bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the COVID-19 Pandemic on Emergency Adult Surgical Patients and Surgical Services
Authors: Winter Beatty Jasmine , Clarke Jonathan M. , Sounderajah Viknesh , Acharya Amish , Rabinowicz Simon , Martin Guy , Warren Leigh R. , Yalamanchili Seema , Scott Alasdair J. , Burgnon Elizabeth , Purkayastha Sanjay , Markar Sheraz , Kinross James M. ,   on behalf of the PANSURG-PREDICT Collaborative∗
Published: August 2021

Objectives:

The PREDICT study aimed to determine how the COVID-19 pandemic affected surgical services and surgical patients and to identify predictors of outcomes in this cohort.

Background:

High mortality rates were reported for surgical patients with COVID-19 in the early stages of the pandemic. However, the indirect impact of the pandemic on this cohort is not understood, and risk predictors are yet to be identified.

Methods:

PREDICT is an international longitudinal cohort study comprising surgical patients presenting to hospital between March and August 2020, conducted alongside a survey of staff redeployment and departmental restructuring. A subgroup analysis of 3176 adult emergency patients, recruited by 55 teams across 18 countries is presented.

Results:

Among adult emergency surgical patients, all-cause in-hospital mortality (IHM) was 3.6%, compared to 15.5% for those with COVID-19. However, only 14.1% received a COVID-19 test on admission in March, increasing to 76.5% by July.

Higher Clinical Frailty Scale scores (CFS >7 aOR 18.87), ASA grade above 2 (aOR 4.29), and COVID-19 infection (aOR 5.12) were independently associated with significantly increased IHM.

The peak months of the first wave were independently associated with significantly higher IHM (March aOR 4.34; April aOR 4.25; May aOR 3.97), compared to non-peak months.

During the study, UK operating theatre capacity decreased by a mean of 63.6% with a concomitant 27.3% reduction in surgical staffing.

Conclusion:

The first wave of the COVID-19 pandemic significantly impacted surgical patients, both directly through co-morbid infection and indirectly as shown by increasing mortality in peak months, irrespective of COVID-19 status.

Higher CFS scores and ASA grades strongly predict outcomes in surgical patients and are an important risk assessment tool during the pandemic.
The joint role of coevolutionary selection and network structure in shaping trait matching in mutualisms
Authors: Pedraza Fernando , Bascompte Jordi
Published: August 2021

Coevolution can sculpt remarkable trait similarity between mutualistic partners. Yet, it remains unclear which network topologies and selection regimes enhance trait matching. To address this, we simulate coevolution in topologically distinct networks under a gradient of mutualistic selection strength. We describe three main insights. First, trait matching is jointly influenced by the strength of mutualistic selection and the structural properties of the network where coevolution is unfolding. Second, the strength of mutualistic selection determines the network descriptors better correlated with higher trait matching. While network modularity enhances trait matching when coevolution is weak, network connectance does so when coevolution is strong. Third, the structural properties of networks outrank those of modules or species in determining the degree of trait matching. Our findings suggest networks can both enhance or constrain trait matching, depending on the strength of mutualistic selection.
A closer look at pupil diversity and evolution in frogs and toads
Authors: Cervino Nadia G. , Elias-Costa Agustín J. , Pereyra Martín O. , Faivovich Julián
Published: August 2021

The eyes of frogs and toads (Anura) are among their most fascinating features. Although several pupil shapes have been described, the diversity, evolution, and functional role of the pupil in anurans have received little attention. Studying photographs of more than 3200 species, we surveyed pupil diversity, described their morphological variation, tested correlation with adult habits and diel activity, and discuss major evolutionary patterns considering iris anatomy and visual ecology. Our results indicate that the pupil in anurans is a highly plastic structure, with seven main pupil shapes that evolved at least 116 times during the history of the group. We found no significant correlation between pupil shape, adult habits, and diel activity, with the exception of the circular pupil and aquatic habits. The vertical pupil arose at least in the most-recent common ancestor of Anura + Caudata, and this morphology is present in most early-diverging anuran clades. Subsequently, a horizontal pupil, a very uncommon shape in vertebrates, evolved in most neobatrachian frogs. This shape evolved into most other known pupil shapes, but it persisted in a large number of species with diverse life histories, habits, and diel activity patterns, demonstrating a remarkable functional and ecological versatility.
Bioenergetic consequences of sex-specific mitochondrial DNA evolution
Authors: Bettinazzi Stefano , Milani Liliana , Blier Pierre U. , Breton Sophie
Published: August 2021

Doubly uniparental inheritance (DUI) represents a notable exception to the general rule of strict maternal inheritance (SMI) of mitochondria in metazoans. This system entails the coexistence of two mitochondrial lineages (F- and M-type) transmitted separately through oocytes and sperm, thence providing an unprecedented opportunity for the mitochondrial genome to evolve adaptively for male functions. In this study, we explored the impact of a sex-specific mitochondrial evolution upon gamete bioenergetics of DUI and SMI bivalve species, comparing the activity of key enzymes of glycolysis, fermentation, fatty acid metabolism, tricarboxylic acid cycle, oxidative phosphorylation and antioxidant metabolism. Our findings suggest reorganized bioenergetic pathways in DUI gametes compared to SMI gametes. This generally results in a decreased enzymatic capacity in DUI sperm with respect to DUI oocytes, a limitation especially prominent at the terminus of the electron transport system. This bioenergetic remodelling fits a reproductive strategy that does not require high energy input and could potentially link with the preservation of the paternally transmitted mitochondrial genome in DUI species. Whether this phenotype may derive from positive or relaxed selection acting on DUI sperm is still uncertain.
The roles of antimicrobial resistance, phage diversity, isolation source and selection in shaping the genomic architecture of Bacillus anthracis
Authors: Bruce Spencer A. , Huang Yen-Hua , Kamath Pauline L. , van Heerden Henriette , Turner Wendy C.
Published: August 2021

