bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms and Predictors of Acute Kidney Injury with Perioperative Rosuvastatin in Patients Undergoing Cardiac Surgery
Authors: Wijesurendra RS , Sardell R , Jayaram R , Samuel N , Chen Z , Staplin N , Collins R , Zheng Z , Haynes R , Hill M , Emberson J , Casadei B
Published: February 2023

Background

In patients undergoing cardiac surgery perioperative statin therapy has been associated with an unexpected increase in postoperative plasma creatinine. Here we investigated mechanisms and predictors of acute kidney injury (AKI) in 1922 patients enrolled in the Statin Therapy in Cardiac Surgery (STICS) randomized placebo-controlled trial of perioperative rosuvastatin (20 mg once daily).

Methods

AKI was defined according to international guidelines (KDIGO) using plasma creatinine, and also by cystatin C. Potentially mechanistically relevant plasma/serum biomarkers of muscle injury, inflammation, and kidney injury were investigated, including total creatine kinase (CK), growth differentiation factor 15 (GDF-15), interleukin-6 (IL-6), procalcitonin (PCT), placental growth factor (PLGF), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL).

Results

At 48 hours post-surgery, the incidence of AKI was greater in the rosuvastatin group than in the placebo group when defined by a rise in creatinine (24.7% vs 19.3%, p=0.005) or cystatin C (9.2% vs 5.1%, p<0.001); the majority of AKI was stage 1 in severity (87% when defined by creatinine, and 80% when defined by cystatin C). Compared with placebo, rosuvastatin led to higher postoperative serum levels of KIM-1 (278±5 pg/ml versus 259±5 pg/ml, P=0.01), and to more frequent elevations in CK to >10x and >40x the baseline level (30.9% versus 26.5%, p=0.032, and 2.1% versus 0.7%, p=0.016, respectively), whereas postoperative concentrations of GDF-15, IL-6, PCT, PLGF, and NGAL were similar between groups. In multivariable analyses, insulin treatment, baseline KIM-1, combined coronary artery bypass grafting (CABG) and aortic valve replacement (AVR) surgery, and allocation to rosuvastatin were all independently associated with AKI as defined by creatinine or cystatin C. Odds ratios for rosuvastatin compared to placebo for both creatinine- and cystatin C-defined AKI were not materially altered by further adjustment for post-randomization increases in CK.

Conclusions

Perioperative rosuvastatin initiation increased the absolute risk of AKI after cardiac surgery by 4-5%, whether defined by creatinine or cystatin C, and led to higher post-operative KIM-1, suggesting a deleterious effect on renal function, possibly mediated by proximal tubular injury. Insulin treatment, baseline KIM-1, combined CABG/AVR surgery, and allocation to rosuvastatin were all independently associated with AKI by any definition.
Age-specific severity of SARS-CoV-2 in February 2020 – June 2021 in the Netherlands
Authors: de Boer Pieter T. , van de Kassteele Jan , Vos Eric R.A. , van Asten Liselotte , Dongelmans Dave A. , van Gageldonk-Lafeber Arianne B. , Hartog Gerco den , Hofhuis Agnetha , van der Klis Fiona , de Lange Dylan W. , Stoeldraijer Lenny ,   the RIVM COVID-19 epidemiology and surveillance team, de Melker Hester E. , Geubbels Eveline , van den Hof Susan , Wallinga Jacco
Published: February 2023

Background

Severity of SARS-CoV-2 infection may vary over time. Here, we estimate age-specific risks of hospitalization, ICU admission and death given infection in the Netherlands from February 2020 to June 2021.

Methods

A nationwide longitudinal serology study was used to estimate numbers of infections in three epidemic periods (February 2020 – June 2020, July 2020 – February 2021, March 2021 – June 2021). We accounted for reinfections and, as vaccination started in January 2021, breakthrough infections among vaccinated persons. Severity estimates were inferred by combining numbers of infections with aligned numbers of hospitalizations and ICU admissions from a national hospital-based registry, and aligned numbers of deaths based on national excess all-cause mortality estimates.

Results

In each period there was a nearly consistent pattern of accelerating, almost exponential, increase in severity of infection with age. The rate of increase with age was highest for death and lowest for hospitalization. In the first period, the overall risk of hospitalization, ICU admission and death were 1.5% (95%-confidence interval [CI] 1.3-1.8%), 0.36% (95%-CI: 0.31-0.42%) and 1.2% (95%-CI: 1.0-1.4), respectively. The risk of hospitalization was higher in the following periods, while the risk of ICU admission remained stable. The risk of death decreased over time, with a substantial drop among ≥70-years-olds in February 2021 – June 2021.

Conclusion

The accelerating increase in severity of SARS-CoV-2 with age remained intact during the first three epidemic periods in the Netherlands. The substantial drop in risk of death among elderly in the third period coincided with the introduction of COVID-19 vaccination.
Assessing the cost-effectiveness of economic strengthening and parenting support for preventing violence against adolescents in South Africa: an economic modelling study using non-randomised data
Authors: Rudgard William E. , Obiesie Sopuruchukwu , Desmond Chris , Casale Marisa , Cluver Lucie
Published: February 2023

There is limited evidence around the cost-effectiveness of interventions to prevent violence against children in low- and middle-income countries. We developed a decision-analytic model to estimate the cost-effectiveness of 1) a community outreach intervention to link eligible households to anti-poverty cash grants, and 2) a group-based parenting support intervention, and 3) a group-based parenting support ‘plus’ linkage of eligible households to anti-poverty cash grants intervention for preventing adolescent violence victimisation in Mpumalanga province, South Africa.

