bluuebunny/crossref_metadata_2025 huggingface dataset:
HLA-Glyco: A large-scale interrogation of the glycosylated immunopeptidome
Authors: Bedran Georges , Polasky Daniel A. , Hsiao Yi , Yu Fengchao , Veiga Leprevost Felipe da , Alfaro Javier A. , Cieslik Marcin , Nesvizhskii Alexey I.
Published: December 2022

MHC-associated peptides (MAPs) bearing post-translational modifications (PTMs) have raised intriguing questions regarding their attractiveness for targeted therapies. Here, we developed a novel computational glyco-immunopeptidomics workflow that integrates the ultrafast glycopeptide search of MSFragger with a glycopeptide-focused false discovery rate (FDR) control. We performed a harmonized analysis of 8 large-scale publicly available studies and found that glycosylated MAPs are predominantly presented by the MHC class II. We created HLA-Glyco, a resource containing over 3,400 human leukocyte antigen (HLA) class II N-glycopeptides from 1,049 distinct protein glycosylation sites. Our comprehensive resource reveals high levels of truncated glycans, conserved HLA-binding cores, and differences in glycosylation positional specificity between classical HLA class II allele groups. To support the nascent field of glyco-immunopeptidomics, we include the optimized workflow in the FragPipe suite and provide HLA-Glyco as a free web resource.
Detection of rare mutations, copy number variation, and DNA methylation in the same template DNA molecules
Authors: Wang Yuxuan , Douville Christopher , Cohen Joshua D. , Mattox Austin , Curtis Sam , Silliman Natalie , Popoli Maria , Ptak Janine , Dobbyn Lisa , Nehme Nadine , Dudley Jonathan C. , Summers Mahmoud , Zhang Ming , Bettegowda Chetan , Papadopoulos Nickolas , Kinzler Kenneth W. , Vogelstein Bert
Published: December 2022

The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics in the future.
Remote patient monitoring and digital therapeutics in heart failure: lessons from the Continuum pilot study
Authors: Marier-Tétrault Emmanuel , Bebawi Emmanuel , Béchard Stéphanie , Brouillard Philippe , Zuchinali Priccila , Remillard Emilie , Carrier Zoé , Jean-Charles Loyda , Nguyen John , Lehoux Pascale , Pomey Marie-Pascale , Ribeiro Paula A. B. , Tournoux François
Published: December 2022

Introduction

The increasing use of digital health solutions to monitor heart failure (HF) outpatients has been driven by the COVID-19 pandemic. An ideal technology should answer the specific needs of a public healthcare system: easy integration and proof of clinical benefit to justify investment in its long-term use. Through a consortium bringing together patients, physicians, industry, and hospital organizations, we developed a digital solution called “Continuum,” targeting patients with HF and other comorbidities.

Hypothesis

A digital health solution combining remote patient monitoring (RPM) and digital therapeutics (DTx) was developed to ensure a better follow-up of patients and to rapidly optimize their medication and subsequently avoid future severe adverse events.

Methods

A pilot intervention/control study with a three-month follow-up was conducted. Patients in the intervention group (remote patient monitoring group, RPM+) had a smartphone or tablet and entered in their mobile app their vital signs, weight, and HF symptoms daily. HF patients who either did not have a mobile device or the skills to use the app were enrolled in the control group (RPM-). The HealthCare Professionals (HCPs) used a web-based dashboard to follow the RPM+patients. They could access the results of a DTx solution to help them optimize the HF treatment according to Canadian guidelines.

Results

52 HF patients were enrolled in this study, 32 in the RPM+: 69±9y age, 75% male, ejection fraction 42 ± 14%. In the RPM-group, more patients had at least one hospitalization (all-cause) compared to the RPM+group (35% versus 6% respectively; p=0.008). Similarly, the number of patients with at least one HF hospitalization was more significant in the RPM+group compared to the RPM-(25% versus 6%, p=0.054). Finally, the intervention showed a medium effect on HF treatment optimization (w=0.26) and quality of life for the most compliant patients to the intervention (g=0.48).

Conclusion

The results of this pilot study demonstrated the feasibility of an intervention combining RPM and DTx solutions for HF patients. Preliminary results suggest promising impacts on quality of life, hospitalizations, and patients’ medication optimization. However, they need to be confirmed in a more extensive study.
Deprivation and Segregation in Ovarian cancer survival among African American Women: a mediated analysis
Authors: Lawson Andrew B. , Kim Joanne , Johnson Courtney , Hastert Theresa , Bandera Elisa V. , Alberg Anthony J. , Terry Paul , Akonde Maxwell , Mandle Hannah , Cote Michele L. , Bondy Melissa , Marks Jeffrey , Peres Lauren , Schildkraut Joellen , Peters Edward S.
Published: December 2022

Background

Deprivation and segregation indices are often examined as possible explanations for observed health disparities in population-based studies. In this study we assessed the role of recognized deprivation and segregation indices specifically as they affect survival in a cohort of self-identified Black women diagnosed with ovarian cancer who enrolled in the African American Cancer Epidemiology Study (AACES).