Bacillus anthracis, the causative agent of anthrax disease, is a worldwide threat to livestock, wildlife and public health. While analyses of genetic data from across the globe have increased our understanding of this bacterium’s population genomic structure, the influence of selective pressures on this successful pathogen is not well understood. In this study, we investigate the effects of antimicrobial resistance, phage diversity, geography and isolation source in shaping population genomic structure. We also identify a suite of candidate genes potentially under selection, driving patterns of diversity across 356 globally extant

B. anthracis

genomes. We report ten antimicrobial resistance genes and 11 different prophage sequences, resulting in the first large-scale documentation of these genetic anomalies for this pathogen. Results of random forest classification suggest genomic structure may be driven by a combination of antimicrobial resistance, geography and isolation source, specific to the population cluster examined. We found strong evidence that a recombination event linked to a gene involved in protein synthesis may be responsible for phenotypic differences between comparatively disparate populations. We also offer a list of genes for further examination of

B. anthracis

evolution, based on high-impact single nucleotide polymorphisms (SNPs) and clustered mutations. The information presented here sheds new light on the factors driving genomic structure in this notorious pathogen and may act as a road map for future studies aimed at understanding functional differences in terms of

B. anthracis

biogeography, virulence and evolution.
Evaluation of ChIC-based data requires normalization that properly retains signal-to-noise ratios
Authors: Liu Bofeng , Chen Fengling , Xie Wei
Published: August 2021

Several chromatin immunocleavage-based (ChIC) methods using Tn5 transposase have been developed to profile histone modifications and transcription factors bindings1-5. A recent preprint by Wang et al. raised potential concerns that these methods are prone to open chromatin bias6. While the authors are appreciated for alerting the community for this issue, it has been previously described and discussed by Henikoff and colleagues in the original CUT&Tag paper3,7. However, as described for CUT&Tag3, the signal-to-noise ratio is essential for Tn5-based profiling methods and all antibody-based enrichment assays. Based on this notion, we would like to point out a major analysis issue in Wang et al. that caused a complete loss or dramatic reduction of enrichment at true targets for datasets generated by Tn5-based methods, which in turn artificially enhanced the relative enrichment of potential open chromatin bias. Such analysis issue is caused by distinct background normalizations used towards ChIP-based (chromatin immunoprecipitation) data and Tn5-based data in Wang et al. Only the normalization for Tn5-based data, but not ChIP-seq based data, yielded such effects. Distortion of such signal-to-noise ratio would consequently lead to misleading results.
Differences in working memory coding of biological motion attributed to oneself and others
Authors: Woźniak Mateusz , Schmidt Timo Torsten , Wu Yuan-hao , Blankenburg Felix , Hohwy Jakob
Published: August 2021

The question how the brain distinguishes between information about oneself and the rest of the world is of fundamental interest to both philosophy and neuroscience. This question can be approached empirically by investigating how associating stimuli with oneself leads to differences in neurocognitive processing. However, little is known about the brain network involved in forming such self-associations for, specifically, bodily stimuli. In this fMRI study, we sought to distinguish the neural substrates of representing a full-body movement as one’s movement and as someone else’s movement. Participants performed a delayed match-to-sample working memory task where a retained full-body movement (displayed using point-light walkers) was arbitrarily labelled as one’s own movement or as performed by someone else. By using arbitrary associations we aimed to address a limitation of previous studies, namely that our own movements are more familiar to us than movements of other people. A searchlight multivariate decoding analysis was used to test where information about types of movement and about self-association was coded. Movement specific activation patterns was found in a network of regions also involved in perceptual processing of movement stimuli, however not in early sensory regions. Information about whether a memorized movement was associated with the self or with another person was found to be coded by activity in the left middle frontal gyrus (MFG), left inferior frontal gyrus (IFG), bilateral supplementary motor area, and (at reduced threshold) in the left temporoparietal junction (TPJ). These areas are frequently reported as involved in action understanding (IFG, MFG) and domain-general self/other distinction (TPJ). Finally, in univariate analysis we found that selecting a self-associated movement for retention was related to increased activity in the ventral medial prefrontal cortex.
Clonal dynamics of haematopoiesis across the human lifespan
Authors: Mitchell Emily , Chapman Michael Spencer , Williams Nicholas , Dawson Kevin , Mende Nicole , Calderbank Emily F , Jung Hyunchul , Mitchell Thomas , Coorens Tim , Spencer David , Machado Heather , Lee-Six Henry , Davies Megan , Hayler Daniel , Fabre Margarete , Mahbubani Krishnaa , Abascal Fede , Cagan Alex , Vassiliou George , Baxter Joanna , Martincorena Inigo , Stratton Michael R , Kent David , Chatterjee Krishna , Parsy Kourosh Saeb , Green Anthony R , Nangalia Jyoti , Laurenti Elisa , Campbell Peter J
Published: August 2021

