bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid genomic evolution inBrassica rapawith bumblebee selection in experimental evolution
Authors: Frachon Léa , Schiestl Florian P.
Published: December 2021

Background

Insect pollinators shape rapid phenotypic evolution of traits related to floral attractiveness and plant reproductive success. However, the underlying genomic changes remain largely unknown despite their importance in predicting adaptive responses to natural or to artificial selection. Based on a nine-generation experimental evolution study with fast cyclingBrassica rapaplants adapting to bumblebees, we investigate the genomic evolution associated with the previously observed parallel phenotypic evolution. In this current evolve and resequencing (E&R) study, we conduct a genomic scan of the allele frequency changes along the genome in bumblebee-pollinated and hand-pollinated plants and perform a genomic principal component analysis (PCA).

Results

We highlight rapid genomic evolution associated with the observed phenotypic evolution mediated by bumblebees. Controlling for genetic drift, we observe significant changes in allelic frequencies at multiple loci. However, this pattern differs according to the replicate of bumblebee-pollinated plants, suggesting putative non-parallel genomic evolution. Finally, our study underlines an increase in genomic differentiation implying the putative involvement of multiple loci in short-term pollinator adaptation.

Conclusions

Overall, our study enhances our understanding of the complex interactions between pollinator and plants, providing a steppingstone towards unravelling the genetic basis of plant genomic adaptation to biotic factors in the environment.
Layer 1 NDNF+ Interneurons Control Bilateral Sensory Processing in a Layer-dependent Manner
Authors: Vighagen Rasmus , Gesuita Lorenzo , Damilou Angeliki , Cavaccini Anna , Banterle Lila , Steenhuis Veerle , Karayannis Theofanis
Published: December 2021

Bilateral sensory information is indispensable for navigating the world. In most mammals, signals sensed by either side of the midline will ultimately reach the cortex where they will be integrated for perception and appropriate action selection. Even though information transferred across the hemispheres is routed through the corpus callosum, how and which microcircuits are key in integrating it is not well understood. Here we identify an essential role for layer 1 NDNF+ inhibitory cells of mice in integrating bilateral whisker-evoked information in an NMDA receptor-dependent manner. Direct connections from the contralateral cortex and the ipsilateral side activate NDNF+ neurons, which subsequently inhibit the late spiking activity of underlying layer 2/3 neurons, but not layer 5. Our results identify a feed-forward regulatory pathway for bilateral cortical sensory processing of upper layer cortical neurons actuated via layer 1 NDNF+ interneurons.
Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development
Authors: Kim Junil , Rothová Michaela Mrugala , Madan Esha , Rhee Siyeon , Weng Guangzheng , Palma António M. , Liao Linbu , David Eyal , Amit Ido , Hajkarim Morteza Chalabi , Gutiérrez-García Andrés , Fisher Paul B. , Brickman Joshua M. , Gogna Rajan , Won Kyoung Jae
Published: December 2021

Development of multicellular organisms is orchestrated by persistent cell-cell communication between neighboring partners. Direct interaction between different cell types can induce molecular signals that dictate lineage specification and cell fate decisions. Current single cell RNAseq (scRNAseq) technology cannot adequately analyze cell-cell contact-dependent gene expression, mainly due to the loss of spatial information. To overcome this obstacle and resolve cell-cell contact-specific gene expression during embryogenesis, we performed RNA sequencing of physically interacting cells (PIC-seq) and assessed them alongside similar single cell transcriptomes derived from developing mouse embryos between embryonic day (E) 7.5 and E9.5. Analysis of the PIC-seq data identified novel gene expression signatures that were dependent on the presence of specific neighboring cell types. Our computational predictions, validated experimentally, demonstrated that neural progenitor (NP) cells overexpress Lhx5 and Nkx2-1 genes, when exclusively interacting with the definitive endoderm (DE) cell. Moreover, there was a reciprocal impact on the transcriptome of the DE cells, as they tend to overexpress Rax and Gsc genes when in contact with the NP cells. Using individual cell transcriptome data, we formulated a means of computationally predicting the impact of one cell type on the transcriptome of its neighboring cell types. We have further developed a distinctive spatial-tSNE to display the pseudo-spatial distribution of cells in a 2-dimensional space. In summary, we describe an innovative approach to study contact-specific gene regulation during embryogenesis with potential broader implication in other physiologically relevant processes.