The target population was families with an adolescent living below the national food poverty line. Modelled violence outcomes were emotional, physical, and sexual abuse. Intervention effectiveness was conditional on interventions’ effect on two evidence-based protective factors for adolescent violence: food security and caregiver supervision. Cost-effectiveness ratios were expressed per DALY averted and evaluated against a South Africa-specific willingness-to-pay threshold. We varied model parameters to consider routine service delivery versus trial-based costing, and population-average versus high prevalence of violence.

For routine service delivery costing, both community grant outreach and parenting support interventions were cost-effective at population-average prevalence (ACER=USD2,650, and ACER=USD2,830 per DALYs averted, respectively), and high prevalence of violence (ACER=USD1,330 and ACER=USD2,305 per DALYs averted, respectively). The incremental cost-effectiveness of adding grant linkage to parenting support was USD271 and USD177 at population-average and high prevalence of violence, respectively. For trial-based costing, none of the interventions were cost-effective at population-average prevalence of violence, and only community grant outreach was cost-effective at high prevalence of violence (ACER=USD2400 per DALY averted). Cost-effectiveness estimates are expected to be conservative based on our only modelling intervention effects on three violence outcomes via two protective factors.

Findings indicate that investments in community grant outreach, and parenting support interventions are likely to be cost-effective for preventing adolescent violence. Adding a grant linkage component to parenting support would enhance this approaches cost-effectiveness.
Protein Fitness Prediction is Impacted by the Interplay of Language Models, Ensemble Learning, and Sampling Methods
Authors: Mardikoraem Mehrsa , Woldring Daniel
Published: February 2023

Advances in machine learning (ML) and the availability of protein sequences via high-throughput sequencing techniques have transformed our ability to design novel diagnostic and therapeutic proteins. ML allows protein engineers to capture complex trends hidden within protein sequences that would otherwise be difficult to identify in the context of the immense and rugged protein fitness landscape. Despite this potential, there persists a need for guidance during the training and evaluation of ML methods over sequencing data. Two key challenges for training discriminative models and evaluating their performance include handling severely imbalanced datasets (e.g., few high-fitness proteins among an abundance of non-functional proteins) and selecting appropriate protein sequence representations. Here, we present a framework for applying ML over assay-labeled datasets to elucidate the capacity of sampling methods and protein representations to improve model performance in two different datasets with binding affinity and thermal stability prediction tasks. For protein sequence representations, we incorporate two widely used methods (One-Hot encoding, physiochemical encoding) and two language-based methods (next-token prediction, UniRep; masked-token prediction, ESM). Elaboration on performance is provided over protein fitness, length, data size, and sampling methods. In addition, an ensemble of representation methods is generated to discover the contribution of distinct representations to the final prediction score. Within the context of these datasets, the synthetic minority oversampling technique (SMOTE) outperformed undersampling while encoding sequences with One-Hot, UniRep, and ESM representations. In addition, ensemble learning increased the predictive performance of the affinity-based dataset by 4% compared to the best single encoding candidate (F1-score = 97%), while ESM alone was rigorous enough in stability prediction (F1-score = 92%).
A “Four Core Genotypes” rat model to distinguish mechanisms underlying sex-biased phenotypes and diseases
Authors: Arnold Arthur P. , Chen Xuqi , Grzybowski Michael N. , Ryan Janelle M. , Sengelaub Dale R. , Mohanroy Tara , Furlan V. Andree , Grisham William , Malloy Lynn , Takizawa Akiko , Wiese Carrie B. , Vergnes Laurent , Skaletsky Helen , Page David C. , Reue Karen , Harley Vincent R. , Dwinell Melinda R. , Geurts Aron M.
Published: February 2023

Background

We have generated a rat model similar to the Four Core Genotypes mouse model, allowing comparison of XX and XY rats with the same type of gonad. The model detects novel sex chromosome effects (XX vs. XY) that contribute to sex differences in any rat phenotype.

Methods

XY rats were produced with an autosomal transgene ofSry, the testis-determining factor gene, which were fathers of XX and XY progeny with testes. In other rats, CRISPR-Cas9 technology was used to remove Y chromosome factors that initiate testis differentiation, producing fertile XY gonadal females that have XX and XY progeny with ovaries. These groups can be compared to detect sex differences caused by sex chromosome complement (XX vs. XY) and/or by gonadal hormones (rats with testes vs. ovaries).

Results

We have measured numerous phenotypes to characterize this model, including gonadal histology, breeding performance, anogenital distance, levels of reproductive hormones, body and organ weights, and central nervous system sexual dimorphisms. Serum testosterone levels were comparable in adult XX and XY gonadal males. Numerous phenotypes previously found to be sexually differentiated by the action of gonadal hormones were found to be similar in XX and XY rats with the same type of gonad, suggesting that XX and XY rats with the same type of gonad have comparable levels of gonadal hormones at various stages of development.

