mishra Gyan Prakash , Uppili Bharathram , Walia Safal , Fatihi Saman , Abbas Tahseen , Banu Sofia , Ghosh Arup , Kanampalliwar Amol , Jha Atimukta , Fatima Sana , Aggarwal Shifu , Dhar Mahesh Shanker , Marwal Robin , Radhakrishnan V. S. , Ponnusamy Kalaiarasan , Kabra Sandhya , Rakshit Partha , Bhoyar Rahul C. , Jain Abhinav , Divakar Mohit Kumar , Imran Mohamed , Faruq Mohammed , Sowpati Divya Tej , Thukral Lipi , Raghav Sunil K. , Mukerji Mitali
Published: December 2020

During the course of the COVID-19 pandemic, large-scale genome sequencing of SARS-CoV-2 has been useful in tracking its spread and in identifying Variants Of Concern (VOC). Besides, viral and host factors could contribute to variability within a host that can be captured in next-generation sequencing reads as intra-host Single Nucleotide Variations (iSNVs). Analysing 1, 347 samples collected till June 2020, we recorded 18, 146 iSNV sites throughout the SARS-CoV-2 genome. Both, mutations in RdRp as well as APOBEC and ADAR mediated RNA editing seem to contribute to the differential prevalence of iSNVs in hosts. Noteworthy, 41% of all unique iSNVs were reported as SNVs by 30th September 2020 in samples submitted to GISAID, which increased to ∼80% by 30th June 2021. Following this, analysis of another set of 1, 798 samples sequenced in India between November 2020 and May 2021 revealed that majority of the Delta (B.1.617.2) and Kappa (B.1.617.1) variations appeared as iSNVs before getting fixed in the population. We also observe hyper-editing events at functionally critical residues in Spike protein that could alter the antigenicity and may contribute to immune escape. Thus, tracking and functional annotation of iSNVs in ongoing genome surveillance programs could be important for early identification of potential variants of concern and actionable interventions.

GRAPHICAL ABSTRACT
Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project
Authors: Lopera-Maya E.A. , Kurilshikov A. , van der Graaf A. , Hu S. , Andreu-Sánchez S. , Chen L. , Vich Vila A. , Gacesa R. , Sinha T. , Collij V. , Klaassen M.A.Y. , Bolte L.A. , Brandao Gois M.F. , Neerincx P.B.T. , Swertz M.A. ,   LifeLines Cohort Study, Harmsen H.J.M. , Wijmenga C. , Fu J. , Weersma R.K. , Zhernakova A. , Sanna S.
Published: December 2020

Host genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function within the Dutch Microbiome Project, a population cohort of 7,738 individuals from the northern Netherlands. Two robust, study-wide significant (p<1.89×10-10) signals near theLCTandABOgenes were found to affect multiple microbial taxa and pathways, and were replicated in two independent cohorts. TheLCTlocus associations were modulated by lactose intake, while those atABOreflected participant secretor status determined byFUT2genotype. Eighteen other loci showed suggestive evidence (p<5×10-8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.
Loss of p32 triggers energy deficiency and impairs goblet cell differentiation in ulcerative colitis
Authors: Sünderhauf Annika , Hicken Maren , Schlichting Heidi , Skibbe Kerstin , Ragab Mohab , Raschdorf Annika , Hirose Misa , Schäffler Holger , Bokemeyer Arne , Bettenworth Dominik , Savitt Anne G. , Perner Sven , Ibrahim Saleh , Peerschke Ellinor I. , Ghebrehiwet Berhane , Derer Stefanie , Sina Christian
Published: December 2020