Significance

Physical contact between neighboring cells is known to induce transcriptional changes in the interacting partners. Accurate measurement of these cell-cell contact based influences on the transcriptome is a very difficult experimental task. However, determining such transcriptional changes will highly enhance our understanding for the developmental processes. Current scRNAseq technology isolates the tissue into individual cells, making it hard to determine the potential transcriptomic changes due to its interacting partners. Here, we combined PIC-seq and computational algorithms to identify cell-type contact dependent transcriptional profiles focusing on endoderm development. We have computationally identified and experimentally validated specific gene expression patterns depending upon the presence of specific neighboring cell types. Our study suggests a new way to study cell-cell interactions for embryogenesis.
Glucose-1,6-bisphosphate, a key metabolic regulator, is synthesized by a distinct family of α-phosphohexomutases widely distributed in prokaryotes
Authors: Neumann Niels , Friz Simon , Forchhammer Karl
Published: December 2021

The reactions of α-D-phosphohexomutases (αPHM) are ubiquitous, key to primary metabolism and essential for several processes in all domains of life. The functionality of these enzymes relies on an initial auto-phosphorylation step which requires the presence of α-D-glucose-1,6-bisphosphate (Glc-1,6-BP). While well investigated in vertebrates, the origin of this activator compound in bacteria is unknown. Here we show that the Slr1334 protein from the unicellular cyanobacterium Synechocysitis sp. PCC 6803 is a Glc-1,6-BP-synthase. Biochemical analysis revealed that Slr1334 efficiently converts fructose-1,6-bisphosphate (Frc-1,6-BP) and α-D-glucose-1-phosphate/α-D-glucose-6-phosphate into Glc-1,6-BP and also catalyzes the reverse reaction. As inferred from phylogenetic analysis, the slr1334 product belongs to a primordial subfamily of αPHMs that is present especially in deeply branching bacteria and also includes human commensals and pathogens. Remarkably, the homologue of Slr1334 in the human gut bacterium Bacteroides salyersiae catalyzes the same reaction, suggesting a conserved and essential role for the members of this αPHM subfamily.
No evidence that LSD microdosing affects recall or the balance between distracter resistance and updating
Authors: Fallon Sean James
Published: December 2021

The effect of low doses (<=20 μg) of LSD on working memory, in the absence of altered states of consciousness, remain largely unexplored. Given its possible effects on serotonin 5-HT2A receptors and dopaminergic signalling, it could be hypothesised that LSD microdoses modulate working memory recall. Moreover, in line with computational models, LSD microdoses could exert antagonistic effects on distracter resistance and updating. Here, we tested this hypothesis in a randomised double-blind, placebo-controlled study comparing three different LSD microdoses (5 μg, 10μg and 20μg) with placebo. After capsule administration, participants performed a modified delay-match-to-sample (DMTS) dopamine-sensitive task. The standard DMTS task was modified to include novel items in the delay period between encoding and probe. These novel items either had to be ignored or updated into working memory. There was no evidence that LSD microdoses affected the accuracy or efficiency of working memory recall and there was no evidence for differential effects on ignoring or updating. Due to the small sample of participants, these results are preliminary and larger studies are required to establish whether LSD microdoses affect short-term recall.
Differential mobility and self-association of Arc/Arg3.1 in the cytoplasm and nucleus of living cells
Authors: Hedde Per Niklas , Barylko Barbara , Binns Derk D. , Jameson David M. , Albanesi Joseph P.
Published: December 2021

Arc, also known as Arg3.1, is an activity-dependent immediate-early gene product that plays essential roles in memory consolidation. A pool of Arc is located in the postsynaptic cytoplasm, where it promotes AMPA receptor endocytosis and cytoskeletal remodeling. However, Arc is also found in the nucleus, a major portion being associated with promyelocytic leukemia nuclear bodies (PML-NBs). Nuclear Arc has been implicated in epigenetic control of gene transcription associated with learning and memory. In this study, we use a battery of fluorescence nanoimaging approaches to characterize the behavior of Arc in living cells. Our results indicate that in the cytoplasm, Arc exists predominantly as monomers and dimers associated with slowly diffusing particles. In contrast, nuclear Arc is almost exclusively monomeric and displays a higher diffusivity than cytoplasmic Arc. We further show that Arc moves freely and rapidly between PML-NBs and the nucleoplasm, and that its movement within PML-NBs is relatively unobstructed.
Spectral distribution dynamics across different attentional priority states
Authors: Pietrelli Mattia , Samaha Jason , Postle Bradley R.
Published: December 2021

Anticipatory covert spatial attention improves performance on tests of visual detection and discrimination, and shifts are accompanied by decreases and increases of alpha-band power at EEG electrodes corresponding to the attended and unattended location, respectively. Although the increase at the unattended location is often interpreted as an active mechanism (e.g., inhibiting processing at the unattended location), most experiments cannot rule out the alternative possibility that it is a secondary consequence of selection elsewhere. To adjudicate between these accounts, we designed a Posner-style cuing task in which male and female human participants made orientation judgments of targets appearing at one of four locations: up, down, right, or left. Critically, trials were blocked such that within a block the locations along one meridian alternated in status between attended and unattended, and targets never appeared at the other two, making them irrelevant. Analyses of the concurrently measured EEG signal were carried out on traditional narrowband alpha (8-14 Hz), as well as on two components resulting from the decomposition of this signal: periodic alpha; and the slope of the aperiodic 1/f-like component. Although data from right-left blocks replicated the familiar pattern of lateralized asymmetry in narrowband alpha power, with neither alpha signal could we find evidence for any difference in the time course at unattended versus irrelevant locations, an outcome consistent with the secondary-consequence interpretation of attention-related dynamics in the alpha band. Additionally, 1/f slope was lower at attended and unattended locations, relative to irrelevant, suggesting a tonic adjustment of physiological state.
Contextual control of conditioned pain tolerance and endogenous analgesic systems: Evidence for sex-based differences in endogenous opioid engagement
Authors: Trask Sydney , Mogil Jeffrey S. , Helmstetter Fred J. , Stucky Cheryl L. , Sadler Katelyn E.
Published: December 2021