Conclusion

The results establish a powerful new model to discriminate sex chromosome and gonadal hormone effects that cause sexual differences in rat physiology and disease.
CPA-Perturb-seq: Multiplexed single-cell characterization of alternative polyadenylation regulators
Authors: Kowalski Madeline H. , Wessels Hans-Hermann , Linder Johannes , Choudhary Saket , Hartman Austin , Hao Yuhan , Mascio Isabella , Dalgarno Carol , Kundaje Anshul , Satija Rahul
Published: February 2023

Most mammalian genes have multiple polyA sites, representing a substantial source of transcript diversity that is governed by the cleavage and polyadenylation (CPA) regulatory machinery. To better understand how these proteins govern polyA site choice we introduce CPA-Perturb-seq, a multiplexed perturbation screen dataset of 42 known CPA regulators with a 3’ scRNA-seq readout that enables transcriptome-wide inference of polyA site usage. We develop a statistical framework to specifically identify perturbation-dependent changes in intronic and tandem polyadenylation, and discover modules of co-regulated polyA sites exhibiting distinct functional properties. By training a multi-task deep neural network (APARENT-Perturb) on our dataset, we delineate acis-regulatory code that predicts responsiveness to perturbation and reveals interactions between distinct regulatory complexes. Finally, we leverage our framework to re-analyze published scRNA-seq datasets, identifying new regulators that affect the relative abundance of alternatively polyadenylated transcripts, and characterizing extensive cellular heterogeneity in 3’ UTR length amongst antibody-producing cells. Our work highlights the potential for multiplexed single-cell perturbation screens to further our understanding of post-transcriptional regulationin vitroandin vivo.
Exploring the consequences of redirecting an exocytic Rab onto endocytic vesicles
Authors: Li Xia , Liu Dongmei , Griffis Eric , Novick Peter
Published: February 2023

Bidirectional vesicular traffic links compartments along the exocytic and endocytic pathways. Rab GTPases have been implicated in specifying the direction of vesicular transport because anterograde vesicles are marked with a different Rab than retrograde vesicles. To explore this proposal, we sought to redirect an exocytic Rab, Sec4, onto endocytic vesicles by fusing the catalytic domain of the Sec4 GEF, Sec2, onto the CUE localization domain of Vps9, a GEF for the endocytic Rab, Ypt51. The Sec2GEF-GFP-CUE construct was found to localize to bright puncta predominantly near sites of polarized growth and this localization was strongly dependent upon the ability of the CUE domain to bind to the ubiquitin moieties added to the cytoplasmic tails of proteins destined for endocytic internalization. Sec4 and Sec4 effectors were recruited to these puncta with varying efficiency. The puncta appeared to consist of clusters of 80 nm vesicles and although the puncta are largely static, FRAP analysis suggests that traffic into and out of these clusters continues. Cells expressing Sec2GEF-GFP-CUE grew surprisingly well and secreted protein at near normal efficiency, implying that Golgi derived secretory vesicles were delivered to polarized sites of cell growth, where they tethered and fused with the plasma membrane despite the misdirection of Sec4 and its effectors. In total, the results suggest that while Rabs play a critical role in regulating vesicular transport, cells are remarkably tolerant of Rab misdirection.
Plasmid-mediated colistin resistance among human clinicalEnterobacteralesisolates: National surveillance in the Czech Republic
Authors: Zelendova Marketa , Papagiannitsis Costas C. , Sismova Petra , Medvecky Matej , Pomorska Katarina , Palkovicova Jana , Nesporova Kristina , Jakubu Vladislav , Jamborova Ivana , Zemlickova Helena , Dolejska Monika ,   Working Group for Monitoring of Antibiotic Resistance
Published: February 2023

The occurrence of colistin resistance has increased rapidly amongEnterobacteralesaround the world. We performed a national survey of plasmid-mediated colistin resistance in human clinical isolates by a retrospective analysis of samples from 2009-2017 and a prospective sampling in 2018-2020. The aim of this study was to identify and characterize isolates withmcrgenes from various regions of the Czech Republic using whole genome sequencing (WGS). Of all 1932 colistin-resistant isolates analyzed, 73 (3.8%) were positive formcrgenes. Most isolates carriedmcr-1(48/73) and were identified asEscherichia coli(n=44) andKlebsiella pneumoniae(n=4) of various sequence types (ST). Twenty-five isolates includingEnterobacterspp. (n=24) andCitrobacter freundii(n=1) carryingmcr-9gene were detected, three of them (Enterobacter kobeiST54) co-harbored themcr-4andmcr-9genes. Multi-drug resistance phenotype was a common feature ofmcrisolates and 14% (10/73) isolates also co-harboured clinically important beta-lactamases including 2 isolates with carbapenemases KPC-2 and OXA-48. Phylogenetic analysis ofE. coliST744, the dominant genotype in this study, with the global collection, showed Czech isolates belonged to two major clades, one containing isolates from Europe, while the second composed of isolates from diverse geographical areas. Themcr-1gene was carried by IncX4 (34/73, 47%), IncHI2/ST4 (6/73, 8%) and IncI2 (8/73, 11%) plasmid groups. Small plasmids belonging to the ColE10 group were associated withmcr-4in three isolates whilemcr-9was carried by IncHI2/ST1 plasmids (4/73, 5%) or the chromosome (18/73, 25%). We showed an overall low level of occurrence ofmcrgenes in colistin-resistant bacteria from human clinical samples in the Czech Republic.
Benchmarking Variational AutoEncoders on cancer transcriptomics data
Authors: Eltager Mostafa , Abdelaal Tamim , Charrout Mohammed , Mahfouz Ahmed , Reinders Marcel J.T. , Makrodimitris Stavros
Published: February 2023