Cell differentiation in the colonic crypt is driven by a metabolic switch from glycolysis to mitochondrial oxidation. Mitochondrial and goblet cell (GC) dysfunction have been attributed to the pathology of ulcerative colitis (UC). We hypothesized that p32/gC1qR/HABP1, which critically maintains oxidative phosphorylation, is involved in GC differentiation and hence in the pathogenesis of UC. In UC patients in remission, colonic GC differentiation was significantly decreased compared to controls in a p32-dependent manner. Plasma/serum lactate and colonic pAMPK level were increased, pointing at high glycolytic activity and energy deficiency. Consistently,p32silencing in mucus-secreting HT29-MTX cells abolished butyrate-induced differentiation and induced a shift towards glycolysis. In mitochondrial respiratory chain complex V-deficient mice, colonic p32 expression correlated with loss of differentiated GCs, resulting in a thinner mucus layer. Conversely, feeding mice an isocaloric glucose-free, high-protein diet increased mucosal energy supply that promoted colonic p32 level, GC differentiation and mucus production. We here describe a new molecular mechanism linking mucosal energy deficiency in UC to impaired p32-dependent GC differentiation that may be therapeutically prevented by nutritional intervention.
Allele Mining in Diverse Accessions ofUrochloaandMegathyrsusspp. Tropical Grasses to Improve Forage Quality and Reduce Environmental Impact
Authors: Hanley SJ , Pellny TK , de Vega JJ , Castiblanco V , Arango J , Eastmond PJ , Heslop-Harrison JS , Mitchell RAC
Published: December 2020

The C4Urochloaspp (syn.Brachiaria) andMegathyrsus maximus(syn.Panicum maximum) are used as pasture for cattle across vast areas in tropical agriculture systems in Africa and South America. A key target for variety improvement is forage quality: enhanced digestibility could decrease amount of land required per unit production and enhanced lipid content could decrease methane emissions from cattle. For these traits, loss-of-function (LOF) alleles in known gene targets are predicted to improve them, making a reverse genetics approach of allele mining feasible. We studied allelic diversity of 20 target genes (11 for digestibility, 9 for lipid content) in 104 accessions selected to represent genetic diversity and ploidy levels ofU. brizantha,U. decumbens, U. humidicola, U. ruziziensisandM. maximum. We used RNAseq and then bait-capture DNA-seq to improve gene models in aU. ruziziensisreference genome to assign polymorphisms with high confidence. We found 953 non-synonymous polymorphisms across all genes and accessions; within these, we identified 7 putative LOF alleles with high confidence, including ones in the non-redundant SDP1 and BAHD01 genes present in diploid and tetraploid accessions. These LOF alleles could respectively confer increased lipid content and digestibility if incorporated into a breeding programme.

Highlight

We found gene variants in a collection of tropical grasses that could help reduce environmental impact of cattle production.
UbiB proteins regulate cellular CoQ distribution
Authors: Kemmerer Zachary A. , Robinson Kyle P. , Schmitz Jonathan M. , Paulson Brett R. , Jochem Adam , Hutchins Paul D. , Coon Joshua J. , Pagliarini David J.
Published: December 2020

Coenzyme Q (CoQ, ubiquinone) is a redox-active lipid essential for many core metabolic processes in mitochondria, including oxidative phosphorylation1-3. While lesser appreciated, CoQ also serves as a key membrane-embedded antioxidant throughout the cell4. However, how CoQ is mobilized from its site of synthesis on the inner mitochondrial membrane to other sites of action remains a longstanding mystery. Here, using a combination of yeast genetics, biochemical fractionation, and lipid profiling, we identify two highly conserved but poorly characterized mitochondrial proteins, Ypl109c (Cqd1) and Ylr253w (Cqd2), that reciprocally regulate this process. Loss of Cqd1 skews cellular CoQ distribution away from mitochondria, resulting in markedly enhanced resistance to oxidative stress caused by exogenous polyunsaturated fatty acids (PUFAs), whereas loss of Cqd2 promotes the opposite effects. The activities of both proteins rely on their atypical kinase/ATPase domains, which they share with Coq8—an essential auxiliary protein for CoQ biosynthesis. Overall, our results reveal new protein machinery central to CoQ trafficking in yeast and lend new insights into the broader interplay between mitochondrial and cellular processes.
Transcription factors drive opposite relationships between gene age and tissue specificity in male and femaleDrosophilagonads
Authors: Witt Evan , Svetec Nicolas , Benjamin Sigi , Zhao Li
Published: December 2020

