bluuebunny/crossref_metadata_2025 huggingface dataset:
Contrast-enhanced sonography with biomimetic lung surfactant nanodrops
Authors: Thomas Alec N. , Song Kang-Ho , Upadhyay Awaneesh , Papadopoulou Virginie , Ramirez David , Benninger Richard K. P. , Lowerison Matthew , Song Pengfei , Murray Todd W. , Borden Mark A.
Published: November 2020

Nanodrops comprising a perfluorocarbon liquid core can be acoustically vaporized into echogenic microbubbles for ultrasound imaging. Packaging the microbubble in its condensed liquid state provides distinct advantages, includingin situactivation of the acoustic signal, longer circulation persistence, and the advent of expanded diagnostic and therapeutic applications in pathologies which exhibit compromised vasculature. One obstacle to clinical translation is the inability of the limited surfactant present on the nanodrop to encapsulate the greatly expanded microbubble interface, resulting in ephemeral microbubbles with limited utility. In this study, we examine a biomimetic approach to stabilizing an expanding gas surface by employing the lung surfactant replacement, Beractant. Lung surfactant contains a suite of lipids and surfactant proteins that provides efficient shuttling of material from bilayer folds to the monolayer surface. We therefore hypothesized that Beractant would improve stability of acoustically vaporized microbubbles. To test this hypothesis, we characterized Beractant surface dilation mechanics and revealed a novel biophysical phenomenon of rapid interfacial melting, spreading and re-solidification. We then harnessed this unique spreading capability to increase the stability and echogenicity of microbubbles produced after acoustic droplet vaporization forin vivoultrasound imaging. Such biomimetic lung surfactant-stabilized nanodrops may be useful for applications in ultrasound imaging and therapy.

Graphical Abstract
Long-range gene regulation network of theMGMTenhancer in modulating glioma cell sensitivity to temozolomide
Authors: He Anshun , Chen Bohan , Bi Jinfang , Wang Wenbin , Chen Jun , Qian Yuyang , Shi Tengfei , Zhao Zhongfang , Shi Jiandang , Yang Hongzhen , Zhang Lei , Lu Wange
Published: November 2020

Acquired resistance to temozolomide (TMZ) is a major obstacle in glioblastoma treatment. MGMT, a DNA repair protein, and the methylation at its gene promoter, plays an important role in TMZ resistance. However, some evidences have suggested a MGMT-independent mechanisms underlying TMZ resistance. Here, we usedMGMTenhancer as a model and discovered that its deletion in glioma cells of lowMGMTexpression induced increased sensitivity to temozolomide. Analysis of a combination of RNA-seq and Capture Hi-C further suggested multiple long-range target genes regulated by theMGMTenhancer and that interactions may play important roles in glioma cell sensitivity to TMZ. This study reveals a novel mechanism of regulation of TMZ sensitivity in glioma cells.
Feedback inhibition of AMT1 NH4+-transporters mediated by CIPK15 kinase
Authors: Chen Hui-Yu , Chen Yen-Ning , Wang Hung-Yu , Liu Zong-Ta , Frommer Wolf B. , Ho Cheng-Hsun
Published: November 2020

Ammonium (NH4+), a key nitrogen form, becomes toxic when it accumulates to high levels. Ammonium transporters (AMTs) are the key transporters responsible for NH4+uptake. AMT activity is under allosteric feedback control, mediated by phosphorylation of a threonine in the cytosolic C-terminus (CCT). However, the kinases responsible for the NH4+-triggered phosphorylation remain unknown. In this study, a functional screen identified protein kinaseCBL-InteractingProteinKinase15 (CIPK15) as a negative regulator of AMT1;1 activity. CIPK15 was able to interact with several AMT1 paralogs at the plasma membrane. Analysis of AmTryoshka, an NH4+transporter activity sensor for AMT1;3 in yeast, and a two-electrode-voltage-clamp (TEVC) of AMT1;1 inXenopusoocytes showed that CIPK15 inhibits AMT activity. CIPK15 transcript levels increased when seedlings were exposed to elevated NH4+levels. Notably,cipk15knockout mutants showed higher15NH4+uptake and accumulated higher amounts of NH4+compared to the wild-type. Consistently,cipk15was hypersensitive to both NH4+and methylammonium but not nitrate (NO3−). Taken together, our data indicate that feedback inhibition of AMT1 activity is mediated by the protein kinase CIPK15 via phosphorylation of residues in the CCT to reduce NH4+-accumulation.
Environmental DNA as a management tool for tracking artificial waterhole use in savanna ecosystems
Authors: Farrell Maxwell J. , Govender Danny , Hajibabaei Mehrdad , van der Bank Michelle , Davies T. Jonathan
Published: November 2020