Deep generative models, such as variational autoencoders (VAE), have gained increasing attention in computational biology due to their ability to capture complex data manifolds which subsequently can be used to achieve better performance in downstream tasks, such as cancer type prediction or subtyping of cancer. However, these models are difficult to train due to the large number of hyperparameters that need to be tuned. To get a better understanding of the importance of the different hyperparameters, we examined six different VAE models when trained on TCGA transcriptomics data and evaluated on the downstream task of cluster agreement with cancer subtypes. We studied the effect of the latent space dimensionality, learning rate, optimizer and initialization on the quality of subsequent clustering of the TCGA samples. We foundβ-TCVAE and DIP-VAE to have a good performance, on average, despite being more sensitive to hyperparameters selection. Based on these experiments, we derived recommendations for selecting the different hyperparameters settings. In addition, we examined whether the learned latent spaces capture biologically relevant information. Hereto, we correlated the different representations with various data characteristics such as age, days to metastasis, immune infiltration, and mutation signatures. We found that for all models the latent factors, in general, do not uniquely correlate with one of the data characteristics even for models specifically designed for disentanglement.
Impact of Peripheral Auditory Structure on the Development of Auditory-Language Network in Children with Profound Sensorineural Hearing Loss
Authors: Wang Yaoxuan , Jiang Mengda , Zhu Yuting , Xue Lu , Shu Wenying , Li Xiang , Chen Hongsai , Chu Yinghua , Song Yang , Tao Xiaofeng , Wang Zhaoyan , Wu Hao
Published: February 2023

Profound congenital sensorineural hearing loss (SNHL) prevents children from developing spoken language. Cochlear implantation and auditory brainstem implantation can provide hearing sensation, but language development outcomes can vary, particularly for patients with inner ear malformations and/or cochlear nerve deficiency (IEM&CND). Currently, the peripheral auditory structure is evaluated through visual inspection of clinical imaging, but this method is insufficient for surgical planning and prognosis. The central auditory pathway is also challenging to examine in vivo due to its delicate subcortical structures. Previous attempts to locate subcortical auditory nuclei using fMRI responses to sounds are not applicable to deaf patients. In this study, we developed a new pipeline for mapping the auditory pathway using structural and diffusional MRI. We used a fixel-based approach to investigate the structural development of the auditory-language network for profound SNHL children with normal peripheral structure and those with IEM&CND under six years old. Our findings indicate that the language pathway is more sensitive to peripheral auditory condition than the central auditory pathway, highlighting the importance of early intervention for profound SNHL children to provide timely speech inputs. We also propose a comprehensive pre-surgical evaluation extending from the cochlea to the auditory-language network, which has promising clinical potential.
Diet-induced rewiring of the Wnt gene regulatory network connects aberrant splicing to fatty liver and liver cancer in DIAMOND mice
Authors: López-Pérez Ana , Remeseiro Silvia , Hörnblad Andreas
Published: February 2023

Background & Aims

This study aimed to provide a comprehensive understanding of the regulatory and transcriptional landscape in liver tumours from DIAMOND mice, a mouse model that mimics human hepatocellular carcinoma (HCC) in the context of metabolic associated fatty liver disease (MAFLD).

Methods

RNA-sequencing and ChIP-sequencing were used to study the gene expression and regulatory changes in DIAMOND liver tumours. RNAin situhybridisation splice variant analysis was used to study β-catenin exon 3 exclusion in tumours at cellular resolution. Sequencing data on β-catenin exon 3 splicing in DIAMOND tumours was compared to data from human patients and cell lines.

Results

The study found an increase in Wnt/β-catenin-signalling accompanied by rewiring of the Wnt/β-catenin regulatory network in DIAMOND tumours. Changes include switching in the expression of the canonical TCF/LEF downstream effectors and associated chromatin remodelling. In addition, a large subset of DIAMOND tumours showed aberrant splicing of β-catenin, which generate an mRNA isoform that encodes an oncogenic protein. Similar splicing events were found in a fraction of human HCC and hepatoblastoma samples.

Conclusions

This study provides evidence that western diet induces aberrant genome-wide splicing in DIAMOND livers, and in particular of the β-catenin gene in a subset of DIAMOND liver tumours. This mechanism is distinct from previously reported activation of β-catenin in HCC and mouse models, since it is independent on mutations in the locus. Our data suggests that metabolic input modulates gene regulatory network responses to active Wnt-signalling, which will be an important consideration also in the human setting.