Evolutionarily young genes are usually preferentially expressed in the testis across species. While it is known that older genes are generally more broadly expressed than younger genes, the properties that shaped this pattern are unknown. Older genes may gain expression across other tissues uniformly, or faster in certain tissues than others. UsingDrosophilagene expression data, we confirmed previous findings that younger genes are disproportionately testis-biased and older genes are disproportionately ovary-biased. We found that the relationship between gene age and expression is stronger in the ovary than any other tissue, and weakest in testis. We performed ATAC-seq onDrosophilatestis and found that while genes of all ages are more likely to have open promoter chromatin in testis than in ovary, promoter chromatin alone does not explain the ovary-bias of older genes. Instead, we found that upstream transcription factor (TF) expression is highly predictive of gene expression in ovary, but not in testis. In ovary, TF expression is more predictive of gene expression than open promoter chromatin, whereas testis gene expression is similarly influenced by both TF expression and open promoter chromatin. We propose that the testis is uniquely able to expresses younger genes controlled by relatively few TFs, while older genes with more TF partners are broadly expressed with peak expression most likely in ovary. The testis allows widespread baseline expression that is relatively unresponsive to regulatory changes, whereas the ovary transcriptome is more responsive to trans-regulation and has a higher ceiling for gene expression.
INO80 promotes H2A.Z occupancy to regulate cell fate transition in pluripotent stem cells
Authors: Yu Hongyao , Wang Jiajia , Lackford Brad , Bennett Brian , Li Jian-liang , Hu Guang
Published: December 2020

The INO80 chromatin remodeler is involved in many chromatin-dependent cellular functions. However, its role in pluripotency and cell fate transition is not fully defined. We examined the impact of Ino80 deletion in the naïve and primed pluripotent stem cells. We found that Ino80 deletion had minimal effect on self-renewal and gene expression in the naïve state, but led to cellular differentiation and de-repression of developmental genes in the transition toward and maintenance of the primed state. Mechanistically, INO80 pre-marked gene promoters that would adopt the H3K4me3 and H3K27me3 bivalent histone modifications. It promoted H2A.Z occupancy at these future bivalent domains to facilitate H3K27me3 installation and maintenance as well as downstream gene repression. Thus, INO80-dependent H2A.Z occupancy is a critical a licensing step for bivalency and poised gene expression in pluripotent stem cells. Our results uncovered an unexpected function of INO80 in H2A.Z deposition and gene repression, and an epigenetic mechanism by which chromatin remodeling, histone variant and modification coordinately control cell fate.
SARS-CoV-2 inhibition in human airway epithelial cells using a mucoadhesive, amphiphilic chitosan that may serve as an anti-viral nasal spray
Authors: Pyrć Krzysztof , Milewska Aleksandra , Duran Emilia Barreto , Botwina Paweł , Lopes Rui , Arenas-Pinto Alejandro , Badr Moutaz , Mellor Ryan , Kalber Tammy L. , Fernandes-Reyes Delmiro , Schätzlein Andreas G. , Uchegbu Ijeoma F.
Published: December 2020

There are currently no cures for coronavirus infections, making the prevention of infections the only course open at the present time. The COVID-19 pandemic has been difficult to prevent, as the infection is spread by respiratory droplets and thus effective, scalable and safe preventive interventions are urgently needed. We hypothesise that preventing viral entry into mammalian nasal epithelial cells may be one way to limit the spread of COVID-19. Here we show that N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (GCPQ), a positively charged polymer that has been through an extensive Good Laboratory Practice toxicology screen, is able to reduce the infectivity of SARS-COV-2 in A549ACE2+and Vero E6 cells with a log removal value of −3 to −4 at a concentration of 10 – 100 μg/ mL (p < 0.05 compared to untreated controls) and to limit infectivity in human airway epithelial cells at a concentration of 500 μg/ mL (p < 0.05 compared to untreated controls). GCPQ is currently being developed as a pharmaceutical excipient in nasal and ocular formulations. GCPQ’s electrostatic binding to the virus, preventing viral entry into the host cells, is the most likely mechanism of viral inhibition. Radiolabelled GCPQ studies in mice show that at a dose of 10 mg/ kg, GCPQ has a long residence time in mouse nares, with 13.1% of the injected dose identified from SPECT/CT in the nares, 24 hours after nasal dosing. With a no observed adverse effect level of 18 mg/ kg in rats, following a 28-day repeat dose study, clinical testing of this polymer, as a COVID-19 prophylactic is warranted.
mTOR inhibition acts as an unexpected checkpoint in p53-mediated tumor suppression
Authors: Kon Ning , Ou Yang , Wang Shang-Jui , Li Huan , Rustgi Anil K. , Gu Wei
Published: December 2020