The mechanisms underlying the transition from acute to chronic pain are unclear but may involve the persistence or strengthening of pain memories acquired in part through associative learning. Contextual cues, which comprise the surrounding environment where events occur, were recently described as a critical regulator of pain memory; both rodents and humans exhibit increased pain sensitivity in environments recently associated with a single painful experience. It is unknown, however, how repeated exposure to an acute painful unconditioned stimulus in a distinct context modifies pain sensitivity or the expectation of pain in that environment. To answer this question, we conditioned mice to associate distinct contexts with either repeated administration of a mild visceral pain stimulus (intraperitoneal injection of acetic acid) or vehicle injection over the course of three days. On the final day of experiments animals received either an acid injection or vehicle injection prior to being placed into both contexts. In this way, contextual control of pain sensitivity and pain expectation could be tested respectively. Both male and female mice developed context-dependent conditional pain tolerance, a phenomenon mediated by endogenous opioid signaling. However, when expecting the presentation of a painful stimulus in a given context, males exhibited conditional hypersensitivity whereas females exhibited endogenous opioid-mediated conditional analgesia. Successful determination of the brain circuits involved in this sexually dimorphic anticipatory response may allow for the manipulation of pain memories, which may contribute to the development of chronic pain states.
A chromosomal inversion may facilitate adaptation despite periodic gene flow in a freshwater fish
Authors: Thorstensen Matt J. , Euclide Peter T. , Jeffrey Jennifer D. , Shi Yue , Treberg Jason R. , Watkinson Douglas A. , Enders Eva C. , Larson Wesley A. , Kobayashi Yasuhiro , Jeffries Ken M.
Published: December 2021

Differences in genomic architecture between populations, such as chromosomal inversions, may play an important role in facilitating adaptation despite opportunities for gene flow. One system where chromosomal inversions may be important for eco-evolutionary dynamics are in freshwater fishes, which often live in heterogenous environments characterized by varying levels of connectivity and varying opportunities for gene flow. In the present study, reduced representation sequencing was used to study possible adaptation in n = 345 walleye (Sander vitreus) from three North American waterbodies: Cedar Bluff Reservoir (Kansas, USA), Lake Manitoba (Manitoba, Canada), and Lake Winnipeg (Manitoba, Canada). Haplotype and outlier-based tests revealed a putative chromosomal inversion that contained three expressed genes and was nearly fixed for alternate genotypes in each Canadian lake. These patterns exist despite several opportunities for gene flow between these proximate Canadian lakes, suggesting that the inversion may be important for facilitating adaptive divergence between the two lakes despite gene flow. Our study illuminates the importance of genomic architecture for facilitating local adaptation in freshwater fishes. Furthermore, our results provide additional evidence that inversions may facilitate local adaptation in many organisms that inhabit connected but heterogenous environments.
Phage resistance accompanies reduced fitness of uropathogenicE. coliin the urinary environment
Authors: Zulk Jacob J. , Clark Justin R. , Ottinger Samantha , Ballard Mallory B. , Mejia Marlyd E. , Mercado-Evans Vicki , Heckmann Emmaline R. , Sanchez Belkys C. , Trautner Barbara W. , Maresso Anthony W. , Patras Kathryn A.
Published: December 2021

Urinary tract infections (UTIs) are among the most common infections treated worldwide each year and are primarily caused by uropathogenicE. coli(UPEC). Rising rates of antibiotic resistance among uropathogens have spurred consideration of alternative strategies such as bacteriophage (phage) therapy; however, phage-bacterial interactions within the urinary environment are poorly defined. Here, we assess the activity of two phages, HP3 and ES17, against clinical UPEC isolates usingin vitroandin vivomodels of UTI. In both bacteriologic medium and pooled human urine, we identified phage resistance arising within the first 6-8 hours of coincubation. Whole genome sequencing revealed that UPEC resistant to HP3 and ES17 harbored mutations in genes involved in lipopolysaccharide (LPS) biosynthesis. These mutations coincided with severalin vitrophenotypes, including alterations to adherence to and invasion of human bladder epithelial HTB-9 cells, and increased biofilm formation. Interestingly, these phage-resistant UPEC demonstrated reduced growth in pooled human urine, which could be partially rescued by nutrient supplementation, and were more sensitive to several outer membrane targeting antibiotics than parental strains. Additionally, these phage-resistant UPEC were attenuated in a murine UTI model. In total, our findings suggest that while resistance to phages, such as LPS-targeted HP3 and ES17, may readily arise in the urinary environment, phage resistance is accompanied by fitness costs rendering UPEC more susceptible to host immunity or antibiotics.