Age-related change in human haematopoiesis causes reduced regenerative capacity1, cytopenias2, immune dysfunction3 and increased risk of blood cancer. The cellular alterations that underpin the abruptness of this functional decline after the age of 70 years remain elusive. We sequenced 3579 genomes from single-cell-derived colonies of haematopoietic stem cell/multipotent progenitors (HSC/MPPs) across 10 haematologically normal subjects aged 0-81 years. HSC/MPPs accumulated 17 mutations/year after birth and lost 30bp/year of telomere length. Haematopoiesis in adults aged <65 was massively polyclonal, with high indices of clonal diversity and a stable population of 20,000–200,000 HSC/MPPs contributing evenly to blood production. In contrast, haematopoiesis in individuals aged >75 showed profoundly decreased clonal diversity. In each elderly subject, 30-60% of haematopoiesis was accounted for by 12-18 independent clones, each contributing 1-34% of blood production. Most clones had begun their expansion before age 40, but only 22% had known driver mutations. Genome-wide selection analysis estimated that 1/34 to 1/12 non-synonymous mutations were drivers, occurring at a constant rate throughout life, affecting a wider pool of genes than identified in blood cancers. Loss of Y chromosome conferred selective benefits on HSC/MPPs in males. Simulations from a simple model of haematopoiesis, with constant HSC population size and constant acquisition of driver mutations conferring moderate fitness benefits, entirely explained the abrupt change in clonal structure in the elderly. Rapidly decreasing clonal diversity is a universal feature of haematopoiesis in aged humans, underpinned by pervasive positive selection acting on many more genes than currently identified.
AMPing up the search: An in silico approach to identifying Antimicrobial Peptides (AMPs) with potential anti-biofilm activity
Authors: Mhade Shreeya , Panse Stutee , Tendulkar Gandhar , Awate Rohit , Kadam Snehal , Kaushik Karishma S
Published: August 2021

Antibiotic resistance is a public health threat, and the rise of multidrug-resistant bacteria, including those that form protective biofilms, further compounds this challenge. Antimicrobial peptides (AMPs) have been recognized for their anti-infective properties, including their ability to target processes important for biofilm formation. However, given the vast array of natural and synthetic AMPs, determining potential candidates for anti-biofilm testing is a significant challenge. In this study, we present an in silico approach, based on open-source tools, to identify AMPs with potential anti-biofilm activity. This approach is developed using the sortase-pilin machinery, important for adhesion and biofilm formation, of the multidrug-resistant, biofilm-forming pathogen C. striatum as the target. Using homology modeling, we modeled the structure of the C. striatum sortase C protein, resembling the semi-open lid conformation adopted during pilus biogenesis. Next, we developed a structural library of 5544 natural and synthetic AMPs from sequences in the DRAMP database. From this library, AMPs with known anti-Gram positive activity were filtered, and 100 select AMPs were evaluated for their ability to interact with the sortase C protein using in-silico molecular docking. Based on interacting residues and docking scores, we built a preference scale to categorize candidate AMPs in order of priority for future in vitro and in vivo biofilm studies. The considerations and challenges of our approach, and the resources developed, which includes a search-enabled repository of predicted AMP structures and protein-peptide interaction models relevant to biofilm studies (B-AMP), can be leveraged for similar investigations across other biofilm targets and biofilm-forming pathogens.
Hierarchical Bayesian models of transcriptional and translational regulation processes with delays
Authors: Cortez Mark Jayson , Hong Hyukpyo , Choi Boseung , Kim Jae Kyoung , Josić Krešimir
Published: August 2021

Motivation

Simultaneous recordings of gene network dynamics across large populations have revealed that cell characteristics vary considerably even in clonal lines. Inferring the variability of parameters that determine gene dynamics is key to understanding cellular behavior. However, this is complicated by the fact that the outcomes and effects of many reactions are not observable directly. Unobserved reactions can be replaced with time delays to reduce model dimensionality and simplify inference. However, the resulting models are non-Markovian, and require the development of new inference techniques.

Results

We propose a non-Markovian, hierarchical Bayesian inference framework for quantifying the variability of cellular processes within and across cells in a population. We illustrate our approach using a delayed birth-death process. In general, a distributed delay model, rather than a popular fixed delay model, is needed for inference, even if only mean reaction delays are of interest. Using in silico and experimental data we show that the proposed hierarchical framework is robust and leads to improved estimates compared to its non-hierarchical counterpart. We apply our method to data obtained using time-lapse microscopy and infer the parameters that describe the dynamics of protein production at the single cell and population level. The mean delays in protein production are larger than previously reported, have a coefficient of variation of around 0.2 across the population, and are not strongly correlated with protein production or growth rates.

Availability

Accompanying code in Python is available at https://github.com/mvcortez/Bayesian-Inference.