Methods

Mediation analysis was used to examine the direct and indirect effects between deprivation or segregation and overall survival, via a Bayesian structural equation model with Gibbs variable selection.

Results

The results suggest that high SES -related indices have an association with increased survival, ranging from 25%-56%. In contrast, ICE-race does not have a significant impact on overall survival. In many cases, the indirect effects have very wide credible intervals, consequently the total effect is not well estimated despite the estimation of the direct effect.

Conclusions

Our results show that black women living in higher SES neighborhoods are associated with increased survival with ovarian cancer, using area-level economic indices such as Yost or ICE-income. In addition, the KOLAK urbanization index has a similar impact, and the highlights importance of area-level deprivation and segregation as potentially modifiable social factors in ovarian cancer survival.
Increased Tryptophan, But Not Increased Glucose Metabolism, Predict Resistance of Pembrolizumab in Stage III/IV Melanoma
Authors: Oldan Jorge D. , Giglio Benjamin C. , Smith Eric , Zhao Weiling , Bouchard Deeanna M. , Ivanovic Marija , Lee Yueh Z. , Collichio Frances A. , Meyers Michael , Wallack Diana E. , Abernethy-Leinwand Amber , Long Patricia K. , Trembath Dimitri G. , Googe Paul B. , Kowalski Madeline H. , Ivanova Anastasia , Ezzell Jennifer , Feinberg Nana , Thomas Nancy E. , Wong Terence Z. , Ollila David W. , Li Zibo , Moschos Stergios J.
Published: December 2022

Clinical trials of combined IDO/PD1 blockade in metastatic melanoma (MM) failed to show additional clinical benefit compared to PD1-alone inhibition. We reasoned that a tryptophan-metabolizing pathway other than the kynurenine one is essential. We immunohistochemically stained tissues along the nevus-to-MM progression pathway for tryptophan-metabolizing enzymes (TMEs; TPH1, TPH2, TDO2, IDO1) and the tryptophan transporter, LAT1. We assessed tryptophan and glucose metabolism by performing baseline C11-labeled α-methyl tryptophan (C11-AMT) and fluorodeoxyglucose (FDG) PET imaging of tumor lesions in a prospective clinical trial of pembrolizumab in MM (clinicaltrials.gov,NCT03089606). We found higher protein expression of all TMEs and LAT1 in melanoma cells than tumor-infiltrating lymphocytes (TILs) within MM tumors (n=68). Melanoma cell-specific TPH1 and LAT1 expression are significantly anti-correlated with TIL presence in MM. High melanoma cell-specific LAT1 and low IDO1 expression were associated with worse overall survival (OS) in MM. Exploratory optimal cut-point survival analysis of pretreatment ‘high’ vs. ‘low’ C11-AMT SUVmaxof the hottest tumor lesion per patient revealed that the ‘low’ C11-AMT SUVmaxwas associated with longer progression-free and OS in our clinical trial (n=26). We saw no such trends with pretreatment FDG PET SUVmax. Treatment of melanoma cell lines with telotristat, a TPH1 inhibitor, increased IDO expression and kynurenine production in addition to suppression of serotonin production. High melanoma tryptophan metabolism is a poor predictor of pembrolizumab response and an adverse prognostic factor. Serotoninergic but not kynurenine pathway activation may be significant. Melanoma cells outcompete adjacent TILs, eventually depriving the latter of an essential amino acid.
The Australian academic STEMM workplace post-COVID: a picture of disarray
Authors: Christian Katherine , Larkins Jo-ann , Doran Michael R.
Published: December 2022

In 2019 we surveyed Australian early career researchers (ECRs) working in STEMM (science, technology, engineering, mathematics and medicine). ECRs almost unanimously declared a “love of research”, however, many reported frequent bullying and questionable research practices (QRPs), and that they intended to leave because of poor career stability. We replicated the survey in 2022 to determine the impact of the COVID-19 pandemic and sought more information on bullying and QRPs. Here, we compare data from 2019 (658 respondents) and 2022 (530 respondents), and detail poor professional and research conditions experienced by ECRs. Job satisfaction declined (62% versus 57%), workload concerns increased (48.6% versus 60.6%), more indicated “now is a poor time to commence a research career” (65% versus 76%) from 2019 to 2022, and roughly half reported experiencing bullying. Perhaps conditions could be tolerable if the ecosystem were yielding well-trained scientists and high-quality science. Unfortunately, there are signs of poor supervision and high rates of QRPs. ECRs detailed problems likely worthy of investigation, but few (22.4%) felt that their institute would act on a complaint. We conclude by suggesting strategies for ECR mentorship, training, and workforce considerations intended to maintain research excellence in Australia and improve ECR career stability.
Disruption offoscauses craniofacial anomalies in developing zebrafish
Authors: Maili Lorena , Tandon Bhavna , Yuan Qiuping , Menezes Simone , Hashmi S. Shahrukh , Letra Ariadne , Eisenhoffer George T. , Hecht Jacqueline T.
Published: December 2022

