bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modelling spatiotemporal trends in the frequency of genetic mutations conferring insecticide target-site resistance in African malaria vector species
Authors: Hancock Penelope A. , Lynd Amy , Wiebe Antoinette , Devine Maria , Essandoh Johnathan , Wat’senga Francis , Manzambi Emile Z. , Agossa Fiacre , Donnelly Martin J. , Weetman David , Moyes Catherine L. 
Published: September 2021

ABSTRACTResistance in malaria vectors to pyrethroids, the most widely used class of insecticides for malaria vector control, threatens the continued efficacy of vector control tools. Target-site resistance is an important genetic resistance mechanism caused by mutations in the voltage-gated sodium channel (Vgsc) gene that encodes the pyrethroid target-site. Understanding the geographic distribution of target-site resistance, and temporal trends across different vector species, can inform strategic deployment of vector control tools. Here we develop a Bayesian statistical spatiotemporal model to interpret species-specific trends in the frequency of the most common resistance mutations, Vgsc-995S and Vgsc-995F, in three major malaria vector species Anopheles gambiae, An. coluzzii, and An. arabiensis. For nine selected countries, we develop annual predictive maps which reveal geographically-structured patterns of spread of each mutation at regional and continental scales. The results show associations, as well as stark differences, in spread dynamics of the two mutations across the three vector species. The coverage of ITNs was an influential predictor of Vgsc allele frequencies in our models. Our mapped Vgsc allele frequencies are a significant partial predictor of phenotypic resistance to the pyrethroid deltamethrin in An. gambiae complex populations, highlighting the importance of molecular surveillance of resistance mechanisms.
Magnetic DNA random access memory with nanopore readouts and exponentially-scaled combinatorial addressing
Authors: Lau Billy , Chandak Shubham , Roy Sharmili , Tatwawadi Kedar , Wootters Mary , Weissman Tsachy , Ji Hanlee P. 
Published: September 2021

ABSTRACTThe storage of data in DNA typically involves encoding and synthesizing data into short oligonucleotides, followed by reading with a sequencing instrument. Major challenges include the molecular consumption of synthesized DNA, issues with basecalling errors, and limitations with scaling up read access operations for individual data elements. Addressing these challenges, we describe a DNA storage system called MDRAM (Magnetic DNA-based Random Access Memory) that enables repetitive and efficient readouts of targeted files with nanopore-based sequencing. Through conjugation of synthesized DNA to magnetic beads, we enabled repeated readouts of data while preserving the original DNA analyte and maintaining data readout quality. MDRAM also utilizes an efficient convolutional coding scheme that leverages soft information in raw nanopore sequencing signals to achieve information reading costs comparable to Illumina sequencing despite substantially higher error rates. Finally, we demonstrate a proof-of-concept DNA-based proto-filesystem that enables an exponentially-scalable data address space using only small numbers of targeting primers for assembly and readout.ONE-SENTENCE SUMMARYWe demonstrate a novel DNA data storage system that leverages conjugation of DNA onto magnetic beads, new computational advances in data encoding, and exponentially scalable access of individual data elements.
Predicting base editing outcomes using position-specific sequence determinants
Authors: Pallaseni Ananth , Peets Elin Madli , Koeppel Jonas , Weller Juliane , Crepaldi Luca , Allen Felicity , Parts Leopold 
Published: September 2021

AbstractNucleotide-level control over DNA sequences is poised to power functional genomics studies and lead to new therapeutics. CRISPR/Cas base editors promise to achieve this ability, but the determinants of their activity remain incompletely understood. We measured base editing frequencies in two human cell lines for two cytosine and two adenine base editors at ∼14,000 target sequences. Base editing activity is sequence-biased, with largest effects from nucleotides flanking the target base, and is correlated with measures of Cas9 guide RNA efficiency. Whether a base is edited depends strongly on the combination of its position in the target and the preceding base, with a preceding thymine in both editor types leading to a wider editing window, while a preceding guanine in cytosine editors and preceding adenine in adenine editors to a narrower one. The impact of features on editing rate depends on the position, with guide RNA efficacy mainly influencing bases around the centre of the window, and sequence biases away from it. We use these observations to train a machine learning model to predict editing activity per position for both adenine and cytosine editors, with accuracy ranging from 0.49 to 0.72 between editors, and with better generalization performance across datasets than existing tools. We demonstrate the usefulness of our model by predicting the efficacy of potential disease mutation correcting guides, and find that most of them suffer from more unwanted editing than corrected outcomes. This work unravels the position-specificity of base editing biases, and provides a solution to account for them, thus allowing more efficient planning of base edits in experimental and therapeutic contexts.
Single residue substitution in protamine 1 disrupts sperm genome packaging and embryonic development in mice
Authors: Moritz Lindsay , Schon Samantha B. , Rabbani Mashiat , Sheng Yi , Pendlebury Devon F. , Agrawal Ritvija , Sultan Caleb , Jorgensen Kelsey , Zheng Xianing , Diehl Adam , Ragunathan Kaushik , Hu Yueh-Chiang , Nandakumar Jayakrishnan , Li Jun Z. , Boyle Alan P. , Orwig Kyle E. , Redding Sy , Hammoud Saher Sue 
Published: September 2021