Game parks are the last preserve of many large mammals, and in savanna ecosystems, management of surface waters poses a conservation challenge. In arid and semi-arid regions, water can be a scarce resource during dry seasons and drought. Artificial waterholes are common in parks and reserves across Africa, but can alter mammal community composition by favoring drought intolerant species, with consequences for disease dynamics, and population viability of drought-tolerant species. Analysis of waterborne environmental DNA (eDNA) is increasingly used to inform conservation of rare and invasive species, and conduct large-scale biodiversity assessments. To explore the reliability of eDNA as an indicator of mammal waterhole use in savannas, we compare eDNA metabarcoding and camera traps for documenting artificial waterhole use in the Kruger National Park, South Africa, a global hotspot for mammal diversity. We show that eDNA metabarcoding can recover the majority of mammal species detected by camera traps, including a number of endangered species, but DNA signatures of mammal visitation are temporally limited, with best performance when tracking water-dependent large bodied mammals visiting within two days of sampling. Our results highlight limitation of eDNA based monitoring in these systems, including the lack of long-term eDNA persistence in small and highly utilized waterholes, and variability in detection rates among species. However, we demonstrate that eDNA-based approaches can be used to track mammals of conservation concern, and reflect patterns of recent waterhole use and co-occurrence across water-dependent species, both of which are crucial for making evidence-based decisions regarding water management and provisioning.
The translational landscape of SARS-CoV-2 and infected cells
Authors: Puray-Chavez Maritza , Lee Nakyung , Tenneti Kasyap , Wang Yiqing , Vuong Hung R. , Liu Yating , Horani Amjad , Huang Tao , Gunsten Sean P. , Case James B. , Yang Wei , Diamond Michael S. , Brody Steven L. , Dougherty Joseph , Kutluay Sebla B.
Published: November 2020

SARS-CoV-2 utilizes a number of strategies to modulate viral and host mRNA translation. Here, we used ribosome profiling in SARS-CoV-2 infected model cell lines and primary airway cells grown at the air-liquid interface to gain a deeper understanding of the translationally regulated events in response to virus replication. We find that SARS-CoV-2 mRNAs dominate the cellular mRNA pool but are not more efficiently translated than cellular mRNAs. SARS-CoV-2 utilized a highly efficient ribosomal frameshifting strategy in comparison to HIV-1, suggesting utilization of distinct structural elements. In the highly permissive cell models, although SARS-CoV-2 infection induced the transcriptional upregulation of numerous chemokines, cytokines and interferon stimulated genes, many of these mRNAs were not translated efficiently. Impact of SARS-CoV-2 on host mRNA translation was more subtle in primary cells, with marked transcriptional and translational upregulation of inflammatory and innate immune responses and downregulation of processes involved in ciliated cell function. Together, these data reveal the key role of mRNA translation in SARS-CoV-2 replication and highlight unique mechanisms for therapeutic development.
Intranasal fusion inhibitory lipopeptide prevents direct contact SARS-CoV-2 transmission in ferrets
Authors: de Vries Rory D. , Schmitz Katharina S. , Bovier Francesca T. , Noack Danny , Haagmans Bart L. , Biswas Sudipta , Rockx Barry , Gellman Samuel H. , Alabi Christopher A. , de Swart Rik L. , Moscona Anne , Porotto Matteo
Published: November 2020

Containment of the COVID-19 pandemic requires reducing viral transmission. SARS-CoV-2 infection is initiated by membrane fusion between the viral and host cell membranes, mediated by the viral spike protein. We have designed a dimeric lipopeptide fusion inhibitor that blocks this critical first step of infection for emerging coronaviruses and document that it completely prevents SARS-CoV-2 infection in ferrets. Daily intranasal administration to ferrets completely prevented SARS-CoV-2 direct-contact transmission during 24-hour co-housing with infected animals, under stringent conditions that resulted in infection of 100% of untreated animals. These lipopeptides are highly stable and non-toxic and thus readily translate into a safe and effective intranasal prophylactic approach to reduce transmission of SARS-CoV-2.

One-sentence summary

A dimeric form of a SARS-CoV-2-derived lipopeptide is a potent inhibitor of fusion and infectionin vitroand transmissionin vivo.
The bacterial toxin ExoU requires a host trafficking chaperone for transportation and to induce necrosis
Authors: Deruelle Vincent , Bouillot Stéphanie , Job Viviana , Taillebourg Emmanuel , Fauvarque Marie-Odile , Attrée Ina , Huber Philippe
Published: November 2020

Pseudomonas aeruginosais a causative agent in nosocomial infections, notably in ventilated or cystic fibrosis patients.P. aeruginosaisolates expressing the phospholipase ExoU, an effector of the type III secretion system, are the most pathogenic in clinics. Here, using a genome-wide screen, we discovered that ExoU toxicity requires DNAJC5, a host chaperone, to exert its necrotic activity. DNAJC5 is involved in an unconventional secretory pathway for misfolded proteins involving anterograde vesicular trafficking. DNAJC5-deficient human cells orDrosophilaflies knocked-down for the DNAJC5 orthologue were largely resistant to ExoU virulence. ExoU colocalized with DNAJC5-positive vesicles in the host cytoplasm. DNAJC5 mutations preventing vesicle trafficking - identified in adult neuronal ceroid lipofuscinosis, a human congenital disease - inhibited ExoU-dependent cell lysis. These results suggest that, once injected into the host cytoplasm, ExoU docks to DNAJC5-positive secretory vesicles to reach the plasma membrane, where its phospholipase activity is triggered by binding to PI(4,5)P2.
CaveThiovulaceaediffer metabolically and genomically from marine species
Authors: Bizic Mina , Brad Traian , Ionescu Danny , Barbu-Tudoran Lucian , Aerts Joost , Popa Radu , Zoccarato Luca , Ody Jessica , Flot Jean-François , Tighe Scott , Vellone Daniel , Sarbu Serban M.
Published: November 2020