Craniofacial development is a complex and tightly regulated process and disruptions can lead to structural birth defects, the most common being nonsyndromic cleft lip and palate (NSCLP). Previously, we identifiedFOSas a candidate regulator of NSCLP through family-based association studies, yet its specific contributions to oral and palatal formation are poorly understood. This study investigated the role offosduring zebrafish craniofacial development through genetic disruption and knockdown approaches.Foswas expressed in the periderm, olfactory epithelium and other cell populations in the head. Genetic perturbation offosproduced an abnormal craniofacial phenotype with a hypoplastic oral cavity that showed significant changes in midface dimensions by quantitative facial morphometric analysis. Loss and knockdown offoscaused increased cell apoptosis in the head, followed by a significant reduction in cranial neural crest cells (CNCCs) populating the upper and lower jaws. These changes resulted in abnormalities of cartilage, bone and pharyngeal teeth formation. Periderm cells surrounding the oral cavity showed altered morphology and a subset of cells in the upper and lower lip showed disrupted Wnt/β-catenin activation, consistent with modified inductive interactions between mesenchymal and epithelial cells. Taken together, these findings demonstrate that perturbation offoshas detrimental effects on oral epithelial and CNCC-derived tissues suggesting that it plays a critical role in zebrafish craniofacial development and a potential role in NSCLP.

Summary statement

Perturbation offos, a candidate gene associated with nonsyndromic cleft lip and palate in humans, causes a distinctive orofacial phenotype in zebrafish as a result of abnormal development of craniofacial tissues. Disruption offosin the oral epithelial, cranial neural crest and Wnt responsive cell populations around the oral cavity causes anomalies that suggest a potential role in the etiology of NSCLP.
The Inherited Rate Matrix algorithm for phylogenetic model selection for non-stationary Markov processes
Authors: Tang Yurong , Kaehler Benjamin , Ying Hua , Huttley Gavin
Published: December 2022

In phylogenetic reconstruction, substitution models that assume nucleotide frequencies do not change through time are in very widespread use. DNA sequences can exhibit marked compositional difference. Such compositional heterogeneity implies sequence divergence has arisen from substitution processes that differ between the lineages. Accordingly, there has been considerable interest in exploring the non-stationary model class, which is capable of generating divergent sequence composition. These models are typically parameter rich and this richness is further compounded by the use of time-heterogeneous variants in order to capture compositional heterogeneity. This illuminates two barriers limiting the widespread application of the non-stationary model class: both the compute-time required to fit a model and the risk of model over-fitting increase with the number of parameters and the extent of time-heterogeneity. In this study, we address these issues with a novel model selection algorithm we term the Inherited Rate Matrix algorithm (hereafter IRM). This approach is based on the notion that a species inherits the substitution tendencies of its ancestor. We further present the non-stationary heterogeneous across lineages model (hereafter ns-HAL algorithm) which extends the HAL algorithm of Jayaswal et al. [2014] to the general nucleotide Markov process. The IRM algorithm substantially reduces the complexity of identifying a sufficient solution to the problem of time-heterogeneous substitution processes across lineages. We also address the issue of reducing the computing time with development of a constrained-optimisation approach for the IRM algorithm (fast-IRM). Our algorithms are implemented in Python 3. From a simulation study based on 2nd codon position genome sequences of yeast, we establish that IRM is significantly more accurate than both ns-HAL and heterogeneity in the substitution process across lineages (hereafter HAL) for close and dispersed sequences. IRM is up to 70× faster than ns-HAL while fast-IRM is around 140× faster. fast-IRM also showed a marked speed improvement over a C++ implementation of HAL. Our comparison of the accuracy of IRM with fast-IRM showed no difference with identical inferences made for all data sets. These two algorithms greatly improve the compute time for model selection of a non-stationary process, increasing the suite of problems to which this important substitution model class can be applied.
HexSDF are Required for Synthesis of a Novel Glycolipid that Mediates Daptomycin and Bacitracin Resistance inC. difficile
Authors: Pannullo Anthony G. , Guan Ziqiang , Goldfine Howard , Ellermeier Craig D.
Published: December 2022

Clostridioides difficileis a Gram-positive opportunistic pathogen that results in 250,000 infections, 12,000 deaths, and $1 billion in medical costs in the US each year. There has been recent interest in using a daptomycin analog, Surotomycin, to treatC. difficileinfections. Daptomycin interacts with both phosphatidylglycerol and Lipid II to disrupt the membrane and halt peptidoglycan synthesis.C. difficilehas an unusual lipid membrane composition as it has no phosphatidylserine or phosphatidylethanolamine, and ∼50% of its membrane is composed of glycolipids, including the uniqueC. difficilelipid aminohexosyl-hexosyldiradylglycerol (HNHDRG). We identified a two-component system (TCS) HexRK that is required forC. difficileresistance to daptomycin. Using RNAseq we found that HexRK regulates a three gene operon of unknown functionhexSDF. Based on bioinformatic predictions,hexSencodes a monogalactosyldiacylglycerol synthase,hexDencodes a polysaccharide deacetylase, andhexFencodes an MprF-like flippase. We find that deletion ofhexRKleads to a 4-fold decrease in daptomycin MIC, and that deletion ofhexSDFleads to an 8-16-fold decrease in daptomycin MIC. The ΔhexSDFmutant is also 4-fold less resistant to bacitracin but no other cell wall active antibiotics. Our data indicate that in the absence of HexSDF the phospholipid membrane composition is altered. In WTC. difficilethe unique glycolipid, HNHDRG makes up ∼17% of the lipids in the membrane. However, in a ΔhexSDFmutant, HNHDRG is completely absent. While it is unclear how HNHDRG contributes daptomycin resistance, the requirement for bacitracin resistance suggests it has a general role in cell membrane biogenesis.