Lay summary

Sequencing data generated in this study highlights the effect of diet in modulating oncogenic gene expression and underscores an alternative mutation-independent mechanism leading to constitutive activation of β-catenin, a well-known driver of liver cancer.
Exploring the Knowledge of An Outstanding Protein to Protein Interaction Transformer
Authors: Yang Sen , Feng Dawei , Cheng Peng , Liu Yang , Wang Shengqi
Published: February 2023

Protein-to-protein interaction (PPI) prediction aims to predict whether two given proteins interact or not. Compared with traditional experimental methods of high cost and low efficiency, the current deep learning based approach makes it possible to discover massive potential PPIs from large-scale databases. However, deep PPI prediction models perform poorly on unseen species, as their proteins are not in the training set. Targetting on this issue, the paper first proposes PPITrans, a Transformer based PPI prediction model that exploits a language model pre-trained on proteins to conduct binary PPI prediction. To validate the effectiveness on unseen species, PPITrans is trained with Human PPIs and tested on PPIs of other species. Experimental results show that PPITrans significantly outperforms the previous state-of-the-art on various metrics, especially on PPIs of unseen species. For example, the AUPR improves 0.339 absolutely on Fly PPIs. Aiming to explore the knowledge learned by PPITrans from PPI data, this paper also designs a series of probes belonging to three categories. Their results reveal several interesting findings, like that although PPITrans cannot capture the spatial structure of proteins, it can obtain knowledge of PPI type and binding affinity, learning more than binary PPI.
The effect of hypoxia onDaphnia magnaperformance and its associated microbial and bacterioplankton community: a scope for Genotype x Microbial community interactions upon environmental stress ?
Authors: Coone Manon , Vanoverberghe Isabel , Houwenhuyse Shira , Verslype Chris , Decaestecker Ellen
Published: February 2023

The depletion of oxygen as a result of increased stratification and decreased oxygen solubility is one of the most significant chemical changes occurring in aquatic ecosystems as a result of global environmental change. Hence, more aquatic organisms will be exposed to hypoxic conditions over time. Deciphering the effects of hypoxia on strong ecological interactors in this ecosystem’s food web is critical for predicting how aquatic communities can respond to such an environmental disturbance. Here, (sub-)lethal effects of hypoxia and whether these are genotype specific inDaphnia, a keystone species of freshwater ecosystems, are studied. This is especially relevant upon studying genetic responses with respect to phenotypic switches (G x E interactions) upon environmental stress. Further, we investigated the effect of hypoxia on theDaphniamicrobial community to test if the microbiome plays a role in the phenotypic switch and tolerance to hypoxia. For this, twoDaphniagenotypes were exposed for two weeks to either hypoxia or normoxia and host performance was monitored together with changes in the host associated and free-living microbial community after this period. We found G x E interactions for some of the testedDaphniaperformance traits. The microbial community responded to hypoxia stress with responses in the bacterioplankton and in theDaphniaassociated microbial community with respect to species richness and community composition and structure. The latter response was different for the two genotypes suggesting that the microbiome plays an important role in G x E interactions with respect to hypoxia tolerance inDaphnia, but further testing (e.g. through microbiome transplants) is needed to confirm this.
Structural and functional classification of G-quadruplex families within the human genome
Authors: Neupane Aryan , Chariker Julia H. , Rouchka Eric C.
Published: February 2023

G quadruplexes are short secondary DNA structures located throughout genomic DNA and transcribed RNA. though G4 structures have been shown to formin vivo, no current search tools are known to exist to examine these structures based on previously identified G quadruplexes, much less filter them based on similar sequence, structure, and thermodynamic properties. We present a framework for clustering G quadruplex sequences into families using theCD-HIT, MeShClust and DNACLUSTmethods along with a combination ofStarcodeandBLAST. Utilizing this framework to filter and annotate clusters, 95 families of G quadruplex sequences were identified within the human genome. Profiles for each family were created using hidden Markov models to allow for identification of additional family members and generate homology probability scores. The thermodynamic folding energy properties, functional annotation of genes associated with the sequences, scores from different prediction algorithms and transcription factor binding and motif to the G4 region for the sequences within a family were used to annotate and compare the diversity within and across clusters. The resulting set of G quadruplex families can be used to further understand how different regions of the genome are regulated by factors targeting specific structures common to members of a specific cluster.
High Efficiency Rare Earth Element Biomining with Systems Biology Guided Engineering ofGluconobacter oxydans
Authors: Schmitz Alexa M. , Pian Brooke , Marecos Sabrina , Wu Mingming , Holycross Megan , Gazel Esteban , Reid Matthew C. , Barstow Buz
Published: February 2023

The global demand for critical rare earth elements (REE) is rising1with the increase in demand for sustainable energy technologies like wind turbines2,3, electric vehicles2,3, and high efficiency lighting4. Current processes for producing REE require high energy inputs and can produce disproportionate amounts of hazardous waste. Biological methods for REE production are a promising solution to this problem. In earlier work we identified the most important genetic mechanisms contributing to the REE-bioleaching capability ofGluconobacter oxydansB585. Here we have targeted two of these mechanisms to generate a high-efficiency bio-mining strain ofG. oxydans. Disruption of the phosphate-specific transport system through a clean deletion ofpstSconstitutively turns on the phosphate starvation response, yielding a much more acidic biolixiviant, and increasing bioleaching by up to 30%. Coupling knockout ofpstSwith the over-expression of themgdhmembrane-bound glucose dehydrogenase gene, results in up to 73% improvement of REE-bioleaching.
Labellable Phylogenetic Networks
Authors: Francis Andrew , Steel Mike
Published: February 2023

Abstract

Phylogenetic networks are mathematical representations of evolutionary history that are able to capture both tree-like evolutionary processes (speciations), and non-tree-like “reticulate” processes such as hybridization or horizontal gene transfer. The additional complexity that comes with this capacity, however, makes networks harder to infer from data, and more complicated to work with as mathematical objects.