Life in Movile Cave (Romania) relies entirely on carbon fixation by bacteria. The microbial community in the surface water of Movile Cave’s hypoxic air bells is dominated by large spherical-ovoid bacteria we identified asThiovulumsp. (Campylobacterota). These form a separate phylogenetic cluster within theThiovulaceae, consisting mostly of freshwater cave bacteria. We compared the closed genome of thisThiovulumto that of the marine strainThiovulumES, and to a genome we assembled from public data from the sulfidic Frasassi caves. The Movile and FrasassiThiovulumwere very similar, differing greatly from the marine strain. Based on their genomes, caveThiovulumcan switch between aerobic and anaerobic sulfide oxidation using O2and NO3-as electron acceptors, respectively. NO3-,is likely reduced to NH3via dissimilatory nitrate reduction to ammonia using periplasmic nitrate reductase (Nap) and hydroxylamine oxidoreductase. Thus,Thiovulum, is likely important to both S and N cycles in sulfidic subterranean aquatic ecosystems. Additionally, we suggest that the short peritrichous flagella-like structures typical ofThiovulumare type IV pili, for which genes were found in allThiovulumgenomes. These pili may play a role in veil formation, connecting adjacent cells and the exceptionally fast swimming of these bacteria.
Developmental Regulation of Mitotic Chromosome Formation Revealed by Condensin Reporter Mice
Authors: Taylor Gillian C A , Macdonald Lewis A , Bui Matilda , Scott Lucy , Christodoulou Ioannis , Bukowski-Wills Jimi , Papadopoulos Dimitrios K , Wood Andrew J
Published: November 2020

Withdrawal Note:

The authors have withdrawn their manuscript due to the discovery of artifacts that call into question key findings from the study. Both artifacts originate from cell-type differences that arose during sample processing, creating the impression that non-SMC subunits of condensin proteins were present at substantially higher levels in thymic T cells compared to bone marrow B cells or erythroblast cells. Based on data collected since the preprint was submitted, we no longer believe this to be true. The experimental artifacts do not affect the data contributed by the Papadopoulos laboratory (Figure 4).

The authors wish to make it clear that all data and experimental protocols in the original manuscript were accurately reported, and that the experimental artifacts which affect data interpretation were discovered during internal review, independently of peer review, and are being reported at the authors’ own instigation. They do not, to our knowledge, affect the interpretation of data from any other published work.

Due to the issues outlined above, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Human-specific expansion of 22q11.2 low copy repeats
Authors: Vervoort Lisanne , Dierckxsens Nicolas , Pereboom Zjef , Capozzi Oronzo , Rocchi Mariano , Shaikh Tamim H. , Vermeesch Joris R.
Published: November 2020

Segmental duplications or low copy repeats (LCRs) constitute complex regions interspersed in the human genome. They have contributed significantly to human evolution by stimulating neo- or sub-functionalization of duplicated transcripts. The 22q11.2 region carries eight LCRs (LCR22s). One of these LCR22s was recently reported to be hypervariable in the human population. It remains unknown whether this variability exists also in non-human primates. To assess the inter- and intra-species variability, wede novoassembled the region in non-human primates by a combination of optical mapping techniques. Orangutan carries three LCR22-mediated inversions of which one is the ancient haplotype since it is also present in macaque. Using fiber-FISH, lineage-specific differences in LCR22 composition were mapped. The smallest and likely ancient haplotype is present in the chimpanzee, bonobo and rhesus macaque. The absence of intra-species variation in chimpanzee indicates the LCR22-A expansion to be unique to the human population. Further, we demonstrate that LCR22-specific genes are expressed in both human and non-human primate neuronal cell lines and show expression of several primate LCR22 transcripts for the first time. The human-specificity of the expansions suggest an important role for the region in human evolution and adaptation.

Author summary

Low copy repeats or segmental duplications are DNA segments composed of various subunits which are duplicated across the genome. Due to the high level of sequence identity between these segments, homologous regions can misalign, resulting in reciprocal deletions and duplications, classified as genomic disorders. These regions are subject to structural variation in the human population. We recently detected extreme structural variation in one of the most complex segmental duplication regions of the human genome, the low copy repeats on chromosome 22 (LCR22s). Rearrangements between the LCR22s result in the 22q11.2 deletion/duplication syndrome, the most common human genomic disorder. However, it remains unknown whether this variability is human-specific. In this study, we investigated those LCR22s in several individuals of the different great apes and macaque. We show only the smallest haplotype is present without any intra-species variation in thePangenus, our closest ancestors. Hence, LCR22 expansions are human-specific, suggesting a role of these LCR22s in human evolution and adaptation and hypothesize the region contributes to the 22q11.2 deletion syndrome inter-patient phenotypic variability.
Prophages integrating into prophages: a mechanism to accumulate type III secretion effector genes and duplicate Shiga toxin-encoding prophages inEscherichia coli
Authors: Nakamura Keiji , Ogura Yoshitoshi , Gotoh Yasuhiro , Hayashi Tetsuya
Published: November 2020