SummaryConventional dogma presumes that protamine-mediated DNA compaction in sperm is achieved by passive electrostatics between DNA and the arginine-rich core of protamines. However, phylogenetic analysis reveals several non-arginine residues that are conserved within, but not across, species. The functional significance of these residues or post-translational modifications are poorly understood. Here, we investigated the functional role of K49, a rodent-specific lysine residue in mouse protamine 1 (P1) that is acetylated early in spermiogenesis and retained in sperm. In vivo, an alanine substitution (P1 K49A) results in ectopic histone retention, decreased sperm motility, decreased male fertility, and in zygotes, premature P1 removal from paternal chromatin. In vitro, the P1 K49A substitution decreases protamine-DNA binding and alters DNA compaction/decompaction kinetics. Hence, a single amino acid substitution outside the P1 arginine core is sufficient to profoundly alter protein function and developmental outcomes, suggesting that protamine non-arginine residues are essential to ensure reproductive fitness.
Arabidopsis uORF-containing mRNAs behave differently from NMD targets
Authors: Wu Hsin-Yen Larry , Hsu Polly Yingshan 
Published: September 2021

ABSTRACTUpstream ORFs (uORFs) are common regulatory elements in the 5’ untranslated regions of eukaryotic mRNAs. In addition to repressing main ORF translation, uORF translation in animals also reduces mRNA stability through nonsense-mediated decay (NMD). In contrast, the roles of uORFs in plants are less understood. Here, we identified actively translated uORFs (TuORFs) in Arabidopsis through ribosome profiling and systematically examined their roles in gene expression. Like animal systems, Arabidopsis TuORFs are associated with 38%, 14%, and 43% reductions in translation efficiency, mRNA half-lives, and protein levels, respectively. However, we found TuORF-containing mRNAs have 51% higher transcript levels, and this phenomenon is persistent in diverse tissues and developmental stages across plants. We present multiple lines of evidence that indicate Arabidopsis uORF-containing mRNAs generally exhibit distinct behavior from known NMD targets. First, TuORF-containing mRNAs are not increased in NMD mutants. Second, TuORF-containing mRNAs and known NMD targets have distinct expression patterns, and they are translationally repressed via different mechanisms. Finally, TuORF- containing mRNAs and NMD targets are degraded through separate pathways. Our results suggest that Arabidopsis TuORFs reduce mRNA stability and translation through mechanisms different from NMD and highlight a fundamental difference in gene regulation mediated by TuORFs in plants and animals.
Comparative transcriptomics of sevenImpatiensspecies
Authors: Šurinová Mária , Stočes Štepán , Dostálek Tomáš , Jarošová Andrea , Münzbergová Zuzana 
Published: September 2021

AbstractImpatiensis a genus containing more than 1000 species. Thanks to its size, it is a unique system for studying species diversification in natural populations. This study focused on the characterization of novel transcriptomes from sevenImpatiensspecies originating from Nepal. Leave transcriptome ofImpatines balsaminaL., I. racemosaDC., I. bicornutaWall, I. falciferHook, I. devendraePusalkar,I. scullyiHook andI. scabridaDC were sequenced and compared. Reads werede novoassembled and aligned to 92 035-226 081 contigs. We identified 14 728 orthology groups shared among all the species and 3 020 which were unique to a single species. In single species, 2536-3009 orthology groups were under selection from which 767 were common for all species. Six of the seven investigated species shared 77% of gene families withI. bicornutabeing the most distinct species. Specific gene families involved in response to different environmental stimuli were closely described.Impatiens bicornutaselection profile shared selection on zing finger protein structures and flowering regulation and stress response proteins with the other investigated species. Overall, the study showed substantial similarity in patterns of selections on transcribed genes across the species suggesting similar evolutionary pressures. This suggests that the species group may have evolved via adaptive radiation.
Development of a machine learning model to estimate biotic ligand model-based predicted no□effect concentrations for copper in freshwater
Authors: Chung Jiwoong , Yoo Geonwoo , Choi Jinhee , Lee Jong-Hyeon 
Published: September 2021