IMPORTANCE

UTIs are one of the most common causes of outpatient antibiotic use, and rising antibiotic resistance threatens the ability to control these infections unless alternative treatments are developed. Bacteriophage (phage) therapy is gaining renewed interest, however, much like antibiotics, bacteria can readily become resistant to phage. For successful UTI treatment, we must predict how bacteria will evade killing by phage and identify the downstream consequences of phage-resistant bacterial infections. In our current study, we found that while phage-resistant mutant bacteria quickly emerged, these mutations left bacteria less capable of growing in human urine and colonizing the murine bladder. These results suggest that phage therapy poses a viable UTI treatment if phage resistance confers fitness costs for the uropathogen. These results have implications for developing cocktails of phage with multiple different bacterial targets, each of which is only evaded at the cost of bacterial fitness.
Historical biogeography of early diverging termite lineages (Isoptera: Teletisoptera)
Authors: Wang Menglin , Hellemans Simon , Šobotník Jan , Arora Jigyasa , Buček Aleš , Sillam-Dussès David , Clitheroe Crystal , Lu Tomer , Lo Nathan , Engel Michael S. , Roisin Yves , Evans Theodore A. , Bourguignon Thomas
Published: December 2021

Termites are social cockroaches distributed throughout warm temperate and tropical ecosystems. The ancestor of modern termites (crown-Isoptera) occurred during the earliest Cretaceous, approximately 140 million years ago, suggesting that both vicariance through continental drift and overseas dispersal may have shaped the distribution of early diverging termite lineages. We reconstruct the historical biogeography of three early diverging termite families – Stolotermitidae, Hodotermitidae, and Archotermopsidae – using the nuclear rRNA genes and mitochondrial genomes of 27 samples. Our analyses confirmed the monophyly of Stolotermitidae + Hodotermitidae + Archotermopsidae (clade Teletisoptera), with Stolotermitidae diverging from a monophyletic Hodotermitidae + Archotermopsidae approximately 100.3 Ma (94.3–110.4 Ma, 95% HPD), and with Archotermopsidae paraphyletic to a monophyletic Hodotermitidae. The Oriental Archotermopsis and the Nearctic Zootermopsis diverged 50.8 Ma (40.7–61.4 Ma, 95% HPD) before land connections between the Palearctic region and North America ceased to exist. The African Hodotermes + Microhodotermes diverged from Anacanthotermes, a genus found in Africa and Asia, 32.1 Ma (24.8–39.9 Ma, 95% HPD), and the most recent common ancestor of Anacanthotermes lived 10.7 Ma (7.3–14.3 Ma, 95% HPD), suggesting that Anacanthotermes dispersed to Asia using the land bridge connecting Africa and Eurasia ∼18–20 Ma. In contrast, the common ancestors of modern Porotermes and Stolotermes lived 20.2 Ma (15.7–25.1 Ma, 95% HPD) and 26.6 Ma (18.3–35.6 Ma, 95% HPD), respectively, indicating that the presence of these genera in South America, Africa, and Australia involved over-water dispersals. Our results suggest that early diverging termite lineages acquired their current distribution through a combination of over-water dispersals and dispersal via land bridges. We clarify the classification by resolving the paraphyly of Archotermopsidae, restricting the family to Archotermopsis and Zootermopsis, and elevating Hodotermopsinae (Hodotermopsis) as Hodotermopsidae (status novum).
Nucleophagy contributes to genome stability though TOP2cc and nucleolar components degradation
Authors: Muciño-Hernández Gabriel , Cárdenas Adán Oswaldo Guerrero , Merchant-Larios Horacio , Castro-Obregón Susana
Published: December 2021

The nuclear architecture of mammalian cells can be altered as a consequence of anomalous accumulation of nuclear proteins or genomic alterations. Most of the knowledge about nuclear dynamics comes from studies on cancerous cells. How normal, healthy cells maintain genome stability avoiding accumulation of nuclear damaged material is less understood. Here we describe that primary mouse embryonic fibroblasts develop a basal level of nuclear buds and micronuclei, which increase after Etoposide-induced DNA Double-Stranded Breaks. These nuclear buds and micronuclei co-localize with autophagic proteins BECN1 and LC3 and with acidic vesicles, suggesting their clearance by nucleophagy. Some of the nuclear alterations also contain autophagic proteins and Type II DNA Topoisomerases (TOP2A and TOP2B), or nucleolar protein Fibrillarin, implying they are also targets of nucleophagy. We propose that a basal nucleophagy contributes to genome and nuclear stability and also in response to DNA damage and nucleolar stress.
ABCA1 causes an asymmetric cholesterol distribution to regulate intracellular cholesterol homeostasis
Authors: Ogasawara Fumihiko , Ueda Kazumitsu
Published: December 2021