Bacteriophages (or phages) play major roles in the evolution of bacterial pathogens via horizontal gene transfer. Multiple phages are often integrated in a host chromosome as prophages, not only carrying various novel virulence-related genetic determinants into host bacteria but also providing various possibilities for prophage-prophage interactions in bacterial cells. In particular,Escherichia colistrains such as Shiga toxin (Stx)-producingE. coli(STEC) and enteropathogenicE. coli(EPEC) strains have acquired more than 10 PPs (up to 21 PPs), many of which encode type III secretion system (T3SS) effector gene clusters. In these strains, some prophages are present at a single locus in tandem, which is usually interpreted as the integration of phages that use the same attachment (att) sequence. Here, we present prophages integrating into T3SS effector gene cluster-associated loci in prophages, which are widely distributed in STEC and EPEC. Some of the prophages integrated into prophages are Stx-encoding prophages and have induced the duplication of Stx-encoding phages in a single cell. The identifiedattsequences in prophage genomes are apparently derived from host chromosomes. In addition, two or three differentattsequences are present in some prophages, which results in the generation of prophage clusters in various complex configurations. These “prophages-in-prophages” represent a medically and biologically important type of inter-phage interaction that promotes the accumulation of T3SS effector genes in STEC and EPEC, the duplication of Stx-encoding prophages in STEC, and the conversion of EPEC to STEC and that may be distributed in other types ofE. colistrains as well as other prophage-rich bacterial species.

Author summary

Multiple prophages are often integrated in a bacterial host chromosome and some are present at a single locus in tandem. The most striking examples are Shiga toxin (Stx)-producing and enteropathogenicEscherichia coli(STEC and EPEC) strains, which usually contain more than 10 prophages (up to 21). Many of them encode a cluster of type III secretion system (T3SS) effector genes, contributing the acquisition of a large number of effectors (>30) by STEC and EPEC. Here, we describe prophages integrating into T3SS effector gene cluster-associated loci in prophages, which are widely distributed in STEC and EPEC. Two or three different attachment sequences derived from host chromosomes are present in some prophages, generating prophage clusters in various complex configurations. Of note, some of such prophages-in-prophages are Stx-encoding prophages and have induced the duplication of Stx-encoding prophages. Thus, these “prophages-in-prophages” represent an important inter-phage interaction as they can promote not only the accumulation of T3SS effectors in STEC and EPEC but also the duplication of Stx-encoding prophages and the conversion of EPEC to STEC.
Identification, Isolation, Propagation and Inactivation of SARS-CoV2 Isolated from Egypt
Authors: Seadawy M.G , Gad A.F , Elhoseny M.F , ELharty B.El , Shamel M.D
Published: November 2020

Severe Acute Respiratory Syndrome Coronavirus 2 causes the novel pandemic Pneumonia disease. It is a positive single strand ssRNA virus that infect human. COVID-19 appeared in Egypt in Feb 2020. The samples were taken from patients with COVID-19 symptoms at military hospital in Egypt and transported to the main chemical laboratories under all the biosafety measures according to WHO guidelines. All samples were tested with RT-PCR. Positive samples were cultured using VeroE6 cell lines. The propagated virus was isolated and inactivated. The isolated virus was sequenced using next generation sequencing and submitted into gene bank. This study provides an isolation, propagation and inactivation methodology which is valuable for production of inactivated vaccines against SARS-CoV2 in Egypt.
Canonical and noncanonical TGF-β signaling regulate fibrous tissue differentiation in the axial skeleton
Authors: Clayton Sade W. , Ban Ga I , Liu Cunren , Serra Rosa
Published: November 2020

Previously, we showed that embryonic deletion of TGF-β type 2 receptor in mouse sclerotome resulted in defects in fibrous connective tissues in the spine. Here we investigated how TGF-β regulates expression of fibrous markers: Scleraxis, Fibromodulin and Adamtsl2. We showed that TGF-β stimulated expression of Scleraxis mRNA by two hours and Fibromodulin and Adamtsl2 mRNAs by eight hours of treatment. Regulation of Scleraxis by TGF-β did not require new protein synthesis; however, protein synthesis was required for expression of Fibromodulin and Adamtsl2 indicating the necessity of an intermediate. We subsequently showed Scleraxis was a potential intermediate for TGF-β-regulated expression of Fibromodulin and Adamtsl2. The canonical effector Smad3 was not necessary for TGF-β-mediated regulation of Scleraxis. Smad3 was necessary for regulation of Fibromodulin and Adamtsl2, but not sufficient to super-induce expression with TGF-β treatment. Next, the role of several noncanonical TGF-β pathways were tested. We found that ERK1/2 was activated by TGF-β and required to regulate expression of Scleraxis, Fibromodulin, and Adamtsl2. Based on these results, we propose a model in which TGF-β regulates Scleraxis via ERK1/2 and then Scleraxis and Smad3 cooperate to regulate Fibromodulin and Adamtsl2. These results define a novel signaling mechanism for TGFβ-mediated fibrous differentiation in sclerotome.
Comparative molecular and immunoregulatory analysis of extracellular vesicles fromCandida albicansandCandida auris
Authors: Zamith-Miranda Daniel , Heyman Heino M. , Couvillion Sneha P. , Cordero Radames J. B. , Rodrigues Macio L. , Nimrichter Leonardo , Casadevall Arturo , Amatuzzi Rafaela F. , Alves Lysangela R. , Nakayasu Ernesto S. , Nosanchuk Joshua D.
Published: November 2020