Importance

Clostridioides difficileis a major cause of hospital acquired diarrhea and represents an urgent concern due to the prevalence of antibiotic resistance and the rate of recurrent infections. Little is understood aboutC. difficilemembrane lipids, but a unique glycolipid, HNHDRG, has been previously identified inC. difficileand, currently, has not been identified in other organisms. Here we show that HexSDF and HexRK are required for synthesis of HNHDRG, and that production of HNHDRG impacts resistance to daptomycin and bacitracin.
A widespread oscillatory network encodes an aggressive internal state
Authors: Grossman Yael S. , Talbot Austin , Gallagher Neil M. , Thomas Gwenaëlle E. , Fink Alexandra J. , Walder-Christensen Kathryn K. , Russo Scott J. , Carlson David E. , Dzirasa Kafui
Published: December 2022

Social aggression is an innate behavior that can aid an organism in securing access to resources[1], or it can impair group function and survival in behavioral pathology[2-4]. Since many brain regions contribute to multiple social behaviors[5-7], expanded knowledge of how the brain distinguishes between social states would enable the development of interventions that suppress aggression, while leaving other social behaviors intact. Here we show that a murine aggressive internal state is encoded by a widespread network. This network is organized by prominent and synchronized theta (4-11Hz) and beta (14-30Hz) oscillations that relay through the prefrontal cortex, and couples to widespread cellular firing. Strikingly, network activity during social isolation encodes the trait aggressiveness of mice, and causal cellular manipulations known to impact aggression can bidirectionally regulate the network’s activity. Finally, we use closed-loop stimulation of prefrontal cortex and causal mediation analysis to establish that the network is a mediator of aggressive behavior. Thus, we define a widespread network that encodes an aggressive internal state within and across mice.
13C ENDOR Spectroscopy-Guided MD Computations Reveals the Structure of the Enzyme-Substrate Complex of an Active, N-linked Glycosylated Lipoxygenase
Authors: Sharma Ajay , Whittington Chris , Jabed Mohammed , Hill S. Gage , Kostenko Anastasiia , Yu Tao , Li Pengfei , Hoffman Brian M. , Offenbacher Adam R.
Published: December 2022

Lipoxygenases (LOXs) are enzymes responsible for producing important cell signaling mediators and have been extensively studied for their potential clinical relevance as well as to advance our understanding of enzyme catalysis. The common inability to capture and characterize LOX-substrate complexes by Xray co-crystallography requires the development of alternative structural methods. We previously reported the integration of13C/1H electron nuclear double resonance (ENDOR) spectroscopy and molecular dynamics (MD) to visualize the complex structure of the paradigmatic LOX from soybean, SLO, with substrate linoleic acid (LA). However, this required substitution of the catalytic mononuclear, nonheme iron by the structurally faithful, yet inactive Mn2+ion as a spin-probe. Unlike canonical Fe-LOXs from plants and animals, LOXs from pathogenic fungi contain active mononuclear manganese metallocentres. Here, we report the ground-state active-site structure of the native, fully glycosylated fungal LOX fromM. oryzae, MoLOX complexed with LA obtained through the13C/1H ENDOR-guided MD approach. The Mn-oxygen-to-LA donor carbon distance (DAD) forMoLOX-LA, 3.4 ± 0.3 Å, matches the distance in the single representative X-ray co-structure of an animal 8R-LOX with its natural fatty acid substrate, and slightly elongated from that of the SLO-LA complex, 3.1 ± 0.2 Å, despite its ‘carboxylate-out’ substrate binding orientation versus ‘carboxylate-in’ for SLO. The results provide unique insight into the evolutionary divergence of the ground-state DAD in the LOX family, which influences the activation barrier for hydrogen tunneling, and give a structural basis for guiding development ofMoLOX inhibitors. The work highlights the robustness of ENDOR-guided MD approach to describe LOX-substrate structures that elude conventional X-ray techniques.
Activation of prefrontal cortex and striatal regions in rats after shifting between rules in a T-maze
Authors: Gao Hongying , Oberto Virginie , Biondi Ana , Sara Susan J. , Wiener Sidney I.
Published: December 2022