Here, we showed that the acetylation-defective p53-4KR mice, lacking the ability of cell cycle arrest, senescence, apoptosis, and ferroptosis, were tumor prone but failed to develop early-onset tumors. By identifying a novel p53 acetylation site at lysine K136, we found that simultaneous mutations at all five acetylation sites (p53-5KR) diminished its remaining tumor suppression function. Moreover, the embryonic lethality caused by the deficiency of mdm2 was fully rescued in the background of p535KR/5KR, but not p534KR/4KR background. p53-4KR retained the ability to suppress mTOR function but this activity was abolished in p53-5KR cells. Notably, the early-onset tumor formation observed in p535KR/5KR and p53-null mice was suppressed upon the treatment of the mTOR inhibitor. These results suggest that p53-mediated mTOR regulation plays an important role in both embryonic development and tumor suppression, independent of cell cycle arrest, senescence, apoptosis, and ferroptosis.
Pioneer-like factor GAF cooperates with PBAP (SWI/SNF) and NURF (ISWI) to regulate transcription
Authors: Judd Julius , Duarte Fabiana M. , Lis John T.
Published: December 2020

Transcriptionally silent genes must be activated throughout development. This requires nucleosomes be removed from promoters and enhancers to allow transcription factor (TF) binding and recruitment of coactivators and RNA polymerase II (Pol II). Specialized pioneer TFs bind nucleosome-wrapped DNA to perform this chromatin opening by mechanisms that remain incompletely understood. Here, we show that GAGA factor (GAF), a Drosophila pioneer-like factor, functions with both SWI/SNF and ISWI family chromatin remodelers to allow recruitment of Pol II and entry to a promoter-proximal paused state, and also to promote Pol II's transition to productive elongation. We found that GAF interacts with PBAP (SWI/SNF) to open chromatin and allow Pol II to be recruited. Importantly, this activity is not dependent on NURF as previously proposed; however, GAF also synergizes with NURF downstream from this process to ensure efficient Pol II pause release and transition to productive elongation, apparently through its role in precisely positioning the +1 nucleosome. These results demonstrate how a single sequence-specific pioneer TF can synergize with remodelers to activate sets of genes. Furthermore, this behavior of remodelers is consistent with findings in yeast and mice, and likely represents general, conserved mechanisms found throughout eukarya.
Evidence of widespread, independent sequence signature for transcription factor cobinding
Authors: Zhou Manqi , Li Hongyang , Wang Xueqing , Guan Yuanfang
Published: December 2020

Transcription factors (TFs) are the vocabulary that genomes use to regulate gene expression and phenotypes. The interactions among TFs enrich this vocabulary and orchestrate diverse biological processes. Although simple models identify open chromatin and the presence of TF motifs as the two major contributors to TF binding patterns, it remains elusive what contributes to the in vivo TF cobinding landscape. In this study, we developed a machine learning algorithm to explore the contributors of the cobinding patterns. The algorithm substantially outperforms the state-of-the-field models for TF cobinding prediction. Game theory–based feature importance analysis reveals that, for most of the TF pairs we studied, independent motif sequences contribute one or more of the two TFs under investigation to their cobinding patterns. Such independent motif sequences include, but are not limited to, transcription initiation–related proteins and known TF complexes. We found the motif sequence signatures and the TFs are rarely mutual, corroborating a hierarchical and directional organization of the regulatory network and refuting the possibility of artifacts caused by shared sequence similarity with the TFs under investigation. We modeled such regulatory language with directed graphs, which reveal shared, global factors that are related to many binding and cobinding patterns.
Forecasting of COVID-19 epidemic size in four high hitting nations (USA, Brazil, India and Russia) by Fb-Prophet machine learning model
Authors: Battineni Gopi , Chintalapudi Nalini , Amenta Francesco
Published: December 2020

Purpose

As of July 30, 2020, more than 17 million novel coronavirus disease 2019 (COVID-19) cases were registered including 671,500 deaths. Yet, there is no immediate medicine or vaccination for control this dangerous pandemic and researchers are trying to implement mathematical or time series epidemic models to predict the disease severity with national wide data.