Candida aurisis a recently described multidrug-resistant pathogenic fungus that is increasingly responsible for healthcare associated outbreaks across the world. Bloodstream infections of this fungus cause death in up to 70% of the cases. Aggravating this scenario,C. auris’disease-promoting mechanisms are poorly understood. Fungi release extracellular vesicles (EVs) carrying a broad range of molecules including proteins, lipids, carbohydrates, pigments, and RNA, many of which are virulence factors. Here, we carried out a comparative molecular characterization ofC. aurisandC. albicansEVs and evaluated their capacity to modulate effector mechanisms of host immune defense. Using proteomics, lipidomics, and transcriptomics, we found thatC. aurisreleased EVs with payloads that were strikingly different from EVs released byC. albicans. EVs released byC. aurispotentiated the adhesion of this yeast to an epithelial cell monolayer.C. aurisEVs also induced the expression of surface activation markers and cytokines by bone marrow-derived dendritic cells. Altogether, our findings show distinct profiles and properties of EVs released byC. aurisand byC. albicans,and highlight the potential contribution ofC. aurisEVs to the pathogenesis of this emerging pathogen.
Aurora-A phosphorylates splicing factors and regulates alternative splicing
Authors: Damodaran Arun Prasath , Gavard Olivia , Gagné Jean-Philippe , Rogalska Malgorzata Ewa , Mancini Estefania , Courtheoux Thibault , Cailloce Justine , Mereau Agnès , Poirier Guy G. , Valcárcel Juan , Watrin Erwan , Prigent Claude
Published: November 2020

Aurora-A kinase is well known to regulate progression through mitosis. However, the kinase also performs additional functions that could explain the failure of its inhibitors to be effective in cancer treatments. To identify these functions, we applied a proteomics approach to search for interactors of Aurora-A. We found a large number of proteins involved in pre-mRNA splicing, strongly suggesting an important role for Aurora-A in this biological process. Consistently, we first report the subcellular localization of Aurora-A in nuclear speckles, the storehouse of splicing proteins. We also demonstrate direct interaction of Aurora-A with RRM domain-containing splicing factors such as hnRNP and SR proteins and their phosphorylationin vitro. Further, RNA-sequencing analysis following pharmacological inhibition of Aurora-A resulted in alternative splicing changes corresponding to 505 genes, including genes with functions regulated by Aurora-A kinase. Finally, we report enrichment of RNA motifs within the alternatively spliced regions affected by Aurora-A kinase inhibition which are bound by Aurora-A interacting splicing factors, suggesting that Aurora-A regulates alternative splicing by modulating the activity of these interacting splicing factors. Overall our work identified Aurora-A as a novel splicing kinase and for the first time, describes a broad role of Aurora-A in regulating alternative splicing.
WNT responsive SUMOylation of ZIC5 exerts multiple effects on transcription to promote murine neural crest cell development
Authors: Ali Radiya G. , Bellchambers Helen M. , Warr Nicholas , Ahmed Jehangir N. , Barratt Kristen S. , Neill Kieran , Diamand Koula E. M. , Arkell Ruth M.
Published: November 2020

Zinc finger of the cerebellum (Zic) proteins act as classical transcription factors to promote transcription of theFoxd3gene during neural crest cell specification. Additionally, they can act as co-factors that bind TCF molecules to repress WNT/β-catenin dependent transcription without contacting DNA. Here, we show ZIC activity at the neural plate border is influenced by WNT-dependent SUMOylation. In a high WNT environment, a lysine within the highly conserved ZF-NC domain of ZIC5 is SUMOylated, which decreases formation of the TCF/ZIC co-repressor complex and shifts the balance towards transcription factor function. The modification is criticalin vivo, as a ZIC5 SUMO-incompetent mouse strain exhibits neural crest specification defects. This work reveals the function of the ZIC ZF-NC domain, providesin vivovalidation of target protein SUMOylation, and demonstrates that WNT/β-catenin signalling directs transcription at non-TCF DNA binding sites. Furthermore, it can explain how WNT signals convert a broad domain ofZicectodermal expression into a restricted domain of neural crest cell specification.
GAK and PRKCD are positive regulators of PRKN-independent mitophagy
Authors: Munson Michael J. , Mathai Benan J. , Trachsel Laura , Ng Matthew Yoke Wui , de la Ballina Laura Rodriguez , Schultz Sebastian W. , Aman Yahyah , Lystad Alf H. , Singh Sakshi , Singh Sachin , Wesche Jørgen , Fang Evandro F. , Simonsen Anne
Published: November 2020