Prefrontal cortical and striatal areas have been identified by inactivation or lesion studies to be required for behavioral flexibility, including selecting and processing of different types of information. In order to identify these networks activated selectively during acquisition of new reward contingency rules, rats were trained to discriminate orientations of bars presented in pseudo-random sequence on two video monitors positioned behind the goal sites on a T maze with return arms. A second group already trained in the visual discrimination task learned to alternate left and right goal arm visits in the same maze while ignoring the visual cues still being presented. In each experimental group, once the rats reached criterion performance, the brains were prepared after a 90 minute delay, for later processing for c-fos immunohistochemistry. While both groups extinguished a prior strategy and acquired a new rule, they differed by the identity of the strategies, and previous learning experience. Among the 28 forebrain areas examined, there were significant increases in the relative density of c-fos immunoreactive cell bodies after learning the second rule in prefrontal cortex cingulate, prelimbic and infralimbic areas, in dorsomedial striatum and the core of nucleus accumbens, in ventral subiculum, and the central nucleus of the amygdala. These largely correspond to structures anatomically identified by previous inactivation studies. The data suggest that this dynamic network may underlie reward-based selection for action, a type of cognitive flexibility.
Characterization of BoHV-4 ORF45
Authors: Russo Luca , Capra Emanuele , Franceschi Valentina , Cavazzini Davide , Sala Roberto , Lazzari Barbara , Cavirani Sandro , Donofrio Gaetano
Published: December 2022

Bovine herpesvirus 4 (BoHV-4) is aGammaherpesvirusof the genusRhadinovirus, his natural host is the bovine whereas the African Buffalo the natural reservoir. Anyhow, BoHV-4 infection is not associated to a specific disease. Genome structure and genes are well conserved inGammaherpesvirus, andorf45 gene and its product, ORF45, is one of those. BoHV-4 ORF45 has been suggested to be a tegument protein, however, BoHV-4 ORF45 structure and function have not yet been experimentally characterized. In the present study, it is shown that BoHV-4 ORF45, despite its poor homology with other characterizedRhadinovirusORF45s, is structurally related to Kaposi’s sarcoma-associated herpesvirus (KSHV), is a phosphoprotein and localizes in the host cell nuclei. Through the generation of an ORF45-null mutant BoHV-4 and its pararevertant, it was possible to demonstrate that ORF45 is essential for BoHV-4 lytic replication and is associated to the viral particles, as for the other characterizedRhadinovirusORF45s. Finally, the impact of BoHV-4 ORF45 on cellular transcriptome was investigated, an aspect poorly explored or not at all for otherGammaherpesvirus. Many cellular transcriptional pathways were found to be alterate, mainly those involving p90 ribosomal S6 kinase (RSK) and signal-regulated kinase (ERK) complex (RSK/ERK), thus highlighting the authentic character of BoHV-4 ORF45 and paving the way to further investigations.
Rhythmic Entrainment Echoes in Auditory Perception
Authors: L’Hermite Sylvain , Zoefel Benedikt
Published: December 2022

Rhythmic entrainment echoes – rhythmic brain responses that outlast rhythmic stimulation – can evidence endogenous neural oscillations entrained by the stimulus rhythm. We here tested for such echoes in auditory perception. Participants detected a pure tone target, presented at a variable delay after another pure tone that was rhythmically modulated in amplitude. In four experiments involving 154 participants, we tested (1) which stimulus rate produces the strongest entrainment echo and (2) – inspired by audition’s tonotopical organisation and findings in non-human primates – whether these are organized according to sound frequency. We found strongest entrainment echoes after 6-Hz and 8-Hz stimulation, respectively. Best moments for target detection (in or in anti-phase with the preceding rhythm) depended on whether sound frequencies of entraining and target stimuli matched, in line with a tonotopical organisation. However, for the same experimental condition, best moments were not always consistent across experiments. We provide a speculative explanation for these differences that relies on the notion that neural entrainment and repetition-related adaptation might exercise competing, opposite influences on perception. Together, we find rhythmic echoes in auditory perception that seem more complex than those predicted from initial theories of neural entrainment.
Identification of a Female-produced Sex Attractant Pheromone of the Winter Firefly,Photinus corrusca
Authors: Lower Sarah E. , Pask Gregory M. , Arriola Kyle , Halloran Sean , Holmes Hannah , Halley Daphné C. , Zheng Yiyu , Collins Douglas B. , Millar Jocelyn G.
Published: December 2022

Firefly flashes are well-known visual signals used by these insects to find, identify, and choose mates. However, many firefly species have lost the ability to produce light as adults. These “unlighted” species generally lack developed adult light organs, are diurnal rather than nocturnal, and are believed to use volatile pheromones acting over a distance to locate mates. While cuticular hydrocarbons, which may function in mate recognition at close range, have been examined for a handful of the over 2000 extant firefly species, no volatile pheromone has ever been identified. In this study, using coupled gas chromatography - electroantennographic detection, we detected a single female-emitted compound that elicited antennal responses from wild-caught male winter fireflies,Photinus corrusca. The compound was identified as (1S)-exo-3-hydroxycamphor (hydroxycamphor). In field trials at two sites across the species’ eastern North American range, large numbers of maleP. corruscawere attracted to synthesized hydroxycamphor, verifying its function as a volatile sex attractant pheromone. Males spent more time in contact with lures treated with synthesized hydroxycamphor than those treated with solvent only in laboratory two-choice assays. Further, using single sensillum recordings, we characterized a pheromone-sensitive odorant receptor neuron in a specific olfactory sensillum on maleP. corruscaantennae and demonstrated its sensitivity to hydroxycamphor. Thus, this study has identified the first volatile pheromone and its corresponding sensory neuron for any firefly species, and provides a tool for monitoringP. corruscapopulations for conservation, and further inquiry into the chemical and cellular bases for sexual communication among fireflies.
Loss of allosteric regulation in α-isopropylmalate synthase identified as an antimicrobial resistance mechanism
Authors: Sullivan Jaryd R. , Courtine Christophe , Taylor Lorne , Solomon Ori , Behr Marcel A.
Published: December 2022