Contact

kresimir.josic@gmail.comkresimir.josic@gmail.com, jaekkim@kaist.ac.krjaekkim@kaist.ac.kr, cbskust@korea.ac.krcbskust@korea.ac.kr
SemiBin: Incorporating information from reference genomes with semi-supervised deep learning leads to better metagenomic assembled genomes (MAGs)
Authors: Pan Shaojun , Zhu Chengkai , Zhao Xing-Ming , Coelho Luis Pedro
Published: August 2021

Metagenomic binning is the step in building metagenome-assembled genomes (MAGs) when sequences predicted to originate from the same genome are automatically grouped together. The most widely-used methods for binning are reference-independent, operating de novo and allow the recovery of genomes from previously unsampled clades. However, they do not leverage the knowledge in existing databases. Here, we propose SemiBin, an open source tool that uses neural networks to implement a semi-supervised approach, i.e. SemiBin exploits the information in reference genomes, while retaining the capability of binning genomes that are outside the reference dataset. SemiBin outperforms existing state-of-the-art binning methods in simulated and real microbiome datasets across three different environments (human gut, dog gut, and marine microbiomes). SemiBin returns more high-quality bins with larger taxonomic diversity, including more distinct genera and species. SemiBin is available as open source software at https://github.com/BigDataBiology/SemiBin/.
Bias in miRNA enrichment analysis related to gene functional annotations
Authors: Zagganas Konstantinos , Vergoulis Thanasis , Georgakilas Georgios K. , Skiadopoulos Spiros , Dalamagas Theodore
Published: August 2021

Background

miRNA functional enrichment is a type of analysis that is used to predict which biological functions may be affected by a group of miRNAs or validate whether a list of dysregulated miRNAs are linked to a diseased state. The standard method for functional enrichment analysis uses the hypergeometric distribution to produce p-values, depicting the strength of the association between a group of miRNAs and a biological function. However, in 2015, it was shown that this approach suffers from a bias related to miRNA targets produced by target prediction algorithms and a new randomization test was proposed to alleviate this issue.

Results

We demonstrate the existence of another previously unreported underlying bias which affects gene annotation data sets; additionally, we show that the statistical measure used for the established randomization test is not sensitive enough to account for it. In this context, we show that the use of Jaccard coefficient (an alternative statistical measure) is able to alleviate the aforementioned issue.

Conclusions

In this paper, we illustrate the existence of a new bias affecting the miRNA functional enrichment analysis. This bias makes Fisher’s exact test unsuitable for miRNA functional enrichment analyses and there is also a need to adjust the established unbiased test accordingly. We propose the use of a modified version of the established test and in order to facilitate its use, we introduce a novel unbiased miRNA enrichment analysis tool that implements the proposed method. At the same time, by leveraging bit vectors, our tool guarantees fast and scalable execution.

Availability

All datasets used in the experiments throughout this paper are openly accessible on Zenodo (https://doi.org/10.5281/zenodo.5175819).
Epitranscriptomic reprogramming is required to prevent stress and damage from acetaminophen
Authors: Evke Sara , Melendez J. Andres , Lin Qishan , Begley Thomas J.
Published: August 2021

Epitranscriptomic marks, in the form of enzyme catalyzed RNA modifications, play important gene regulatory roles in response to environmental and physiological conditions. However, little is known with respect to how pharmaceuticals influence the epitranscriptome. Here we define how acetaminophen (APAP) induces epitranscriptomic reprogramming and how the writer Alkylation Repair Homolog 8 (Alkbh8) plays a key gene regulatory role in the response. Alkbh8 modifies tRNA selenocysteine (tRNASec) to translationally regulate the production of glutathione peroxidases (Gpx’s) and other selenoproteins, with Gpx enzymes known to play protective roles during APAP toxicity. We demonstrate that APAP increases toxicity and markers of damage, and decreases selenoprotein levels in Alkbh8 deficient mouse livers, when compared to wildtype. APAP also promotes large scale reprogramming of 31 RNA marks comprising the liver tRNA epitranscriptome including: 5-methoxycarbonylmethyluridine (mcm5U), isopentenyladenosine (i6A), pseudouridine (Ψ), and 1-methyladenosine (m1A) modifications linked to tRNASec and many others. Alkbh8 deficiency also leads to wide-spread epitranscriptomic dysregulation in response to APAP, demonstrating that a single writer defect can promote downstream changes to a large spectrum of RNA modifications. Our study highlights the importance of RNA modifications and translational responses to APAP, identifies writers as key modulators of stress responses in vivo and supports the idea that the epitranscriptome may play important roles in responses to pharmaceuticals.
Enhancer-promoter competition between homologous alleles leads to reduced transcription in early Drosophila embryos
Authors: Deng Hao , Lim Bomyi
Published: August 2021

The mechanism by which transcriptional machinery is recruited to enhancers and promoters to regulate gene expression is one of the most challenging and extensively studied questions in modern biology. Here, we ask if inter-allelic interactions between two homologous alleles can affect gene regulation. Using MS2- and PP7-based, allele-specific live imaging assay, we visualized de novo transcription of a reporter gene in hemizygous and homozygous Drosophila embryos. Surprisingly, each homozygous allele produced fewer RNAs than the hemizygous allele, suggesting the possibility of allelic competition in homozygotes. Moreover, the MS2-yellow reporter gene showed reduced transcriptional activity when a partial transcription unit (enhancer or promoter only) was in the homologous position. We propose that the transcriptional machinery that binds to both the enhancer and promoter region, such as RNA Pol II or preinitiation complexes, may be responsible for the allelic competition. To support this idea, we showed that the homologous alleles did not interfere with each other in earlier nuclear cycles when Pol II is in excess, while the degree of interference gradually increased in nuclear cycle 14. Such allelic competition was observed for endogenous snail as well. Our study provides new insights into the role of 3D inter-allelic interactions in gene regulation.
Tuning levels of low-complexity domain interactions to modulate endogenous oncogenic transcription
Authors: Chong Shasha , Graham Thomas G.W. , Dugast-Darzacq Claire , Dailey Gina M. , Darzacq Xavier , Tjian Robert
Published: August 2021