In this paper we define a new, large class of phylogenetic networks, that we calllabellable, and show that they are in bijection with the set of “expanding covers” of finite sets. This correspondence is a generalisation of the encoding of phylogenetic forests by partitions of finite sets. Labellable networks can be characterised by a simple combinatorial condition, and we describe the relationship between this large class and other commonly studied classes. Furthermore, we show that all phylogenetic networks have a quotient network that is labellable.
Unified bursting strategies in ectopic and endogenouseven-skippedexpression patterns
Authors: Berrocal Augusto , Lammers Nicholas C , Garcia Hernan G , Eisen Michael B
Published: February 2023

Transcription often occurs in bursts as gene promoters switch stochastically between active and inactive states. Enhancers can dictate transcriptional activity in animal development through the modulation of burst frequency, duration, or amplitude. Previous studies observed that different enhancers can achieve a wide range of transcriptional outputs through the same strategies of bursting control. For example, despite responding to different transcription factors, alleven-skippedenhancers increase transcription by upregulating burst frequency and amplitude while burst duration remains largely constant. These shared bursting strategies suggest that a unified molecular mechanism constraints how enhancers modulate transcriptional output. Alternatively, different enhancers could have converged on the same bursting control strategy because of natural selection favoring one of these particular strategies. To distinguish between these two scenarios, we compared transcriptional bursting between endogenous and ectopic gene expression patterns. Because enhancers act under different regulatory inputs in ectopic patterns, dissimilar bursting control strategies between endogenous and ectopic patterns would suggest that enhancers adapted their bursting strategies to theirtrans-regulatory environment. Here, we generated ectopiceven-skippedtranscription patterns in fruit fly embryos and discovered that bursting strategies remain consistent in endogenous and ectopiceven-skippedexpression. These results provide evidence for a unified molecular mechanism shapingeven-skippedbursting strategies and serve as a starting point to uncover the realm of strategies employed by other enhancers.
Metabolic handoffs between multiple symbionts may benefit the deep-sea bathymodioline mussels
Authors: Zvi-Kedem Tal , Vintila Simina , Kleiner Manuel , Tchernov Dan , Rubin-Blum Maxim
Published: February 2023

Bathymodioline mussels rely on thiotrophic and methanotrophic chemosynthetic symbionts for nutrition, yet, secondary heterotrophic symbionts are often present and play an unknown role in the fitness of the organism. The bathymodiolineIdasmussels that thrive in gas seeps and on sunken wood in the Mediterranean Sea and the Atlantic Ocean, host at least six symbiont lineages that often co-occur, including the primary, chemosynthetic methane- and sulfur-oxidizing gammaproteobacteria, and the secondary Methylophagaceae, Nitrincolaceae and Flavobacteraceae symbionts, whose physiology and metabolism are obscure. Little is known about whether and how these symbionts interact or exchange metabolites. Here we curated metagenome-assembled genomes ofIdas modiolaeformissymbionts and used genomecentered metatranscriptomics and metaproteomics to assess key symbiont functions. The Methylophagaceae symbiont is a methylotrophic autotroph, as it encoded and expressed the ribulose monophosphate and Calvin-Benson-Bassham cycle enzymes, particularly RuBisCO. The Nitrincolaceae ASP10-02a symbiont likely fuels its metabolism with nitrogen-rich macromolecules and may provide the holobiont with vitamin B12. The FlavobacteriaceaeUrechidicolasymbionts likely degrade glycans and may remove NO. Our findings indicate that these flexible associations allow for expanding the range of substrates and environmental niches, via new metabolic functions and handoffs.
Genomic Analysis ofBlomia tropicalisIdentifies Novel Allergens for Component-Resolved Diagnosis of Mite Allergy
Authors: Xiong Qing , Liu Xiaoyu , Wan Angel Tsz-Yau , Malainual Nat , Xiao Xiaojun , Cao Hui , Tang Man-Fung , Ng Judy Kin-Wing , Shin Soo-Kyung , Sio Yang Yie , Wang Mingqiang , Sun Baoqing , Leung Ting-Fan , Chew Fook Tim , Tungtrongchitr Anchalee , Tsui Stephen Kwok-Wing
Published: February 2023

Background

Blomia(B.)tropicalis, as an important species of house dust mites (HDMs), plays a critical role in allergic diseases in tropical populations, but its allergen components are less investigated than those of other HDMs. Multiple omics methods have largely improved the identification of mite allergens. Here, we sought to identify a comprehensive allergen profile ofB. tropicalisand advance the allergen component-resolved diagnosis (CRD) of mite allergy.