Design/methodology/approach

In this study, the authors considered COVID-19 daily infection data four most COVID-19 affected nations (such as the USA, Brazil, India and Russia) to conduct 60-day forecasting of total infections. To do that, the authors adopted a machine learning (ML) model called Fb-Prophet and the results confirmed that the total number of confirmed cases in four countries till the end of July were collected and projections were made by employing Prophet logistic growth model.

Findings

Results highlighted that by late September, the estimated outbreak can reach 7.56, 4.65, 3.01 and 1.22 million cases in the USA, Brazil, India and Russia, respectively. The authors found some underestimation and overestimation of daily cases, and the linear model of actual vs predicted cases found a p-value (<2.2e-16) lower than the R2 value of 0.995.

Originality/value

In this paper, the authors adopted the Fb-Prophet ML model because it can predict the epidemic trend and derive an epidemic curve.
Communication scheduling data generation for pre-configured IMA network
Authors: Zhao Zhen , Fan Zhiyong , Sun Yigang , Liu Zhexu
Published: December 2020

Purpose

In modern integrated modular avionics (IMA), it plays an important role to guarantee safety and reliability of the system. The safety and reliability of communication scheduling plays a crucial role in this IMA platforms-based network system. To verify the safety and reliability of the communication scheduling in this network, sufficient and typical test data must be generated to input into the network, obtain and evaluate the corresponding output.

Design/methodology/approach

To generate communication scheduling data, this paper presents an iterative communication scheduling data generation algorithm for a configured network of IMA platforms. First, the algorithm generates all possible communication schedules for the first timestamp. Then, constraint is introduced to decrease the quantity of communication schedules to improve the efficiency. The communication schedules are gradually extended to the second timestamp until the final timestamp, i.e. length of communication scheduling sequence.

Findings

To verify the efficiency and feasibility of the algorithm, a model is built based on the architecture analysis and design language (AADL) by mapping the correlation time of generated communication scheduling data into task properties. Schedulability is analyzed by loading this model into AADL Inspector. The simulation result illustrates that the proposed algorithm is efficient and feasible.

Practical implications

The proposed method can provide data support for communication scheduling test for the network of IMA platforms.

Originality/value

A constraint-based iterative communication scheduling data generation algorithm is proposed for the network of IMA platforms automatically.
Do consumers really recognise a distinct quality hierarchy amongst PDO sparkling wines? The answer from experimental auctions
Authors: Galletto Luigi , Caracciolo Francesco , Boatto Vasco , Barisan Luigino , Franceschi Deborah , Lillo Marica
Published: December 2020

Purpose

Consumer likeability and willingness to pay (WTP) for two Italian sparkling wines, (Conegliano Valdobbiadene Prosecco DOCG and Prosecco DOC) are evaluated through a non-hypothetical Becker-DeGroot-Marschak (BDM) auction during a wine-tasting experiment. The purpose of this paper is to estimate individual WTP and relate it to likeability for both wines, with and without supplying additional information on their features.

Design/methodology/approach

Data were collected in May–June 2019 from a sample of 99 consumers in Northern Italy. A non-hypothetical BDM auction in a wine-tasting experiment was implemented.

Findings

The results show that the additional information plays a significant role in widening the WTP gap between the two geographical indications (GIs), while the blind tasting narrows this gap. The “superiority” of the Conegliano Valdobbiadene Prosecco DOCG is confirmed but relies more on its better reputation than its better taste.

Research limitations/implications

The authors are aware of two main limitations in the study. The first is the territorial composition of the consumer sample. The second is the selection of the Prosecco bottles used in the experiment. The results are considered pioneering and need to be verified by additional experiments with different consumer and bottle samples.