The mechanisms involved in programmed or damage-induced removal of mitochondria by mitophagy in response to different stimuli remains elusive. Here, we have screened for regulators of PRKN-independent mitophagy using an siRNA library targeting 197 proteins containing lipid interacting domains. We identify Cyclin G-associated kinase (GAK) and Protein Kinase C Delta (PRKCD) as novel regulators of PRKN-independent mitophagy, with both being dispensable for PRKN-dependent mitophagy and starvation-induced autophagy. We demonstrate that the kinase activity of both GAK and PRKCD are required for efficient mitophagyin vitro, that PRKCD is present on mitochondria, and that PRKCD is required for ULK1/ATG13 recruitment to early autophagic structures. Importantly, we demonstratein vivorelevance for both kinases in the regulation of basal mitophagy. Knockdown of GAK homologue (gakh-1) inC.elegansor PRKCD homologues in zebrafish led to significant inhibition of basal mitophagy, highlighting the evolutionary relevance of these kinases in mitophagy.
Novel de novo ARCN1 intronic variant causes rhizomelic short stature with microretrognathia and developmental delay
Authors: Tidwell Timothy , Deshotel Malia , Palumbos Janice , Miller Chris , Bayrak-Toydemir Pinar , Carey John C.
Published: November 2020

The archain 1 (ARCN1) gene encodes the coatomer subunit delta protein and is a component of the COPI coatomer complex, which is involved in retrograde vesical trafficking from the Golgi complex to the endoplasmic reticulum. Variants in ARCN1 have recently been associated with rhizomelic short stature with microcephaly, microretrognathia, and developmental delay. Here we report a 3.5-yr-old boy with microcephaly, global developmental delay, and multiple congenital abnormalities and the ARCN1-related syndrome caused by a novel de novo intronic variant. Whole-exome sequencing of the proband and his parents was utilized to determine the genetic origin of the patient's disorder and identified a de novo variant, NM_001655.5:c.654-15A > G, in the ARCN1 gene. Follow-up functional characterization of mRNA from the patient demonstrated that this variant creates a splicing defect of the ARCN1 mRNA. ARCN1-related syndrome represents an emerging disorder of developmental delay, and this report represents the sixth described patient. Despite the few instances reported in literature, the phenotype is consistent between our patient and previously reported individuals.
Turnover intent of new workers: social exchange perspectives
Authors: Jabutay Felicito Angeles , Rungruang Parisa
Published: November 2020

Purpose

This paper aims to investigate the impact of task interdependence and leader–member exchange, as social exchange variables, on affective commitment and turnover intent of new workers in an industry with high attrition rates. In addition, the paper examines the mediating effects of affective commitment.

Design/methodology/approach

The present study drew insights from the literature to formulate hypotheses that link the two social exchange variables on affective commitment and turnover intent. Through the utilization of the data collected from 441 call center agents working for eight call centers in the Philippines, the hypotheses were tested and analyzed using structural equation modeling.

Findings

The results reveal that task interdependence and leader–member exchange are positive antecedents of affective commitment and negative predictors of turnover intent. Further analysis reveals that affective commitment fully mediates the effects of the two social exchange variables on turnover intent.

Practical implications

The results imply that call centers can help improve new workers' affective commitment and reduce their turnover intent through job designs that can facilitate high task interdependence. Furthermore, training team leaders or supervisors to develop leadership styles that are more focused on people and relationships may also increase the agents' commitment and reduce their quit intention.

Originality/value

This paper is the first to demonstrate that social exchange variables can also impact the affective commitment and turnover intent of new workers in an industry known to have heavy supervisorial monitoring, high demands in terms of work quotas and high turnover rates.
Tracing objects of a lost room in suburbia
Authors: Kacmaz Erk Gul , Balcioglu Tevfik
Published: November 2020

Purpose

Bringing product design and architectural design together, this article looks into the extraordinary use of everyday objects in urban and suburban spaces in The Lost Room mini-television series (2006). The study questions the accepted meanings of products and spaces in relation to their physicality, perception and use. Through multi-layered analysis of the relationship between objects, (architectural and suburban/urban) spaces and their users, the article opens up a discussion about the purpose, meaning and influence of designed products and places.

Design/methodology/approach

In this context, this qualitative research makes use of moving images (as representations of products and spaces) to propose a critique of contemporary design via (sub-)urban design practices.

Findings

Using irony and metaphor to question the habit of object possession, accumulation and fetishism, the series challenges blind loyalty to contemporary beliefs. The Lost Room is not concerned with new forms or new designs. Instead, it forces the audience to consider the meaning of both objects and spaces in relation to one another. By transforming our understanding of space, the series also reveals humans' spatial limitations. The Lost Room is a unique small screen “product” in which people's relationship to the designed world is interrogated by having mass-produced objects and the built environment constantly in the foreground.

Originality/value

Film analysis from a design perspective is not new; however, this is the first time The Lost Room is brought to the attention of architects and designers via scholarly work. Film theorists and cinemagoers may also benefit from the unique design perspective outlined in the article.
Consumers in local food markets: from adoption to market co-creation?
Authors: Bentsen Kristin , Pedersen Per Egil
Published: November 2020

Purpose

The purpose of this paper is to explore the consumer adoption literature on local food. This study discusses the applicability of traditional models of adoption and diffusion to understand new phenomena such as the development of local food networks.

Design/methodology/approach

A systematic review of the literature on the adoption and diffusion of local food systems was conducted.

Findings

A total of three main challenges within the literature on the adoption and diffusion of local food are identified: the lack of a clear definition of what constitutes local food, divergent market assumptions and divergent consumer assumptions. In addition, this study points to the need for new perspectives on consumer adoption and diffusion of local food practices.