Cholesterol is a major and essential component of the mammalian cell plasma membrane (PM) and the loss of cholesterol homeostasis leads to various pathologies. Cellular cholesterol uptake and synthesis are regulated by a cholesterol sensor in the endoplasmic reticulum (ER). However, it remains unclear how the PM cholesterol level is sensed. Here we show that the sensing depends on ATP-binding cassette A1 (ABCA1) and Aster-A, which cooperatively maintain the asymmetric transbilayer cholesterol distribution in the PM. ABCA1 translocates (flops) cholesterol from the inner to the outer leaflet of the PM to maintain a low inner cholesterol level. When the inner cholesterol level exceeds a threshold, Aster-A is recruited to the PM-ER contact site to transfer cholesterol to the ER. These results show unknown synergy between ABCA1 and Aster-A in intracellular cholesterol homeostasis.
Comprehensive mapping of the alternative polyadenylation site usage and its dynamics at single cell resolution
Authors: Wang Junliang , Chen Wei , Hou Wenhong , Hong Ni , Zhong Hanbing , Ni Ting , Qi Yuanming , Jin Wenfei
Published: December 2021

Alternative polyadenylation (APA) plays an important role in post-transcriptional gene regulation such as transcript stability and translation efficiency. However, our knowledge about APA dynamics at single cell level is largely unexplored. Here we developed single cell polyadenylation sequencing (scPolyA-seq), a strand-specific approach for sequencing 3’ end of transcripts, to investigate the landscape of APA at single cell level. By analyzing several cell lines, we found many genes using multiple polyA sites in bulk data are prone to use only one polyA site in each single cell. Interestingly, cell cycle was significantly enriched in genes showing high variation of polyA site usages. We further identified 414 genes showing polyA site usage switch after cell synchronization. Genes showing cell cycle associated polyA site usage switch were grouped into 6 clusters, with cell phase specific functional categories enriched in each cluster. Furthermore, scPolyA-seq could facilitate study of APA in various biological processes.
Lactococcus lactis sb. cremoris orchestrates signal events in the gut epithelium via TLR2 to promote tissue restitution
Authors: Naudin Crystal R. , Owens Joshua A. , Askew Lauren C. , Khan Ramsha Nabihah , Scharer Christopher D. , Matthews Jason D. , Luo Liping , Kim Jiyoung , Reedy April R. , Barbian Maria E. , Jones Rheinallt M.
Published: December 2021

The use of beneficial bacteria to promote gastrointestinal heath is widely practiced, however, the mechanisms whereby many of these microbes elicit their beneficial effects remain elusive. Previously, we conducted a screen for the discovery of novel beneficial microbes and identified the potent cytoprotective effects of a strain of Lactococcus lactis subsp. cremoris. Here, we show that dietary supplementation with L. lactis subsp. cremoris induced transcript enrichment of a set of genes within the colon whose functions are associated with host cell and microbe interactions. Specifically, L. lactis subsp. cremoris induced the expression of tlr2, which we show was required for L. lactis subsp. cremoris to elicit its beneficial effects on the intestine. L. lactis subsp. cremoris did not confer beneficial effects in mice deficient in TLR-2, or deficient in its adaptor protein Myd88 in chronic gut injury models. In addition to cytoprotection, culture supernatant from L. lactis subsp. cremoris accelerated epithelial migration in a cultured epithelial cell scratch wound assay; and effect that was abrogated by a TLR-2 antagonist. Furthermore, L. lactis subsp. cremoris accelerated epithelial tissue restitution following the infliction of a colonic wound biopsy in a TLR-2 and Myd88-dependent manner. Within colonic wounds, L. lactis subsp. cremoris induced the activation of signaling pathways that function in tissue restitution following injury, including the ERK signaling pathway, and of focal adhesion complex (FAC) proteins. Together, these data demonstrate that L. lactis subsp. cremoris signals via the TLR2/MyD88-axis to confer cytoprotection and accelarated tissue restituion in the gut epithelium. These data point to evolving adaptations where beneficial gut microbes moduate innate immune signaling to excert positive influnces on host physiology.
Mutational switch-backs can accelerate evolution of Francisella to a combination of ciprofloxacin and doxycycline
Authors: Mehta Heer H. , Ibarra David , Marx Christopher J. , Miller Craig R. , Shamoo Yousif
Published: December 2021

Combination antimicrobial therapy has been considered a promising strategy to combat the evolution of antimicrobial resistance. Francisella tularensis is the causative agent of tularemia and in addition to being found in the nature, is recognized as a threat agent that requires vigilance. We investigated the evolutionary outcome of adapting the Live Vaccine Strain (LVS) of Francisella to two non-interacting drugs, ciprofloxacin and doxycycline, individually, sequentially, and in combination. Despite their individual efficacies and independence of mechanisms, evolution to the combination appeared to progress faster than evolution to the two drugs sequentially. We conducted a longitudinal mutational analysis of the populations evolving to the drug combination, genetically reconstructed the identified evolutionary pathway, and carried out biochemical validation. We discovered that, after the appearance of an initial weak generalist mutation (FupA/B), each successive mutation alternated between adaptation to one drug or the other. In combination, these mutations allowed the population to more efficiently ascend the fitness peak through a series of evolutionary switch-backs. Clonal interference, weak pleiotropy, and positive epistasis also contributed to combinatorial evolution. This finding suggests that, under some selection conditions, the use of non-interacting drug pairs as a treatment strategy may result in a more rapid ascent to multi-drug resistance and serves as a cautionary tale.