AbstractThe copper biotic ligand model (BLM) has been used for environmental risk assessment by taking into account the bioavailability of copper in freshwater. However, the BLM-based environmental risk of copper has been assessed only in Europe and North America, with monitoring datasets containing all of the BLM input variables. For other areas, it is necessary to apply surrogate tools with reduced data requirements to estimate the BLM-based predicted no-effect concentration (PNEC) from commonly available monitoring datasets. To develop an optimized PNEC estimation model based on an available monitoring dataset, an initial model that considers all BLM variables, a second model that requires variables excluding alkalinity, and a third model using electrical conductivity as a surrogate of the major cations and alkalinity have been proposed. Furthermore, deep neural network (DNN) models have been used to predict the nonlinear relationships between the PNEC (outcome variable) and the required input variables (explanatory variables). The predictive capacity of DNN models in this study was compared with the results of other existing PNEC estimation tools using a look-up table and multiple linear and multivariate polynomial regression methods. Three DNN models, using different input variables, provided better predictions of the copper PNECs compared with the existing tools for four test datasets, i.e., Korean, United States, Swedish, and Belgian freshwaters. The adjusted r2 values in all DNN models were higher than 0.95 in the test datasets, except for the Swedish dataset (adjusted r2 > 0.87). Consequently, the most applicable model among the three DNN models could be selected according to the data availability in the collected monitoring database. Because the most simplified DNN model required only three water quality variables (pH, dissolved organic carbon, and electrical conductivity) as input variables, it is expected that the copper BLM-based risk assessment can be applied to monitoring datasets worldwide.
Sonic hedgehog is essential for proximal-distal outgrowth of the limb bud in salamanders
Authors: Purushothaman Sruthi , Lopez Aviña Brianda B. , Seifert Ashley W. 
Published: September 2021

AbstractThe developing forelimb has been a foundational model to understand how specified progenitor cells integrate genetic information to produce the tetrapod limb bauplan (1, 2). Although the reigning hypothesis is that all tetrapods develop limbs in a similar manner, recent work suggests that urodeles have evolved a derived mode of limb development (3-5). Here we demonstrate through pharmacological and genetic inactivation of Sonic hedgehog (Shh) signaling in axolotls that Shh directs expansion and survival of limb progenitor cells in addition to patterning the limb across the proximodistal and antero-posterior axis. In contrast to inactivation of Shh in mouse or chick embryos where a humerus, radius and single digit develop (6-9), Shh crispant axolotls completely lack forelimbs. In rescuing limb development by implanting SHH-N protein beads into the nascent limb field of Shh-crispants, we show that the limb field is specified in the absence of Shh and that hedgehog pathway activation is required to initiate proximodistal outgrowth. When the derived nature of salamander limb development is placed in a phylogenetic context, it generates a new hypothesis where the ability to regenerate an entire tetrapod limb may have evolved uniquely among urodeles.TeaserShh is essential for salamander limb development
IRE1α drives lung epithelial progenitor dysfunction to establish a niche for pulmonary fibrosis
Authors: Auyeung Vincent C. , Downey Michael S. , Kathiriya Jaymin , Thamsen Maike , Wenger Talia A. , Backes Bradley J. , Brumwell Alexis , Chapman Harold A. , Sheppard Dean , Papa Feroz R. 
Published: September 2021

AbstractIdiopathic pulmonary fibrosis (IPF) is a disease of progressive interstitial fibrosis, which leads to severe debilitation, respiratory failure, and death. In IPF, environmental exposures interact with genetic risk factors to engender critical patho-etiological events in lung epithelial cells, including endoplasmic reticulum (ER) stress and TGFβ signaling, but the interactions between these disparate pathways are not well understood. We previously showed that kinase inhibitors of the IRE1α bifunctional kinase/RNase—a central mediator of the unfolded protein response (UPR) to ER stress—protected mice from bleomycin-induced pulmonary fibrosis. Here we show that a nanomolar-potent, mono-selective kinase inhibitor of IRE1α (KIRA8) decreases ER-stress induced TGFβ signaling and the senescence-associated secretory phenotype (SASP) in the lung epithelium after bleomycin exposure. A recently-described subset of “damage-associated transient progenitors” (DATPs) display IRE1α-regulated pathological gene signatures that are quelled by KIRA8, in vivo. After injury, these cells uniquely express integrin αvβ6, a key activator of TGFβ in pulmonary fibrosis. KIRA8 inhibition of IRE1α decreases both DATP number and Itgb6 expression in remaining cells, with a decrease in local collagen accumulation. Single-cell RNA sequencing from IPF lungs revealed an analogous Itgb6+ cell population that may also be regulated by IRE1α. These findings suggest that lung epithelial progenitor cells sit at the center of the fibrotic niche, and IRE1α signaling locks them into a dysfunctional state that establishes and perpetuates pathological fibrosis.
The role of performance measurement in assessing the contribution of circular economy to the sustainability of a wine value chain
Authors: Cavicchi Caterina , Vagnoni Emidia 
Published: September 2021