Originality/value

This paper provides an overview of current local food research streams and contributes to the literature on consumer adoption and diffusion of local food consumption.
Content analysis of food safety implications in online flour-handling recipes
Authors: Barrett Tressie , Feng Yaohua
Published: November 2020

Purpose

Numerous food recalls and outbreaks were associated with wheat flour in recent years. Few consumers are cognizant of food safety risks associated with raw flour. The purpose of this study is to evaluate the food safety information and flour-handling behaviors presented in popular food blog recipes and in YouTube videos using cookie, cookie dough and egg noodle recipes as examples.

Design/methodology/approach

Eighty-five blog recipes and 146 videos were evaluated. Blog author and video host food-handling experience was classified as professional or nonprofessional. Food safety information and food-handling behaviors were evaluated for adherence to government and scientific recommendations.

Findings

Blog authors and video hosts demonstrated higher awareness of food safety risks associated with raw eggs compared to raw flour, which only translated into better adherence with recommended food-handling behaviors during ingredient addition steps. Cross-contamination from adding raw flour to the product was observed in 25% of videos, whereas cross-contamination from hosts adding raw shell eggs was observed 3% of videos. Blog authors and video hosts did not recommend or demonstrate handwashing after handling raw shell eggs nor raw flour, and fewer than 5% provided recommendations for cleaning work surfaces. Heat treatment methods to convert raw flour into ready-to-eat products were mentioned by 24% of blog authors and 18% of video hosts; however, the recommendations were not scientifically validated.

Originality/value

This study demonstrates the need to develop educational interventions that increase blog authors' and video hosts' awareness of risks associated with raw flour and that translate this knowledge into practiced behaviors.
Entrepreneurial leadership and employee innovative behavior: an examination through multiple theoretical lenses
Authors: Iqbal Amjad , Nazir Tahira , Ahmad Muhammad Shakil
Published: November 2020

Purpose

The purpose of this research is to determine the relationship between entrepreneurial leadership and employee innovative behavior and examine mediating role of affective commitment, creative self-efficacy and psychological safety in this relationship.

Design/methodology/approach

Using cross-sectional research design, data were collected from 343 employees of information technology (IT) service firms in Pakistan. Partial least squares–structural equation modeling (PLS-SEM) technique was applied to test the proposed research model.

Findings

The findings reveal that entrepreneurial leadership is strongly and positively related to employee innovative behavior. Moreover, affective commitment, creative self-efficacy and psychological safety simultaneously mediate this relationship.

Practical implications

This study uncovers the important role of entrepreneurial leadership in driving employee innovative behavior in high-tech services industry. Findings of this study suggest that by practicing entrepreneurial behaviors, managers can enhance employees' affective commitment, creative self-efficacy and psychological safety, which invoke employees to demonstrate innovative behavior leading toward improved innovation performance at organizational level.

Originality/value

This research makes novel contribution to entrepreneurial leadership theory by using competing theoretical perspectives and subsequently providing more nuanced picture of the contrasting mechanisms that transmit the impact of entrepreneurial leadership on employee innovative behavior.
Outcomes of talent management: the role of perceived equity
Authors: Malik Amina R. , Singh Parbudyal
Published: November 2020

Purpose

To date, the effects of two approaches – inclusive and exclusive – to talent management (TM) on employee outcomes are largely unexplored. This paper explores the role of perceived equity and theoretically examines the process through which these TM programs impact employee outcomes.

Design/methodology/approach

This paper draws on the job demands-resources model and equity theory and proposes a typology of employee outcomes in the context of different approaches to TM.

Findings

Based on the theoretical framework, the paper argues that in the context of both inclusive and exclusive TM, perceived equity is a valuable resource that motivates employees and results in favourable outcomes.

Research limitations/implications

Future empirical studies should test the propositions put forth in this paper. The multilevel research design would allow for an in-depth analysis of organisational contexts, and qualitative studies using in-depth interviews can provide greater insights into employees' experiences and perspectives of TM programs.

Practical implications

The paper presents implications for managers and human resource (HR) and TM professionals regarding how to get the most out of their TM programs. These implications are important since employee equity perceptions can influence the effectiveness of TM programs.

Originality/value

In this paper, the authors add to the literature by examining the role of employee equity perceptions in the context of inclusive and exclusive TM and to highlight how perceived (in)equity could lead to negative consequences, even among high potential (HiPo) employees.
Supervisor-subordinate relationships and employee performance appraisals: a multi-source investigation in Croatia
Authors: Varma Arup , Zilic Ivana , Katou Anastasia , Blajic Branimir , Jukic Nenad
Published: November 2020

Purpose

The purpose of this paper is to empirically examine supervisor-subordinate relationships and their impact on performance appraisal in Croatia. Specifically, we were interested in examining how supervisor-subordinate relationships impact subordinate perceptions of performance evaluation and the subordinate's reactions to the performance evaluation.

Design/methodology/approach

This paper uses matched data from a sample of supervisors and subordinates (n = 53) in a leading organization in the hospitality industry in Croatia, as well as objective performance appraisal data to examine the impact of supervisor-subordinate relationships on subordinate reactions to performance appraisal.