Practical implications

Promotional suggestions for the Tutelary Consortia of the two GIs stem from the results. The Prosecco DOC should primarily stress its likeability, while the Conegliano Valdobbiadene Prosecco DOCG should primarily emphasise the reasons for its “superiority”.

Originality/value

To the best of the authors' knowledge, no previous study has related likeability and WTP for similar GI wines produced in contiguous areas. Moreover, the current research has applied a non-hypothetical BDM auction in a wine-tasting experiment.
Welfare effects of vegetable producers' inclusiveness in supply chain coordination: direct effects and spillovers
Authors: Liang Qiao , Li Lin , Bai Rongrong
Published: December 2020

Purpose

The purpose of this paper is to estimate the effect of vegetable producers' inclusiveness in supply chain coordination on vegetable production performance and potential spillover effect on farm and non-farm income.

Design/methodology/approach

A comprehensive dataset comprised of 410 paired vegetable producers in China is applied. Propensity score matching (PSM) estimation method is used to control for the selection bias problem.

Findings

The empirical results indicate that contracting farming does not have significant effect on yield or profit of vegetable production, but promote producers to obtain quality certification. In comparison, cooperative membership has positive effects on the yield, profit and quality certification of producers. Additionally, cooperatives generate positive spillover effects on members' farm and non-farm income, though the results are sensitive to unobserved factors. The inclusion of spillover effects helps to find out the potential unobserved effects which are neglected by most studies and design better policies to promote the development of agricultural companies and farmer cooperatives.

Originality/value

First, empirical evidence is provided for theories regarding the roles of different supply chain coordination modes on producers. Second, the analysis on evaluating the effects of supply chain coordination also considers the spillover effect on the farming of other products and even non-farm work of involved producers. Third, a unique dataset comprised of 420 paired vegetable producers, based on an extensive survey is built.
Representation of women managers in hospitality and tourism: a content analysis of related magazine articles
Authors: Nagar Komal
Published: December 2020

Purpose

This study aims to investigate the representation of women managers through a content analysis of related magazine articles within the hospitality industry in the Maldives. Evidence suggests an increase in the number of working women, yet there is relative neglect toward identifying issues involving women in the industry.

Design/methodology/approach

Both qualitative and quantitative approaches were used to content-analyze the narrative on the sampled articles from a Maldives-based hospitality magazine, Hotelier Maldives. Qualitative content analysis and quantitative methods report on the challenges faced by women managers and reasons for their success based on the narratives.

Findings

This study revealed that although women managers are underrepresented in management, there has been a broad increase in the participation of women within the industry. This study falsified the perception that gender is a limiting factor to hold senior positions in the hospitality industry and that increased participation of women managers may be driven by the changing social and cultural contexts.

Originality/value

This study is one of the first to examine how women managers are represented in hospitality magazines. Despite its relevance, previous tourism research has not focused on this kind of measurement.
Generic skill profiles of future accountants and auditors – moving beyond attributes
Authors: Barac Karin , Plant Kato , Kunz Rolien , Kirstein Marina
Published: December 2020

Purpose

This study investigates perceptions regarding generic skills future entry-level accountants and auditors will require. Such soft or pervasive skills are necessary to operate effectively in the future world of work. Prior research mainly explores generic skills from an attribute-based perspective, while this paper combines it with an activity-based perspective in generic skill profiles of accountants and auditors.

Design/methodology/approach

Following a mixed methods research approach through focus group discussions and a survey involving more than 3,000 professional accountants and/or auditors, the study uses data from the Southern African region (South Africa, Zimbabwe and Namibia) to determine views on the competency needs of future accountants and auditors. An exploratory factor analysis was conducted to determine whether categories of generic skills for future entry-level accountants and auditors differ.

Findings

Four generic skills factors emerged as essential for future entry-level chartered accountants (CAs): digital, decision-making, organisational and business acumens. Three generic skill factors emerged for future registered auditors (RAs): digital, practice and commercial acumens. The results show that generic skill profiles of CAs and RAs, who are members of an accounting body differ and that both the context, related to an activity-based perspective, and individual or internal abilities, related to an attribute-based perspective, matter.