Gene activation by mammalian transcription factors (TFs) requires dynamic, multivalent, and selective interactions of their intrinsically disordered low-complexity domains (LCDs), but how such interactions mediate transcription remains unclear. It has been proposed that extensive LCD-LCD interactions culminating in liquid-liquid phase separation (LLPS) of TFs is the dominant mechanism underlying transactivation. Here, we investigated how tuning the amount and localization of LCD-LCD interactions in vivo affects transcription of endogenous human genes. Quantitative single-cell and single-molecule imaging reveals that the oncogenic TF EWS/FLI1 requires a finely tuned range of LCD-LCD interactions to efficiently activate target genes. Modest or more dramatic increases in LCD-LCD interactions toward putative LLPS repress EWS/FLI1-driven transcription in patient cells. Likewise, ectopically creating LCD-LCD interactions to sequester EWS/FLI1 into a bona fide LLPS compartment, the nucleolus, inhibits EWS/FLI1-driven transcription and oncogenic transformation. Our findings reveal fundamental principles underlying LCD-mediated transcription and suggest mislocalizing specific LCD-LCD interactions as a novel therapeutic strategy for targeting disease-causing TFs.
Stimulation of the Dorsal Root Ganglion using an Injectrode®
Authors: Dalrymple Ashley N , Ting Jordyn E , Bose Rohit , Trevathan James K , Nieuwoudt Stephan , Lempka Scott F , Franke Manfred , Ludwig Kip A , Shoffstall Andrew J , Fisher Lee E , Weber Douglas J
Published: August 2021

Objective

The goal of this work was to compare afferent fiber recruitment by dorsal root ganglion (DRG) stimulation using an injectable polymer electrode (Injectrode®) and a more traditional cylindrical metal electrode.

Approach

We exposed the L6 and L7 DRG in four cats via a partial laminectomy or burr hole. We stimulated the DRG using an Injectrode or a stainless steel electrode using biphasic pulses at three different pulse widths (80, 150, 300 μs) and pulse amplitudes spanning the range used for clinical DRG stimulation. We recorded antidromic evoked compound action potentials (ECAPs) in the sciatic, tibial, and common peroneal nerves using nerve cuffs. We calculated the conduction velocity of the ECAPs and determined the charge-thresholds and recruitment rates for ECAPs from Aα, Aβ, and Aδ fibers. We also performed electrochemical impedance spectroscopy measurements for both electrode types.

Main Results

The ECAP thresholds for the Injectrode did not differ from the stainless steel electrode across all primary afferents (Aα, Aβ, Aδ) and pulse widths; charge-thresholds increased with wider pulse widths. Thresholds for generating ECAPs from Aβ fibers were 100.0 ± 32.3 nC using the stainless steel electrode, and 90.9 ± 42.9 nC using the Injectrode. The ECAP thresholds from the Injectrode were consistent over several hours of stimulation. The rate of recruitment was similar between the Injectrodes and stainless steel electrode and decreased with wider pulse widths.

Significance

The Injectrode can effectively excite primary afferents when used for DRG stimulation within the range of parameters used for clinical DRG stimulation. The Injectrode can be implanted through minimally invasive techniques while achieving similar neural activation to conventional electrodes, making it an excellent candidate for future DRG stimulation and neuroprosthetic applications.
Metagenomic Discovery of CRISPR-Associated Transposons
Authors: Rybarski James R. , Hu Kuang , Hill Alexis M. , Wilke Claus O. , Finkelstein Ilya J.
Published: August 2021

CRISPR-associated transposons (CASTs) co-opt Cas genes for RNA-guided transposition. CASTs are exceedingly rare in genomic databases; recent surveys have reported Tn7-like transposons that co-opt Type I-F, I-B, and V-K CRISPR effectors. Here, we expand the diversity of reported CAST systems via a bioinformatic search of metagenomic databases. We discover new architectures for all known CASTs, including novel arrangements of the Cascade effectors, new self-targeting modalities, and minimal V-K systems. We also describe new families of CASTs that have co-opted the Type I-C and Type IV CRISPR-Cas systems. Our search for non-Tn7 CASTs identifies putative candidates that co-opt Cas12a for horizontal gene transfer. These new systems shed light on how CRISPR systems have co-evolved with transposases and expand the programmable gene editing toolkit.
Batch experiments demonstrating a two-stage bacterial process coupling methanotrophic and heterotrophic bacteria for 1-alkene production from methane
Authors: Khanongnuch Ramita , Mangayil Rahul , Santala Ville , Hestnes Anne Grethe , Svenning Mette Marianne , Rissanen Antti J
Published: August 2021