Findings

The key findings of this study include (1) supervisor trustworthiness determines the quality of their relationship with subordinates and leads to interpersonal liking, and (2) supervisor-subordinate relationship quality has a significant impact on subordinate reactions to performance appraisal process and outcomes.

Research limitations/implications

The overall sample size (n = 53) of this study is small, and limits our ability to make generalizations beyond a point. Also, since the sample included only Croatian individuals, the findings maybe an artifact of the fact that they all hold similar values. Future studies should examine these relationships in supervisor-subordinate dyads comprised of individuals of different cultural backgrounds.

Practical implications

Supervisors should attempt to have high quality relationships with most, if not all, subordinates, as this would lead to higher acceptance of the performance appraisal process, which can impact future performance. Also, trustworthiness is closely related to the subordinate's perception of the quality of relationship he/she shares with the supervisor.

Originality/value

This is the first known paper to empirically study performance appraisal processes and relationships in Croatia, which also included both supervisor and subordinate perspectives.
Job search strategies of recent university graduates: prevalence and effectiveness
Authors: Varshavskaya Elena , Podverbnykh Ulyana
Published: November 2020

Purpose

The purpose of the paper is to analyse the prevalence and effectiveness of methods and strategies for job searches amongst recent graduates of Russian universities.

Design/methodology/approach

The empirical analysis is carried out on data from the Russian Graduate Survey 2016, which is representative of individuals graduating during 2010–2015. The sample included 12,370 individuals. The empirical approach combined standard descriptive statistics, factor and regression analysis (multiple logit regression).

Findings

Results show that the most common strategies are a combined strategy that involves the use of formal and informal methods, as well as “pure” informal strategies – applying to relatives and friends or contacting employers. The most effective strategies are job searches with the help of relatives and friends, by contacting employers and with the help of educational organisations. The choice of job search strategy is determined by the expected return in terms of the likelihood of finding a job.

Practical implications

The paper increases understanding of graduate job search behaviour. The results can be used by multiple stakeholders in higher education to better prepare students for job seeking.

Originality/value

This research, based on a large field survey of recent university graduates, provides the first estimates of use of job search strategies and their effectiveness for Russian university graduates.
How internal transparency impacts organizational resilience
Authors: Al Balushi Mohammed
Published: November 2020

Purpose

Research on transparency has been concerned mainly with external transparency, leaving internal transparency understudied. In particular, there is a lack of empirical research on the relationship between internal transparency and organizational resilience. This paper aims at investigating how internal transparency impacts organizational resilience in a public entity. It also examines how (quality) management systems impact internal transparency, and thus organizational resilience.

Design/methodology/approach

The research is based on semi-structured interviews covering the relevant topics. A total of 32 interviews were undertaken between January and May 2018.

Findings

The findings indicate that internal transparency contributes to better preparedness to adverse conditions by enhancing the ability to cumulate, locate and share knowledge. Similarly, management systems improve internal transparency through the enhancement of communication flow, use of indicators and accretion of a database.

Originality/value

The paper is the first, as evident from the literature review, to investigate how internal transparency impacts organizational resilience. Hence, it sheds light on a very important aspect of the effective management of quality, risk and reliability. It is also one of the first papers to examine the mediating role of (quality) management systems in organizational resilience.
Optimal preventive maintenance level for a repairable product under warranty subject to multimode failure process
Authors: Ullah Azmat , Ayat Muhammad , Rehman Hakeem Ur , Batala Lochan Kumar
Published: November 2020

Purpose

The purpose of this paper is to develop a model that determines whether how much effort of preventive maintenance action is worthwhile for the consumer over the post-sale product life cycle of a repairable complex product where the product is under warranty and subject to stochastic multimode failure process, that is, damaging failure and light failure with different probabilities.

Design/methodology/approach

The expected life cycle cost is designed for a warranted product from the consumer perspective. The product failure is quantified with failure rate function, which is the number of failures incurred over the product life cycle. The authors consider the failure rate function reduction method in their model where the scale parameter of a failure rate function is maximized by applying the optimal preventive maintenance level. The scale parameter of any failure distribution refers to the meantime to failure (MTTF). The first-order condition is applied with respect to the maintenance level in order to achieve the convexity of the nonlinear function of the expected life cycle cost function.

Findings

The authors have found analytically the close form of the preventive maintenance level, which can be used to find the optimal reduced form of the failure rate function of the product and the minimum product expected life cycle cost under the given condition of multimode stochastic failure process. The authors have suggested different maintenance policies to consumers in order to implement the proposed preventive maintenance model under different conditions. A numerical example further illustrated the analytical model by considering the Weibull distribution.

Practical implications

The consumer may use this study in the accurate modeling of the life cycle cost of a product that is under warranty and fails with a multimode failure process. Also, the suggested preventive maintenance approach of this study helps the consumer in making appropriate maintenance decisions such as to minimize the expected life cycle cost of a product.

Originality/value

This study proposes an accurate estimation of a life cycle cost for a product that is under the support of warranty and fails with multimode. Furthermore, for such a kind of product, which is under warranty and fails with multimode, this study suggests a new preventive maintenance approach that assures the minimum expected life cycle cost.