Research limitations/implications

The study extends generic skill theory by identifying broad categories of generic skills (referred to as acumens) for future accountants and auditors.

Practical implications

Insights from this paper facilitate a comprehensive understanding of the generic skill profile approach, combining attribute-based and activity-based perspectives, and this could assist accounting educators, practitioners and professional bodies to better prepare entry-level accounting and audit professionals for the workplace.

Originality/value

The study identifies broad categories (digital, decision-making, organisational, business, practice and commercial acumens) within generic skill profiles of CAs and RAs and shows that generic skills do not operate independently and should be viewed as an interdependent set or constellation of competencies.
Market-oriented corporate digital responsibility to manage data vulnerability in online banking
Authors: Liyanaarachchi Gajendra , Deshpande Sameer , Weaven Scott
Published: December 2020

Purpose

This conceptual paper explores gaps in bank privacy protection practices and advocates for banks to integrate market-oriented (MO) approaches in their corporate digital responsibility (CDR) initiatives to minimize consumer data vulnerability.

Design/methodology/approach

To apply MO in CDR, this study recommends adoption of a behavior change framework comprising of the co-creation, build and engage (CBE) model and proposes the creation of consumer segments based on generational cohort and tailoring strategies through motivation, opportunity and ability (MOA) model to manage vulnerability.

Findings

The study specifies that managing consumer data vulnerability requires a unique strategy different from conventional service delivery. A holistic approach is recommended by integrating corporate digital responsibility as a pivotal element of organizational strategy and by positioning vulnerable customers as a critical stakeholder.

Originality/value

The paper contributes to the research in corporate social responsibility (CSR), privacy and data vulnerability in the banking sector in two prominent ways: first, the study demonstrates the importance of MO as a premise to develop a novel version of CDR called market-oriented digital responsibility (MODR). The study considers MODR as a strategy to reposition vulnerable consumers as a key stakeholder, and, second, the study proposes an innovative set of consumer segments based on data vulnerability and introduces a data vulnerability growth model (DVGM) connecting vulnerability with age.
Removal behavior of methylene blue from graphene oxide/gluten composite material: kinetics, isotherms and thermodynamics
Authors: Zhang Xiaoping , Li Yanhui , Li Meixiu , Du Qiuju , Li Hong , Wang Yuqi , Wang Dechang , Wang Cuiping , Sui Kunyan , Li Hongliang , Xia Yanzhi , Yu Yuanhai
Published: December 2020

Purpose

In order to discover a new adsorbent that can be used to purify dye wastewater in the textile and apparel industry, a novel type of graphene oxide/gluten composite material using an improved acid bath coagulation method was synthesized, which can remove methylene blue in an aqueous environment.

Design/methodology/approach

After experimentally compounding different ratios of graphene oxide and gluten, the graphene oxide/gluten composite material with 20% graphene oxide content and superlative adsorption effect was chosen. The synthesized material was characterized by different techniques such as FT-IR and SEM, indicating the microstructure of the material and the success of the composite. Various factors were considered, namely, the influence of temperature, dosage, pH and contact time. The isotherms, kinetics and thermodynamic parameters were successively discussed.

Findings

The qmax value of 214.29 mg/g of the material was higher compared to the general sorbent, thus, the graphene oxide/gluten composite material was a suitable sorbent for methylene blue removal. Overall, the graphene oxide/gluten composite material can be considered as an effectual and prospective adsorbent to remove methylene blue in the textile and apparel industrial effluent.

Originality/value

Graphene oxide is a potentially excellent sorbent. However, the high dispersibility of GO is detrimental to adsorption, it disperses rapidly in an aqueous solution making separation and recovery difficult. The high load capacity and recyclability of gluten as a colloid make it a suitable carrier for fixing GO. Studies on the combination of GO and GT into composite adsorption material and for the removal of dyes from dyeing wastewater have not been reported. The composite material research on GO and GT can provide new ideas for the research of these kinds of materials and contribute to its wider and convenient application in wastewater treatment.