Methane (CH4) is a sustainable carbon feedstock source for aerobic CH4-oxidizing bacteria (methanotrophs) to produce value-added chemicals. Under substrate-limited (e.g., CH4, oxygen and nitrogen) conditions, CH4 oxidation results in the production of various short-chain organic acids and platform chemicals. These CH4-derived products could be broadened by utilizing them as a feedstock for heterotrophic bacteria. As a proof of concept, a two-stage system for CH4 abatement and 1-alkene production was developed in this study. Types I and II methanotrophs, i.e., Methylobacter tundripaludum SV96 and Methylocystis rosea SV97, respectively, were investigated in batch tests under different CH4 and air supplementation schemes. CH4 oxidation under either microaerobic or aerobic conditions induced the production of formate, acetate, succinate, and malate in M. tundripaludum SV96, accounting for 4.8-7.0% of consumed CH4-carbon while M. rosea SV97 produced the same compounds except for malate, and with lower efficiency than M. tundripaludum SV96, accounting for 0.7-1.8% of consumed CH4-carbon For the first time, the organic acids-rich spent media of methanotrophs were successfully used for 1-alkene production using engineered Acinetobacter baylyi ADP1 ‘tesA-undA cells. The highest yield of 1-undecene was obtained from spent medium of M. tundripaludum SV96 at 68.9 ± 11.6 μmol mol Csubstrate−1.
CNN based Heuristic Function for A* Pathfinding Algorithm: Using Spatial Vector Data to Reconstruct Smooth and Natural Looking Plant Roots
Authors: Yasrab Robail , Pound Michael P
Published: August 2021

In this work we propose an extension to recent methods for the reconstruction of root architectures in 2-dimensions. Recent methods for the automatic root analysis have proposed deep learned segmentation of root images followed by path finding such as Dijkstra’s algorithm to reconstruct root topology. These approaches assume that roots are separate, and that a shortest path within the image foreground represents a reliable reconstruction of the underlying root structure. This approach is prone to error where roots grow in close proximity, with path finding algorithms prone to taking “short cuts” and overlapping much of the root material. Here we extend these methods to also consider root angle, allowing a more informed shortest path search that disambiguates roots growing close together. We adapt a CNN architecture to also predict the angle of root material at each foreground position, and utilise this additional information within shortest path searchers to improve root reconstruction. Our results show an improved ability to separate clustered roots.
Complexity of brain dynamics as a correlate of consciousness in anaesthetized monkeys
Authors: Fuentes Nicolas , García Alexis , Guevara Ramón , Orofino Roberto , Mateos Diego M.
Published: August 2021

The use of anaesthesia is a fundamental tool in the investigation of consciousness. Anesthesia procedures allow to investigate different states of consciousness from sedation to deep anesthesia within controlled scenarios. In this study we use information quantifiers to measure the complexity of electrocorticogram recordings in monkeys. We apply these metrics to compare different stages of general anesthesia for evaluating consciousness in several anesthesia protocols. We find that the complexity of brain activity can be used as a correlate of consciousness. For two of the anaesthetics used, propofol and medetomidine, we find that the anaesthetised state is accompanied by a reduction in the complexity of brain activity. On the other hand we observe that use of ketamine produces an increase in complexity measurements. We relate this observation with increase activity within certain brain regions associated with the ketamine used doses. Our measurements indicate that complexity of brain activity is a good indicator for a general evaluation of different levels of consciousness awareness, both in anesthetized and non anesthetizes states.
Treatment of a metabolic liver disease by in vivo prime editing in mice
Authors: Böck Desirée , Rothgangl Tanja , Villiger Lukas , Schmidheini Lukas , Mathis Nicholas , Ioannidi Eleonora , Kreutzer Susanne , Kontarakis Zacharias , Rimann Nicole , Grisch-Chan Hiu Man , Thöny Beat , Schwank Gerald
Published: August 2021

Prime editing is a highly versatile CRISPR-based genome editing technology with the potential to correct the vast majority of pathogenic mutations (1). However, correction of a disease phenotype in vivo in somatic tissues has not been demonstrated thus far. Here, we establish proof-of-concept for in vivo prime editing and repair the metabolic liver disease phenylketonuria (PKU) in mice. We first developed a size-reduced SpCas9 prime editor (PE) lacking the RNaseH domain of the reverse transcriptase (PE2ΔRnH), and a linker- and NLS-optimized intein-split PE construct (PE2 p.1153) for delivery by adeno-associated virus (AAV) vectors. Systemic dual AAV-mediated delivery of this variant into the liver of neonatal mice enabled installation of a transversion mutation at the Dnmt1 locus with an average efficiency of 15%, and delivery of unsplit PE2ΔRnH using human adenoviral vector 5 (AdV5) further increased editing rates to 58%. PE2ΔRnH-encoding AdV5 was also used to correct the disease-causing mutation of the phenylalanine hydroxylase (Pah)enu2 allele in phenylketonuria (PKU) mice with an average efficiency of 8% (up to 17.3%), leading to therapeutic reduction of blood phenylalanine (L-Phe) levels. Our study demonstrates in vivo prime editing in the liver with high precision and editing rates sufficient to treat a number of metabolic liver diseases, emphasizing the potential of prime editing for future therapeutic applications.