Author summary

The antimicrobial resistance crisis requires the use of novel treatment strategies to prevent or delay the emergence of resistance. Combinations of drugs offer one strategy to delay resistance, but the efficacy of such drug combinations depends on the evolutionary response of the organism. Using experimental evolution, we show that under some conditions, a potential drug combination does not delay the onset of resistance in bacteria responsible for causing tularemia, Francisella. In fact, they evolve resistance to the combination faster than when the two drugs are applied sequentially. This result is surprising and concerning: using this drug combination in a hospital setting could lead to simultaneous emergence of resistance to two antibiotics. Employing whole genome sequencing, we identified the molecular mechanism leading to evolution of resistance to the combination. The mechanism is similar to the switch-back route used by hikers while scaling steep mountains i.e., instead of simultaneously acquiring mutations conferring resistance to both drugs, the bacteria acquire mutations to each drug in alternating manner. Rather than scaling the steep mountain directly, the bacteria ascend the mountain by a series of evolutionary switch-backs to gain elevation and in doing so, they get to the top more efficiently.
Crystal structure and Hirshfeld surface analysis of 6-((E)-2-{4-[2-(4-chlorophenyl)-2-oxoethoxy]phenyl}ethenyl)-4,5-dihydropyridazin-3(2H)-one
Authors: Daoui Said , Muwafaq Israa , Çınar Emine Berrin , Abudunia Abdulmalik , Dege Necmi , Benchat Noureddine , Karrouchi Khalid
Published: December 2021

The pyridazine ring in the title compound, C20H17ClN2O3, adopts a screw-boat conformation. The whole molecule is flattened, the dihedral angles subtended by the least-squares plane of the central aromatic ring with those of the terminal benzene and pyridazine rings being 15.18 (19) and 11.23 (19)°, respectively. In the crystal, the molecules are linked by pairs of N—H...O bonds into centrosymmetric dimers and by C—H...π contacts into columns. The results of the Hirshfeld surface analysis show that the most prominent interactions are H...H, accounting for 36.5% of overall crystal packing, and H...O/O...H (18.6% contribution) contacts.
What users seek and share in online diabetes communities: examining similarities and differences in expressions and themes
Authors: Yao Zhizhen , Zhang Bin , Ni Zhenni , Ma Feicheng
Published: December 2021

Purpose

This paper aims to investigate user health information seeking and sharing patterns and content in an online diabetes community and explore the similarities and differences in the ways and themes they expressed.

Design/methodology/approach

Multiple methods are applied to analyze the expressions and themes that users seek and share based on large-scale text data in an online diabetes community. First, a text classifier using deep learning method is performed based on the expression category this study developed. Second, statistical and social network analyses are used to measure the popularity and compare differences between expressions. Third, topic modeling, manual coding and similarity analysis are used to mining topics and thematic similarity between seeking and sharing threads.

Findings

There are four different ways users seek and share in online health communities (OHCs) including informational seeking, situational seeking, objective information sharing and experiential information sharing. The results indicate that threads with self-disclosure could receive more replies and attract more users to contribute. This study also examines the 10 topics that were discussed for information seeking and 14 topics for information sharing. They shared three discussion themes: self-management, medication and symptoms. Information about symptoms can be largely matched between seeking and sharing threads while there is less overlap in self-management and medication categories.

Originality/value

Being different from previous studies that mainly describe one type of health information behavior, this paper analyzes user health information seeking and sharing behaviors in OHCs and investigates whether there is a correspondence or discrepancy between expressions and information users spontaneously seek and share in OHCs.
Open innovation and organizational ambidexterity
Authors: Hwang Bang-Ning , Lai Yi-Ping , Wang Chunhsien
Published: December 2021

Purpose

This study aims to examine the relationships among open innovation, organizational ambidexterity and firm performance. One important aspect of open innovation is that it enables a firm to develop its organizational ambidexterity capability and become more efficient in using this capability to improve its performance.

Design/methodology/approach

The authors introduce a moderated mediation theoretical framework to reveal the bridging role of organizational ambidexterity in the effect of open innovation on firm performance. The theoretical model is empirically validated using survey data from 215 high-tech firms.