Despite our best efforts to discover new antimicrobials, bacteria have evolved mechanisms to become resistant. Resistance to antimicrobials can be attributed to innate, inducible, and acquired mechanisms.Mycobacterium abscessusis one of the most antimicrobial resistant bacteria and is known to cause chronic pulmonary infections within the cystic fibrosis community. Previously, we identified epetraborole as an inhibitor againstM. abscessuswithin vitroandin vivoactivities and that the efficacy of epetraborole could be improved with the combination of the non-proteinogenic amino acid norvaline. Norvaline demonstrated activity against theM. abscessusepetraborole resistant mutants thus, limiting resistance to epetraborole in wild type populations. Here we showM. abscessusmutants with resistance to epetraborole can acquire resistance to norvaline in a leucyl-tRNA synthetase (LeuRS) editing-independent manner. After showing that the membrane hydrophobicity and efflux activity are not linked to norvaline resistance, whole-genome sequencing identified a mutation in the allosteric regulatory domain of α-isopropylmalate synthase (α-IPMS). We found that mutants with the α-IPMSA555Vvariant incorporated less norvaline in the proteome and produced more leucine than the parental strain. Furthermore, we found that leucine can rescue growth inhibition from norvaline challenge in the parental strain. Our results demonstrate thatM. abscessuscan modulate its metabolism through mutations in an allosteric regulatory site to upregulate the biosynthesis of the natural LeuRS substrate and outcompete norvaline. These findings emphasize the antimicrobial resistant nature ofM. abscessusand describe a unique mechanism of substrate-inhibitor competition.

Significance Statement

Cystic fibrosis patients and individuals undergoing plastic surgery are at risk for acquiring chronic infections fromMycobacterium abscessus. Current antibiotics are not adequate and require increased drug discovery efforts to identify better treatments for these patients. The benzoxaborole, epetraborole has been shown by our group and others to be a promising candidate againstM. abscessusbut the emergence of resistance to epetraborole in a clinical trial for complicated urinary tract infections has hindered its development. Previously, we identified the combination of epetraborole and norvaline as a potential means to limit resistance against epetraborole. Our results here demonstrate thatM. abscessuscan acquire resistance to both epetraborole and norvaline. These results may help develop combination therapies to reduce the risk of resistance to benzoxaboroles and non-proteinogenic amino acids.
VPS35 and α-Synuclein Fail to Interact to Modulate Neurodegeneration in Rodent Models of Parkinson’s Disease
Authors: Chen Xi , Tsika Elpida , Levine Nathan , Moore Darren J.
Published: December 2022

Mutations in thevacuolar protein sorting 35 ortholog(VPS35) gene cause late-onset, autosomal dominant Parkinson’s disease (PD), with a single missense mutation (Asp620Asn, D620N) known to segregate with disease in families with PD. TheVPS35gene encodes a core component of the retromer complex, involved in the endosomal sorting and recycling of transmembrane cargo proteins.VPS35-linked PD is clinically indistinguishable from sporadic PD, although it is not yet known whetherVPS35-PD brains exhibit α-synuclein-positive brainstem Lewy pathology that is characteristic of sporadic cases. Prior studies have suggested a functional interaction between VPS35 and the PD-linked gene product α-synuclein in lower organisms, whereVPS35deletion enhances α-synuclein-induced toxicity. In mice, VPS35 overexpression is reported to rescue hippocampal neuronal loss in human α-synuclein transgenic mice, potentially suggesting a retromer deficiency in these mice. Here, we employ multiple well-established genetic rodent models to explore a functional or pathological interaction between VPS35 and α-synucleinin vivo. We find that endogenous α-synuclein is dispensable for nigrostriatal pathway dopaminergic neurodegeneration induced by the viral-mediated delivery of human D620N VPS35 in mice, suggesting that α-synuclein does not operate downstream of VPS35. We next evaluated retromer levels in affected brain regions from human A53T-α-synuclein transgenic mice, but find normal levels of the core subunits VPS35, VPS26 or VPS29. We further find that heterozygousVPS35deletion fails to alter the lethal neurodegenerative phenotype of these A53T-α-synuclein transgenic mice, suggesting the absence of retromer deficiency in this PD model. Finally, we explored the neuroprotective capacity of increasing VPS35 expression in a viral-based human wild-type α-synuclein rat model of PD. However, we find that the overexpression of wild-type VPS35 is not sufficient for protection against α-synuclein-induced nigral dopaminergic neurodegeneration, α-synuclein pathology and reactive gliosis. Collectively, our data suggest a limited interaction of VPS35 and α-synuclein in neurodegenerative models of PD, and do not provide support for their interaction within a common pathophysiological pathway.
Oxytocin signaling is necessary for synaptic maturation of adult-born neurons
Authors: Pekarek Brandon T. , Kochukov Mikhail , Lozzi Brittney , Wu Timothy , Hunt Patrick J. , Tepe Burak , Hanson Moss Elizabeth , Tantry Evelyne K. , Swanson Jessica L. , Dooling Sean W. , Patel Mayuri , Belfort Benjamin D.W. , Romero Juan M. , Bao Suyang , Hill Matthew C. , Arenkiel Benjamin R.
Published: December 2022