One Sentence Summary

In vivo prime editing corrects phenylketonuria in mice.
Polyoxometalate-like structure of new potassium triphenylsiloxides: [K6(OSiPh3)6(C3H7OH)(H2O)]·2C6H5CH3 and [K6(OSiPh3)6(H2O)2]
Authors: Wytrych Patrycja , Utko Józef , Lis Tadeusz , John Łukasz
Published: August 2021

The synthesis and structural characterization of two new potassium triphenylsiloxides, namely, aqua(propan-2-ol)hexakis(triphenylsilanolato)hexapotassium toluene disolvate, [K6(C18H15OSi)6(C3H8O)(H2O)]·2C7H8, and diaquahexakis(triphenylsilanolato)hexapotassium, [K6(C18H15OSi)6(H2O)2], are reported. Both compounds crystallize in the triclinic space group P-1. The structure in each case resembles an alkali metal polyoxometalate-like structure, in which electrostatic interactions are observed in the metal–oxygen core. Furthermore, both compounds also resemble a reverse micelles-like architecture, in which the hydrophilic core is enclosed in a hydrophobic shell. The cores of the complexes are flanked by hydrophobic aromatic rings derived from Ph3SiO− anions, where intramolecular π-interactions between the aromatic rings and potassium cations stabilize the cores of the crystals. Moreover, in both structures, the presence of hydrogen bonds is observed; until now, no crystal structures have been described containing K atoms and triphenylsiloxide molecules in which the presence of hydrogen bonds was confirmed. Thus, these coordination entities could be considered as attractive reagents for further synthetic protocols towards heterometallic complexes.
Crystal structures and hydrogen-bonding analysis of a series of benzamide complexes of zinc(II) chloride
Authors: Tinapple Elizabeth , Farrar Sam , Johnston Dean H.
Published: August 2021

Ionic co-crystals are co-crystals between organic molecules and inorganic salt coformers. Co-crystals of pharmaceuticals are of interest to help control polymorph formation and potentially improve stability and other physical properties. We describe the preparation, crystal structures, and hydrogen bonding of five different 2:1 benzamide or toluamide/zinc(II) chloride co-crystal salts, namely, bis(benzamide-κO)dichloridozinc(II), [ZnCl2(C7H7NO)2], dichloridobis(2-methylbenzamide-κO)zinc(II), [ZnCl2(C8H9NO)2], dichloridobis(3-methylbenzamide-κO)zinc(II), [ZnCl2(C8H9NO)2], dichloridobis(4-methylbenzamide-κO)zinc(II), [ZnCl2(C8H9NO)2], and dichloridobis(4-hydroxybenzamide-κO)zinc(II), [ZnCl2(C7H7NO2)2]. All of the complexes contain hydrogen bonds between the amide N—H group and the amide carbonyl oxygen atoms or the chlorine atoms, forming extended networks.
Synthesis, crystal structure and magnetic properties of poly[[diaqua{μ6-2-[bis(carboxylatomethyl)amino]terephthalato}dicobalt(II)] 1.6-hydrate]
Authors: Ma Jie , Zhang Wen-Zhi , Liu Yong , Yi Wen-Tao
Published: August 2021

The asymmetric unit of the polymeric title compound {[Co2(C12H7NO8)(H2O)2]·1.6H2O}
n
comprises two CoII ions, which are coordinated by fully deprotonated 2-aminodiacetic terephthalic acid (adtp4–) and terminal water molecules in distorted octahedral N1O5 and O6 coordination environments. The title compound features tetranuclear CoII units bridged by κ
3
O:O:O′- and κ
3
O:O,O′-carboxylate groups, which are joined into ribbons via syn–anti carboxylate bridges. The parallel adtp4– ligands with an alternately reversed arrangement further link adjacent CoII ribbons into (010) layers, which are assembled into a three-dimensional supramolecular network via intermolecular hydrogen bonds. The disordered water solvent molecules are situated in channels parallel to [100]. Magnetic measurements and analyses reveal that the title compound displays antiferromagnetic behaviour. The purity of the title compound was characterized by X-ray powder diffraction.
Multi-source information fusion based on factor graph in autonomous underwater vehicles navigation systems
Authors: Ma Xiaoshuang , Liu Xixiang , Li Chen-Long , Che Shuangliang
Published: August 2021

Purpose

This paper aims to present a multi-source information fusion algorithm based on factor graph for autonomous underwater vehicles (AUVs) navigation and positioning to address the asynchronous and heterogeneous problem of multiple sensors.

Design/methodology/approach

The factor graph is formulated by joint probability distribution function (pdf) random variables. All available measurements are processed into an optimal navigation solution by the message passing algorithm in the factor graph model. To further aid high-rate navigation solutions, the equivalent inertial measurement unit (IMU) factor is introduced to replace several consecutive IMU measurements in the factor graph model.

Findings

The proposed factor graph was demonstrated both in a simulated and vehicle environment using IMU, Doppler Velocity Log, terrain-aided navigation, magnetic compass pilot and depth meter sensors. Simulation results showed that the proposed factor graph processes all available measurements into the considerably improved navigation performance, computational efficiency and complexity compared with the un-simplified factor graph and the federal Kalman filtering methods. Semi-physical experiment results also verified the robustness and effectiveness.