Findings

The authors find that open innovation plays a moderating role in the relationship between organizational ambidexterity and firm performance. Furthermore, organizational ambidexterity plays a significant mediating role in the relationship between open innovation and firm performance, and open innovation has a nonlinear, inverse U-shaped moderation effect on the relationship between organizational ambidexterity and firm performance.

Research limitations/implications

This is one of the first studies to undertake a moderated mediation analysis by highlighting the mediating role of organizational ambidexterity and the moderating role of open innovation in influencing firm performance. The authors make a theoretical contribution to the field of open innovation and organizational behavior, and the authors provide concrete and feasible decision-making suggestions to decision makers adopting open innovation.

Practical implications

The empirical results can help high-tech firm managers ascertain the organizational ambidexterity practices that can be employed and determine the level of open innovation to enhance firm performance.

Originality/value

This research provides new insights into whether and how firms can grasp the benefits of organizational ambidexterity to undertake open innovation activities. The findings not only contribute to advancing the mediating effect of organizational ambidexterity but also verify the inverse U-shaped moderation of open innovation in the relationship between organizational ambidexterity and firm performance.
A conditional process model linking high-performance work systems, collective turnover, collectivist culture and organizational performance
Authors: Oh Jinuk , Kim Mijeong
Published: December 2021

Purpose

This study addresses three research questions: (1) do high-performance work systems (HPWS) enhance organizational performance by reducing collective turnover? (2) does a collectivist organizational culture moderate the link between collective turnover and organizational performance? (3) does collectivist organizational culture act as a boundary condition for the mediating effects of collective turnover in the link between HPWS and organizational performance?

Design/methodology/approach

A conditional process model linking HPWS, collective turnover, collectivist culture and organizational performance was developed and examined with longitudinal data collected at three different time points from 350 firms in South Korea.

Findings

The positive indirect effects of HPWS on organizational performance through collective turnover were significant. Regarding collectivist culture as a moderator, the negative relationship between collective turnover and organizational performance was stronger when the collectivist culture in the organization is high. In addition, the positive indirect effects of HPWS on organizational performance through collective turnover were also stronger when the collectivist culture in the organization is high.

Originality/value

This study provides a significant contribution to the areas of HPWS by reshaping the conceptual mechanisms in which HPWS enhance organizational performance. Further, it explores the significant role of collectivist culture as a moderator in the relationship between HPWS, collective turnover and organizational performance.
The impact of economic uncertainty, stock market uncertainty and monetary uncertainty on money demand in India
Authors: Khan Mohammad Azeem , Adil Masudul Hasan , Husain Shah
Published: December 2021

Purpose

The purpose of the paper is to address money demand instability and investigate the impact of economic uncertainty, stock market uncertainty and monetary uncertainty on money demand in India over the period 2003Q1–2019Q4.

Design/methodology/approach

The study checks the stationarity of the variables through standard unit root tests. Based on the mixed order of variables' integration, the authors adopt the autoregressive distributed lag (ARDL) model to confirm the cointegration and check the stability of the money demand function (MDF).

Findings

The findings confirm the presence of cointegration and reveal a well-specified MDF, which exhibits stable parameters. Besides the conventional variables, all forms of uncertainties emerge as the essential long-term determinants of money demand. Long-run findings show that people demand more money to avoid the future financial crunch amid high economic, monetary and stock market uncertainties.

Practical implications

The paper recommends, based on the findings, incorporating the monetary aggregates in the monetary policy framework as one of the essential information variables to control the fluctuation in the price level under the current flexible inflation targeting (FIT) regime.

Social implications

The findings also add to the knowledge of economic agents in terms of the overall response of individuals to changes in different forms of uncertainties, thereby helping to formulate their portfolios more diligently.

Originality/value

The current work is the first of its kind in the Indian context. The incorporation of uncertainty measures in the MDF adds to the existing knowledge on money demand.
Audiobook routines: identifying everyday reading by listening practices amongst young adults
Authors: Tattersall Wallin Elisa
Published: December 2021

Purpose

This article explores, identifies and conceptualises everyday audiobook reading practices amongst young adults.

Design/methodology/approach

Semi-structured interviews were conducted with ten Swedish audiobook users aged 18–19. The material was analysed using qualitative content analysis and focused on their audiobook use during an average weekday, as this was the time that they listened the most. The theoretical framework consists of theories on practice, time and everyday routine.

Findings

Five timespaces emerged when audiobook practices were most prevalent: morning routines, commuting routines, school routines, after school routines and bedtime routines. Within these timespaces, several practices could be identified and conceptualised. Three mobile practices were commute listening, exercise listening and chore listening while more stationary practices were homework listening, schoolwork listening and leisure listening. An unexpected finding was how audiobooks routinely were used to aid respondents’ wellbeing. This wellbeing listening was used to alleviate stress, loneliness and help listeners relax or fall asleep. Furthermore, respondents switch between Music, Audiobooks and Podcasts, which is conceptualised as MAP-switching.