Neural circuit plasticity and sensory response dynamics depend on forming new synaptic connections. Despite recent advances toward understanding the consequences of circuit plasticity, the mechanisms driving circuit plasticity are unknown. Adult-born neurons within the olfactory bulb have proven to be a powerful model for studying circuit plasticity, providing a broad and accessible avenue into neuron development, migration, and circuit integration. We and others have shown that efficient adult-born neuron circuit integration hinges on presynaptic activity in the form of diverse signaling peptides. Here, we demonstrate a novel oxytocin-dependent mechanism of adult-born neuron synaptic maturation and circuit integration. We reveal spatial and temporal enrichment of oxytocin receptor expression within adult-born neurons in the murine olfactory bulb, with oxytocin receptor expression peaking during activity-dependent integration. Using viral labeling, confocal microscopy, and cell type-specific RNA-seq, we demonstrate that oxytocin receptor signaling promotes synaptic maturation of newly integrating adult-born neurons by regulating their morphological development and expression of mature synaptic AMPARs and other structural proteins.
Automatic generative design and optimization of hospital building layouts in consideration of public health emergency
Authors: Zhou Ying , Wang Yu , Li Chenshuang , Ding Lieyun , Wang Cong
Published: December 2022

Purpose

This study aimed to propose a performance-oriented approach of automatically generative design and optimization of hospital building layouts in consideration of public health emergency, which intended to conduct reasonable layout design of hospital building to meet different performance requirements for both high efficiency during normal periods and low risk in the pandemic.

Design/methodology/approach

The research design follows a sequential mixed methodology. First, key points and parameters of hospital building layout design (HBLD) are analyzed. Then, to meet the requirements of high efficiency and low risk, adjacent preference score and infection risk coefficient are constructed as constraints. On this basis, automatic generative design is conducted to generate building layout schemes. Finally, multi-objective deviation analysis is carried out to obtain the optimal scheme of hospital building layouts.

Findings

Automatic generative design of building layouts that integrates adjacent preferences and infection risks enables hospitals to achieve rapid transitions between normal (high efficiency) and pandemic (low risk) periods, which can effectively respond to public health emergencies. The proposed approach has been verified in an actual project, which can help systematically explore the solution for better decision-making.

Research limitations/implications

The form of building layouts is limited to rectangles, and future work can explore conducting irregular layouts into optimization for the framework of generative design.

Originality/value

The contribution of this paper is the developed approach that can quickly and effectively generate more hospital layout alternatives satisfying high operational efficiency and low infection risk by formulating space design rules, which is of great significance in response to public health emergency.
Collaborative online international learning between Spain and Mexico: a microlearning experience to enhance creativity in complexity
Authors: Romero-Rodríguez José-María , Ramirez-Montoya María Soledad , Glasserman-Morales Leonardo David , Ramos Navas-Parejo Magdalena
Published: December 2022

Purpose

The aim of this paper was to analyse the creative competence of students before and after a micro-learning experience carried out in a collaborative online international learning (COIL) environment between Spanish and Mexican university students in the field of education and entrepreneurship.

Design/methodology/approach

A single-group quasi-experimental design with pre-test and post-test measures was adopted. The composition of the group was natural and included a total of 57 students who participated in the COIL experience. The duration was three weeks, where students from both countries were linked together in the development of a micro-learning project. The creativity self-efficacy scale was used as a data collection instrument.

Findings

The micro-learning activities through COIL developed the creative competence of the participating students. In particular, the groups from both universities improved their scores on the creative competence in the post-test compared to the pre-test measure.

Research limitations/implications

The limitations of this study were linked to the sample loss of some cases, as some students did not complete the post-test measure. The main implication of the study was to demonstrate that COIL experiences are suitable for developing certain skills in students, such as creative competence or co-operative work.

Originality/value

COIL experiences break down the barriers of physical space and give students an active role, allowing them to fully develop competences and offering an intercultural perspective, which encourages open-mindedness and understanding of the world.
The gender diversity–performance linkage at the board of directors and the workforce levels: testing two competing curvilinear models
Authors: Campos-García Irene , Zúñiga-Vicente José Ángel
Published: December 2022

Purpose

The use of linear models has major limitations for accurately representing the true link between gender diversity and organizational performance. This study aims to explore two curvilinear models and tests which one – the U-shape or the inverted U-shape – best represents the gender diversity–performance link at two hierarchical levels: the board of directors and the workforce.

Design/methodology/approach

Both models are tested using data collected from a representative sample of Spanish educational organizations, which are dominated numerically by women, although women are still slightly underrepresented in managerial positions.