Originality/value

The proposed factor graph scheme supported a plug and play capability to easily fuse asynchronous heterogeneous measurements information in AUV navigation systems.
Understanding corporate culture and business performance from a Confucian perspective
Authors: Tian Vane-Ing , Tang Felix , Tse Alan C.B.
Published: August 2021

Purpose

This paper aims to develop a culturally sensitive model based on the Chinese Confucian philosophy and normative ethics, which emphasizes the wholehearted social responsibility of a Junzi (a noble man). Analogous to the popular marketing concept and strategic marketing orientation concepts, the authors define the Junzi concept as a business philosophy and Junzi orientation as the implementation of this philosophy. It proposes a Junzi orientation has a positive influence on companies' performances.

Design/methodology/approach

An 18-item scale comprising five dimensions: (1) Ren – benevolence, humaneness; (2) Yi – appropriateness, righteousness; (3) Li – propriety, harmonious differentiation; (4) Zhi – wisdom, knowledge management; and (5) Xin – integrity, trustworthiness, was developed to measure Junzi orientation. A total of 423 questionnaires were collected from different industries in Hong Kong, and confirmatory factor analyses were conducted.

Findings

The multidimensional behavioral construct of Junzi orientation scale was reliable and valid. The data supported that Junzi orientation has a positive influence on companies' performances.

Practical implications

The paper suggests that Junzi orientation could enhance a firm's competitive advantage.

Originality/value

This paper develops a culturally sensitive business orientation scale based on Chinese Confucianism and normative ethics.
Examining the consequences of adaptive selling behavior by door-to-door salespeople in the Korean cosmetic industry
Authors: Amenuvor Fortune Edem , Yi Ho-Taek , Boateng Henry
Published: August 2021

Purpose

This paper aims to assess the effect of adaptive selling behavior on customer outcomes, mutual outcomes and salesperson outcomes.

Design/methodology/approach

The respondents were salespeople and customers in selected door-to-door cosmetics companies in South Korea. A questionnaire was used to collect the data. Structural equation modeling was used to analyze the data in this study.

Findings

Findings show that adaptive selling behavior positively affects customer satisfaction, customer loyalty, sales performance, job satisfaction and relationship quality. These findings suggest that adaptive selling is crucial for the firm's survival depending on the industry and the product. Additionally, unlike previous studies, the authors use salespeople's self-reporting responses and customer-reporting of salespeople, which further enhances the richness and uniqueness of the results.

Originality/value

Studies investigating mutual outcomes of adaptive selling behavior are scarce. The study also emphasizes that adaptive selling behavior enhances salesperson outcomes and customer outcomes and primarily uses dyadic data between door-to-door salespeople and their customers, which is not very common.
Auditor tenure, investor protection and accounting quality: international evidence
Authors: Kamarudin Khairul Anuar , Wan Ismail Wan Adibah , Ariff Akmalia M.
Published: August 2021

Purpose

This study aims to investigate whether auditor tenure has a significant influence on accounting quality and whether investor protection moderates the effect of auditor tenure on accounting quality.

Design/methodology/approach

This study uses weighted least squares regression on a sample of 77,855 firm-year observations from 36 countries during the period 2010–2016. This study uses the absolute value of performance-matched discretionary accruals to measure financial reporting quality.

Findings

This study finds that a longer auditor tenure is associated with higher accounting quality, thus supporting the knowledge effect arguments. The results on the joint effect of investor protection and auditor tenure show evidence of the substitutive effect of investor protection, where the positive impact of auditor tenure on accounting quality is weaker in a high investor-protection environment.

Practical implications

These findings provide input for policy implications involving the auditing profession. Regulators may need to weigh the costs and benefits of mandatory audit rotation because country-level institutional factors influence auditing regulations and practices, as well as the auditors’ behaviors.

Originality/value

This study adds to the limited, albeit important, evidence on the joint effect of auditor tenure and country-level governance on accounting quality. The authors respond to the call by Brooks et al. (2017) for more evidence on the role of audits on financial reporting outcomes across various legal institutions for creating effective policies.
Do sustainability practices influence financial performance? Evidence from the Nordic financial industry
Authors: Rahi ABM Fazle , Akter Ruzlin , Johansson Jeaneth
Published: August 2021

Purpose

The purpose of this study is to explore the impact of sustainability (environmental, social and governance or ESG) practices on the financial performance (FP) of the Nordic financial industry.

Design/methodology/approach

The study covers a sample selection of observations for a total of 152 firm-years for 39 financial companies within the Nordic region (Sweden, Denmark, Finland and Norway) for the business years including 2015–2019. Data regarding ESG and FP indicators were extracted from the Thomson Reuters Eikon database in July 2020. This is a quantitative study using regression and a generalized method of moments.

Findings

Using static and dynamic estimators, the authors found both positive and negative impacts of sustainability practice on FP. The authors identified a negative relationship between ESG practices and FP (return on invested capital, return on equity and earnings per share). The authors identified a positive relationship between governance and return on assets.

Originality/value

A key contribution to the accounting literature is the finding that there is a risk for financial firms in adopting sustainability practices, as they follow a logic that contradicts the purely economic rationale. On the other hand, the positive relationship between governance and FP helps not only companies but also regulators and researchers to understand the positive impact of a good governance structure.