Methods

Reference mite allergen sequences were searched in a high-quality genome ofB. tropicalis. Comparative analysis was performed for important allergen groups. ELISA was used to assess the allergenicities of recombinant proteins of specific allergens.

Results

A complete allergen profile ofB. tropicaliswas revealed, including thirty-seven allergen groups (up to Blo t 42). In-depth comparative analysis not only determined the homology of major allergen groups 5 and 21 but also shed light on the emergence and divergence of chitin-binding allergens. The specific Blo t 12 was identified to be a chitin-binding protein originating from the chitinase of allergen group 15. Immunoassays of recombinant proteins verified three novel allergens and the ELISA results suggested geographical differences in theB. tropicalissensitization rate.

Conclusions

The comprehensive allergen profile revealed inB. tropicalis, the comparative analysis of allergen groups and the immunoassay assessment of recombinant proteins largely expanded our knowledge toB. tropicalisallergens and could ultimately benefit the CRD of HDM allergy.
Exploring the black box of human resource and business strategy linkage: the effect of strategic fits on organizational performance
Authors: Boy Akdag Leyla , Ekmekci Özge Tayfur
Published: February 2023

Purpose

This study explores the effect of the strategic fit (tight-fit, minimal-fit and non-fit) between business strategies and human resource (HR) practices on perceived organizational performance (POP). It also investigates the moderating role of firm size on strategic fit–performance linkage.

Design/methodology/approach

The data were gathered via an online survey from HR managers of companies listed in “Fortune-500 Turkey, ISO-Top and Second-Top 500”. The form was distributed to 669 organizations, and 102 of them responded. The data were analyzed using one-way ANOVA and moderation analysis.

Findings

No statistically significant difference was found in organizational performance according to different strategic fit categories. The moderating effect of firm size was not significant. Yet, tight-fit and minimal-fit appear to be linked to higher organizational performance. The results reveal that business strategies aligned with HR practices could have a favorable impact on organizational performance.

Originality/value

The study differs from previous studies in terms of methodology, the conceptualization of strategic fit categories, the nature of the sample and non-Western origin.
Global retailers' CSR initiatives during COVID-19 crisis: a cross-cultural examination
Authors: Ahmad Wasim , Battisti Enrico , Akhtar Naeem , Ahmad Muhammad Ishfaq , Rehman Ramiz Ur
Published: February 2023

Purpose

This study develops a conceptual framework to examine (1) whether global retailers' CSR actions in the form of in-kind charitable contribution affect consumers' attribution of CSR to intrinsic motives, (2) whether consumers' attribution of CSR to intrinsic motives affects brand-self connection and (3) whether the cultural factors of self-transcendence and conservation moderate the relationship between consumers' attribution of CSR to intrinsic motives and brand-self connection.

Design/methodology/approach

Data are collected from two culturally diverse countries, the US and China, each of which managed the pandemic in different ways. Before hypothesis testing, the invariance of measures is established. To measure differences between the groups, a multi-group analysis is conducted.

Findings

Global retailers' in-kind charitable contribution is a significant drivers of consumers' attribution of CSR to intrinsic motives, and attribution of CSR to intrinsic motives has a positive effect on consumer brand-self connection. Both of the cultural values, self-transcendence and conservation, moderate the relationship between attribution of CSR to intrinsic motives and brand-self connection. Self-transcendence is a strong moderator in China, whereas conservation moderates strongly in the US. All of the relationships differ significantly between the groups (US versus China).

Originality/value

To the best of our knowledge, this is the first study to investigate empirically the role of in-kind charitable contribution in creating an attribution of CSR to intrinsic motives that eventually leads to strong brand-self connection in the COVID-19 context. The study provides novel insights into how consumer behavior differs across two significantly different cultures with regard to COVID-19-related CSR. The findings help international marketers manage uncertainties and crisis and to design their CSR-based marketing programs and develop positioning strategies across cultures.
Order matters: effect of use versus outreach order disclosure on persuasiveness of sponsored posts
Authors: Zhang Jin , Li Xinmai , Wu Banggang , Zhou Liying , Chen Xiang
Published: February 2023

Purpose

A critical step in influencer marketing is influencer outreach, where a brand reaches out to an influencer and forms a partnership. Yet little is known about how factors related to this process might influence the outcomes of sponsored posts. To address this gap, the authors investigated whether, how and when the order of influencers' product use and brand outreach (i.e. use/outreach order) affects post persuasiveness.

Design/methodology/approach

The authors conducted three experimental studies. Studies 1 and 2 examined the effect of disclosure type (use-first, outreach-later vs. outreach-first, use-later vs. no disclosure) on consumers' responses to the post. Study 3 investigated the moderating effects of compensation disclosure type.

Findings

The results revealed that when the influencer used the product before (vs. after) being contacted by the brand, consumers had more favorable attitudes about the product and greater purchase intention upon reading the sponsored posts; perceived information diagnosticity mediated this effect. However, this tendency was mitigated if the influencer disclosed the specific monetary payment from the brand.

Originality/value

This research advances understanding of sponsorship disclosure and provides a way to manage its impact on message persuasiveness.
More humility for leaders, less procrastination for employees: the roles of career calling and promotion focus
Authors: He Wei , Zhang Zheng , Guo Qian
Published: February 2023

Purpose

Based on the conservation of resources theory, the authors explore the relationship between humble leadership and employee procrastination by introducing career calling and promotion focus, and constructing a moderated mediation model aiming to reveal the influence of humble leadership on employee procrastination.