Findings

The results show the existence of an inverted U-shape and, therefore, the existence of a potential “optimal” level of gender diversity for both the board of directors and the workforce. While the highest performance by the board of directors is attained when the proportion of women and men is balanced in the workforce, the highest level of performance is attained when the proportion of women is greater.

Originality/value

There are hardly any studies simultaneously exploring the gender diversity–performance linkage at two hierarchical levels where the proportion of women/men is substantially different: the board of directors and the workforce. Thus, this study contributes to better know whether such relationship is dependent on the hierarchical position. It is important to know this because each level is related to different functions and tasks and shape a social status that can significantly influence performance.
NFC m-payment as a driver for customer loyalty towards retailers amongst Generation Z
Authors: Alt Mónika-Anetta , Agárdi Irma
Published: December 2022

Purpose

The diffusion of near-field communication (NFC) m-payment depends largely on retailers who are more motivated to provide NFC m-payment for the retailers' customers if NFC m-payment increases loyalty. Therefore, this paper investigates the relationship between customer acceptance of NFC m-payment and loyalty towards the retailer amongst Generation Z.

Design/methodology/approach

The NFC m-payment technology acceptance model was extended with loyalty intention towards the retailer. Therefore, an online survey was conducted amongst Generation Z that resulted in a sample of 310 respondents. The collected data were analysed by structural equation modelling (SEM).

Findings

Results proved that the customers' intention to use NFC m-payment contributes to a large extent to loyalty intention toward the retailer. Besides, usefulness, enjoyment, social influence and compatibility with lifestyle played a significant role in customer acceptance of NFC m-payment.

Research limitations/implications

This study's sample consists of Generation Z customers, and other generations should also be tested in future studies.

Practical implications

The intention to use NFC m-payment predict retail loyalty. Retailers should communicate m-payment availability as a new retail service to influence store patronage.

Originality/value

This study provides theoretical contributions to NFC m-payment acceptance and retail loyalty literature. First, this research extends the NFC m-payment technology acceptance model with a new behavioural outcome, loyalty intention towards retailers. Second, this research enriched retail loyalty literature by proving that NFC m-payment technology adoption drives customer loyalty towards retailers.
Tourism and COVID-19 in China: recovery and resilience strategies of main Chinese tourism cities
Authors: Yang Luqi , Li Xiaoni , Hernández-Lara Ana Beatriz
Published: December 2022

Purpose

The purpose of this study is to investigate the recovery and resilience tourism strategies and possible future development of four main Chinese tourism cities.

Design/methodology/approach

The authors collected data from the official accounts of tourism administrations of these cities, tourist attractions and opinions from media and newspapers in Sina Weibo platform. The authors adopted an inductive approach in observing relevant social media posts and applied content analysis to identify main China’s tourism prevention and recovery strategies.

Findings

During the mass pandemic infection period, top-down prevention and control measures were implemented by the Chinese central and local governments, with feasible and regional recovery policies and protocols being adapted according to local situations. Measures related to tourism industrial re-employment, improvement of international images and governmental financial supports to re-boost local tourism in Chinese cities were paid great attention. Digitalization, close-to-nature and cultural heritages became important factors in the future development of China’s tourism. Dark tourism, as a potential tourism recovery strategy, also obtained huge emergence, for the memory of people deceased in the pandemic and for the inheritance of national patriotism.

Originality/value

This study enriches the current literature in urban tourism recovery studies analyzing the specific case of Chinese tourism cities and fulfill some voids of previous research mostly focused on the first wave of the pandemic and the recovery strategies mainly of Western cities. It also provides valuable suggestions to tourism practitioners, destinations and urban cities in dealing with regional tourism recession and finding possible solutions for the scenario associated to the COVID-19 and other similar health crisis.
Beyond AI-powered context-aware services: the role of human–AI collaboration
Authors: Jiang Na , Liu Xiaohui , Liu Hefu , Lim Eric Tze Kuan , Tan Chee-Wee , Gu Jibao
Published: December 2022

Purpose

Artificial intelligence (AI) has gained significant momentum in recent years. Among AI-infused systems, one prominent application is context-aware systems. Although the fusion of AI and context awareness has given birth to personalized and timely AI-powered context-aware systems, several challenges still remain. Given the “black box” nature of AI, the authors propose that human–AI collaboration is essential for AI-powered context-aware services to eliminate uncertainty and evolve. To this end, this study aims to advance a research agenda for facilitators and outcomes of human–AI collaboration in AI-powered context-aware services.

Design/methodology/approach

Synthesizing the extant literature on AI and context awareness, the authors advance a theoretical framework that not only differentiates among the three phases of AI-powered context-aware services (i.e. context acquisition, context interpretation and context application) but also outlines plausible research directions for each stage.

Findings

The authors delve into the role of human–AI collaboration and derive future research questions from two directions, namely, the effects of AI-powered context-aware services design on human–AI collaboration and the impact of human–AI collaboration.

Originality/value

This study contributes to the extant literature by identifying knowledge gaps in human–AI collaboration for AI-powered context-aware services and putting forth research directions accordingly. In turn, their proposed framework yields actionable guidance for AI-powered context-aware service designers and practitioners.