Originality/value

There is a scarcity of research on audiobook use, and this paper contributes with new knowledge on audiobook reading practices, how audiobooks fit into everyday routine and provides concepts to aid further research on audiobook practices.
Family businesses in the tourism industry: a research agenda
Authors: Altın Hüseyin Ozan , Pirnar Ige , Eriş Engin Deniz , Gunlu Ebru
Published: December 2021

Purpose

The purpose of this study is to construct a comprehensive review on family businesses in the tourism industry since glocalization and small businesses comprise most of the industry.

Design/methodology/approach

This is a conceptual paper which utilizes qualitative research methods. Bibliometric analysis is applied to the selected 35 articles from specific databases which include not only the general tourism industry but also subsectors of airline, hospitality, restaurant, etc. Articles in this study fixate on the family businesses within the tourism industry.

Findings

In total, 35 articles are found with the keywords “family business and tourism”, “family business and hospitality and hotels”, “family business and restaurant” and “family business and airline”. Though the family business studies focus on hospitality, tourism and restaurants as F&B, there is a research gap in the subsectors like rent-a-car companies, travel agencies and tour operators and recreation facilities. Overall qualitative research design is preferred, but majority of the authors’ focus is on business development, profit, performance and succession. For further studies, quantitative analysis on research gap areas are recommended.

Research limitations/implications

The most general limitation is that only specific selected databases are used for the data gathering process such as double reviewed indexed journals published within Web of Science, Emerald, Elton B. Stephens Company (EBSCO) and Elsevier databases from the period of 1970s. Some other databases and some different periods may be considered as well as different keywords for other research. Secondly, few studies have analyzed quantitative data, since the specific nature of the family business dynamics require qualitative data. As a suggestion, not only qualitative analysis but also mixed methods may also be studied since the literature lacks the studies conducted with these methodologies.

Originality/value

The study contributes to the existing literature by providing a comprehensive review on hospitality and tourism family business management emphasizing the research gap on subsector application areas.
Can corporate governance mechanisms reduce earnings-management practices in Islamic banks?
Authors: Fitri Virasty , Siswantoro Dodik
Published: December 2021

Purpose

This study aims to provide empirical evidence on the role of corporate governance mechanisms in reducing earnings-management practices in Islamic banks in Asia.

Design/methodology/approach

This study used 28 Islamic banks in Asia, which were listed on the stock exchange from 2013–2017. The research method used quantitative regression with data on the characteristics of Islamic banks taken from the websites of each bank. This study used discretionary loan loss provision as a proxy for measuring earnings management.

Findings

The results show that only the audit committee size has a significantly negative effect on earnings management. An independent audit committee has a negative, but not significant, effect. The difference expectation signs cannot be interpreted further.

Research limitations/implications

Only a few components of corporate governance were tested in this study. Therefore, it is expected that future studies will include more components.

Practical implications

In general, the components of corporate governance that include the characteristics of the board of directors and the audit committee have a varied effect on reducing the earnings-management practices in Islamic banks, except audit committee size. In practice, audit committee size should have an important role in earning management reduces.

Originality/value

This may be the first paper that studies the effect of corporate governance on earnings management in Islamic banks in Asia.
AI led ethical digital transformation: framework, research and managerial implications
Authors: Saurabh Kumar , Arora Ridhi , Rani Neelam , Mishra Debasisha , Ramkumar M.
Published: December 2021

Purpose

Digital transformation (DT) leverages digital technologies to change current processes and introduce new processes in any organisation’s business model, customer/user experience and operational processes (DT pillars). Artificial intelligence (AI) plays a significant role in achieving DT. As DT is touching each sphere of humanity, AI led DT is raising many fundamental questions. These questions raise concerns for the systems deployed, how they should behave, what risks they carry, the monitoring and evaluation control we have in hand, etc. These issues call for the need to integrate ethics in AI led DT. The purpose of this study is to develop an “AI led ethical digital transformation framework”.

Design/methodology/approach

Based on the literature survey, various existing business ethics decision-making models were synthesised. The authors mapped essential characteristics such as intensity and the individual, organisational and opportunity factors of ethics models with the proposed AI led ethical DT. The DT framework is evaluated using a thematic analysis of 23 expert interviews with relevant AI ethics personas from industry and society. The qualitative data of the interviews and opinion data has been analysed using MAXQDA software.

Findings

The authors have explored how AI can drive the ethical DT framework and have identified the core constituents of developing an AI led ethical DT framework. Backed by established ethical theories, the paper presents how DT pillars are related and sequenced to ethical factors. This research provides the potential to examine theoretically sequenced ethical factors with practical DT pillars.

Originality/value

The study establishes deduced and induced ethical value codes based on thematic analysis to develop guidelines for the pursuit of ethical DT. The authors identify four unique induced themes, namely, corporate social responsibility, perceived value, standard benchmarking and learning willingness. The comprehensive findings of this research, supported by a robust theoretical background, have substantial implications for academic research and corporate applicability. The proposed AI led ethical DT framework is unique and can be used for integrated social, technological and economic ethical research.