Design/methodology/approach

A total of 217 valid samples were obtained using a two-time point paired questionnaire. The proposed hypotheses were tested using hierarchical regression.

Findings

Hierarchical regression results indicated that humble leadership had a significant negative effect on employee procrastination. Career calling played a fully mediating role in humble leadership and employee procrastination. Promotion focus not only plays a positive moderating role between humble leadership and career calling but also moderates the mediating role of career calling.

Practical implications

Managers should pay attention to the cultivation of their own character of humility in the process of communicating with their subordinates, increase employees' career calling from various aspects to improve employees’ sense of meaning and value for their work and understand employees' situation for personalized management.

Originality/value

This study reveals for the first time the inhibitory effect of humble leadership on employee procrastination through the conservation of resources theory. This helps in expanding research on the antecedents of procrastination behavior and enriching research on the effects of implementing humble leadership. For this reason, the study contributes to the literature on humble leadership, employee procrastination and the conservation of resources theory.
Do financial constraints moderate the relationship between CEO compensation and firm performance: an emerging market evidence
Authors: Farooq Muhammad , Khan Muhammad Imran , Noor Amna
Published: February 2023

Purpose

The current study aims to investigate the impact of firm performance on chief executive officer (CEO) remuneration in the context of an emerging market, i.e. Pakistan. Further, the interactive effect of financial constraints is investigated in the pay–performance relationship.

Design/methodology/approach

The study's sample includes 173 non-financial firms listed on the Pakistan Stock Exchange. This study covers the years 2010–2019. The CEO compensation of the sample firms is measured in terms of salary and bonuses, perquisites and stock options paid to the CEO, whereas firm profitability is measured by return on assets, return on equity, Tobin's Q (Q) and earnings per share. The KZ Index measures the degree of financial constraint. The fixed effect model (FEM) and system GMM estimation techniques were used to conclude the study's findings. In addition, to test the robustness of the results, the authors computed the level of financial constraints using the WW Index.

Findings

The findings show that firm performance has a significant positive impact on CEO compensation in all profitability measures except Tobin's Q. Further financial constraints have a significant negative impact on CEO compensation. The interactive variables of FC with all profitability measures have a significant negative impact on CEO compensation.

Originality/value

This study examines the relationship between firm performance and CEO compensation. Furthermore, the current study expanded the analysis by incorporating the role of financial constraints in the pay–performance relationship, which has not previously been tested, particularly in the context of an emerging market.
Post-purchase behaviour triggers in branded mobile shopping apps
Authors: Dobre Costinel , Milovan Anca-Maria , Preda Gheorghe , Naghi Remus
Published: February 2023

Purpose

This study aims to integrate the perspectives offered by TAM and related models, respectively, the theory of values, to examine the impact of branded mobile shopping apps perceived value dimensions on continuance and recommendation intention.

Design/methodology/approach

A quantitative research was conducted online on a sample of 459 Romanian consumers to investigate how various facets of the perceived value of mobile shopping apps of some fashion brands influence continuance intention and the intention to recommend mobile apps. Sample selection implied a mixed non-probability method, convenience sampling and snowballing method, and the research hypotheses were tested using structural equation modelling (SEM) and path analysis.

Findings

This study validates significant positive relationships between perceived ubiquity, app incentive, respectively, epistemic value of branded mobile shopping apps and continuance intention, and between perceived hedonic value, social value, continuance intention and the intention to recommend branded mobile apps.

Originality/value

The research provides a deeper understanding of the influence played by the perceived value of mobile shopping apps on the consumer post-purchase behaviour and takes into consideration the mediating role of continuance intention for the perceived value and recommendation intention relationship.
Context-based learning for BIM: simulative role-playing games for strategic business implementations
Authors: Özener Ozan Önder
Published: February 2023

Purpose

This paper presents a set of instrumental case studies for the context-based learning of BIM in the milieu of knowledge-based practice in the AEC industry. The study aimed to examine students' actions and perspectives in a simulated learning environment for real-world BIM processes. The core intent was to provide an in-depth understanding of strategic and functional BIM implementation by synthesizing a suggestive pedagogical framework based on context-based learning approaches.

Design/methodology/approach

Derived from context-based approaches and experiential learning methods such as role-play, problem-based and active learning, the study involved a set of doctoral-level case studies. In a qualitative research study, these cases were devised and organized around industry-focused simulations on various levels of BIM implementation strategies.

Findings

Results from the case studies and the student responses suggest that the comprehensive evaluation of real-world BIM implementation simulations facilitates a solid understanding of the value of BIM. The participation of industry professionals catalyzes the development of strategic and functional BIM competencies.

Originality/value

The study proposes a well-structured and replicable BIM learning framework based on context-based learning approaches. The novel framework is adaptive and flexible for BIM education. It can provide students with the necessary skills, strategic vision and professional competencies for innovative practices in the 21st-century AEC Industry. The simulative learning settings, including the evaluation rubrics and connected instructional methods, can be implemented and further developed for similar education efforts.