PurposeThis study aims to ascertain the extent to which a cooperative controlling a wine supply chain implements a performance measurement system (PMS) that monitors the effects of a circular economy (CE) strategy, developed through partnerships, on the economic and environmental sustainability of the value chain.Design/methodology/approachThe study analyzes the characteristics of the closed-loop business model and uses the PMS to assess the contribution of CE partnerships to the sustainability of the value chain. The case study is based on interviews conducted on the cooperative's top management and supplemented with an analysis of external reports, related documents and direct observations.FindingsThe PMS was underpinned by enterprise resource planning (ERP), through which CE indicators control for the benefits generated on behalf of the cooperative and its CE partners.Originality/valueGiven the paucity of the studies that address the performance measurement of CE at the supply chain level and its relation to sustainability, this study sheds light on the role that PMS can play in tracking the contribution of CE partnerships to the sustainability of a wine value chain operating in agro-waste valorization. Furthermore, the performance measurement of the CE strategy contributes to an assessment of the responsible production of sustainable development goals at the supply chain level.
Exploring internal organisational communication dynamics in the professional football industry
Authors: Manoli Argyro Elisavet , Hodgkinson Ian Richard 
Published: September 2021

PurposeRelative to the increasing focus on organisations’ outward communication consistency and coherency, the internal communication taking place between different organisational functions is under-explored. The study aims to address the following two research questions: What form does cross-functional communication take within organisations? How do features of the communication work climate influence the form of cross-functional communication?Design/methodology/approachThe study draws on qualitative data generated from semi-structured interviews with media and marketing managers from 33 professional football organisations operating in the English Premier League.FindingsThematic patterns between internal communication practices and different communication climates lead to the development of a new internal organisational communications typology, comprising: Type 1: collaborative symmetrical communication (cohesive climate); Type 2: unstructured informal communication (friendly climate); and Type 3: cross-functional silos (divisive climate).Originality/valueInternal organisational communication practices are deemed fundamental to organisational success, yet there remains limited empirical evidence of the form such practices take or how they interact with features of an organisation’s communication climate. The study introduces a new internal organisational communications typology to develop and extend the theory and practice of internal marketing communications.
Entrepreneurial intentions: the relevance of nature and nurture
Authors: Farrukh Muhammad , Raza Ali , Sajid Muhammad , Rafiq Muhammad , Hameed Rizwana , Ali Tanzila 
Published: September 2021

PurposeThis paper aims to investigate the role of nature and nurture in students’ entrepreneurial intention (EIs). In doing so, the study examines the relationship between prenatal testosterone exposure (2D:4D), risk-taking propensity, entrepreneurial self-efficacy and EIs. Moreover, the moderating role of entrepreneurial education between entrepreneurial self-efficacy and EI is also investigated.Design/methodology/approachIn line with previous studies on EI, the authors tested hypotheses based on quantitative data obtained from university students.FindingsData were analyzed with the help of the structural equation modeling technique, and the results revealed that all the hypothesized relationships were supported.Originality/valueThe field of entrepreneurship has become an attractive area of research for practitioners and academics. One tinted area of research in entrepreneurship is the investigation of EI because it is a good predictor of entrepreneurial behavior. Several antecedents of EIs have been recognized in the literature ranging from personality traits to environmental factors. However, less is known about the role of biology in entrepreneurship. Incorporating biological factors in the field of entrepreneurship appears to be theoretically viable and sound. Thus, this study investigates the effect of biological factors in the presence of psychological factors on EIs, which is a unique contribution to the literature on entrepreneurship.
Servitization in the creative and cultural industries
Authors: Sundbo Jon , Rubalcaba Luis , Gallouj Faïz 
Published: September 2021

Purpose
This paper aims to develop a conceptual framework for understanding the role of servitization in the creative and cultural industries (CCI).

Design/methodology/approach
A conceptual model is proposed based on five elements: servitization drivers (digitalization in particular), agents, modes (based on the standardization/customization dynamics), servitization mechanisms (the authors provide a new classification) and service experiences.

Findings
CCI is not considered a natural part of the service sector. They drive economic and social development and are part of the innovation ecosystem. They are confronting a set of emerging dynamics in which servitization plays a leading role. Servitization is a way to move toward value co-creation by transforming existing business models. Servitization – with digitalization facilitates the co-creation of CCI-based experiences for customers, users and other stakeholders.

Research limitations/implications
In terms of further research implications, these theoretical and managerial considerations call for empirical research of the servitization of CCI to investigate how and how much it develops.

Practical implications
CCI companies need new business models that combine servitization, digitalization and value co-creation in the right mix. “One size fits all” does not work. Business models have to consider the right mix.

Originality/value
The proposed conceptual model provides a novel understanding of servitization and CCI and changes the focus from the “production” or push side (e.g. artistic creativity and messages) that has characterized much CCI theory toward the demand or pull side and buyers’ (users) increased power.