bluuebunny/crossref_metadata_2025_split huggingface dataset:
The H3K4me1 histone mark recruits DNA repair to functionally constrained genomic regions in plants
Authors: Quiroz Daniela , Lopez-Mateos Diego , Zhao Kehan , Pierce Alice , Ortega Lissandro , Ali Alissza , Carbonell-Bejerano Pablo , Yarov-Yarovoy Vladimir , Monroe J. Grey 
Published: May 2022

AbstractMutation is the ultimate source of genetic variation. Mutation rate variability has been observed within plant genomes, but the underlying mechanisms have been unclear. We previously found that mutations occur less often in functionally constrained regions of the genome inArabidopsis thalianaand that this mutation rate reduction is predicted by H3K4me1, a histone modification found in the gene bodies of actively expressed and evolutionarily conserved genes in plants. We reanalyzedde novogermline single base substitutions in fast neutron irradiated mutation accumulation lines in Kitaake rice (Oryza sativa) and found the same reduction in mutations associated with H3K4me1, gene bodies, and constrained genes as inA. thaliana, suggesting conserved mechanisms for mutation reduction in plants. Here, we characterize a model of targeted DNA repair to explain these observations; PDS5C and MSH6 DNA repair-related proteins target H3K4me1 through their Tudor domains, resulting in nearby DNA experiencing elevated repair. Experimental data andin-silicomodeling support the high affinity of the Tudor domain for H3K4me1 in both proteins, and that this affinity is conserved between plant species. ChIP-seq data from PDS5C confirms its localization to conserved and low mutation rate genome regions. Somatic and germline mutations observed by deep sequencing of wild-type andMSH6knockout lines confirm that MSH6 preferentially repairs gene bodies and H3K4me1-enriched regions. These findings inspire further research to characterize the origins of mechanisms of targeted DNA repair in eukaryotes and their consequences on tuning the evolutionary trajectories of genomes.
Elevated temperatures reduce population-specific transcriptional plasticity in developing lake sturgeon (Acipenser fulvescens)
Authors: Bugg William S. , Thorstensen Matt J. , Marshall Katie E. , Anderson W. Gary , Jeffries Ken M. 
Published: May 2022

AbstractRising mean and variance in temperatures elevate threats to endangered freshwater species such as lake sturgeon,Acipenser fulvescens. Previous research demonstrated that higher temperatures during development result in physiological consequences for lake sturgeon populations throughout Manitoba, Canada, with alteration of metabolic rate, thermal tolerance, transcriptional responses, growth, and mortality. We acclimated lake sturgeon (30 – 60 days post fertilization, a period of high mortality) from northern and southern populations (56° 02′ 46.5″ N, 96° 54′ 18.6″ W and 50° 17′ 52″ N, 95° 32′ 51″ W respectively, separated by approximately 650 km) within Manitoba to current (summer highs of 20-23°C) and future projected (+2-3°C) environmental temperatures of 16, 20, and 24°C for 30 days, and measured gill transcriptional responses using RNAseq. Transcripts revealed SNPs consistent with genetically distinct populations and transcriptional responses altered by acclimation temperature. There were a higher number of differentially expressed transcripts observed in the southern, compared to the northern, population as temperatures increased, indicating enhanced transcriptional plasticity. Both lake sturgeon populations responded to elevated acclimation temperatures by downregulating the transcription of genes involved in protein synthesis and energy production. Further, there were population-specific thresholds for the downregulation of processes promoting transcriptional plasticity as well as mitochondrial function as the northern population showed decreases at 20°C, while this capacity was not diminished until 24°C in the southern population. These transcriptional responses highlight the molecular impacts of increasing temperatures for divergent lake sturgeon populations during vulnerable developmental periods and the critical influence of transcriptome plasticity on acclimation capacity.
Characterization of Plasmodium falciparum myosin B in complex with the calmodulin-like domain of its light chain MLC-B
Authors: Pires Isa , Hung Yu-Fu , Bergmann Ulrich , Molloy Justin E. , Kursula Inari 
Published: May 2022

AbstractMyosin B (MyoB) is a class 14 myosin expressed in all invasive stages of the malaria parasite, Plasmodium falciparum. It is not associated with the glideosome complex that drives motility and invasion of host cells. During red blood cell invasion, it remains at the apical tip of the merozoite but is no longer observed once invasion is completed. MyoB is not essential for parasite survival but, when it is knocked out, merozoites are delayed in the initial stages of red blood cell invasion, giving rise to a growth defect that correlates with reduced invasion success. Here, we have expressed and purified functional MyoB with the help of parasite-specific chaperones Hsp90 and Unc45, characterized its binding to actin and its known light chain MLC-B using biochemical and biophysical methods, and determined its low-resolution structure in solution using small-angle X-ray scattering. In addition to MLC-B, four other putative regulatory light chains were found to bind to the MyoB IQ2 motif in vitro. The purified recombinant MyoB adopted the overall shape of a myosin, exhibited actin-activated ATPase activity, and moved actin filaments in vitro. The ADP release rate was faster than the ATP turnover number, and thus, does not appear to be rate-limiting. This, together with the observed high affinity to actin and the specific localization of MyoB, may point towards a role in tethering and/or force sensing during early stages of invasion.
Response of sleep slow oscillations to acoustic stimulation is evidenced by distinctive synchronization processes
Authors: Navarrete Miguel , Osorio-Forero Alejandro , Gómez Angela , Henao David , Le Van Quyen Michel , Valderrama Mario 
Published: May 2022

ABSTRACTClosed loop acoustic stimulation (CLAS) during sleep has shown to boost slow wave (SW) amplitude and spindle power. Moreover, sleep SW are suggested to be classified based on different processes of neuronal synchronization. Following this, different types of SW events may have distinct functional roles and be differentially affected by external stimuli. However, the SW synchronization processes affected by CLAS are not well understood. Here, we studied the effect of CLAS on the dissociation of SW events based on two features of neuronal synchronization in the EEG (topological spread and wave slope). We evaluated and classified individual SW events of fourteen healthy subjects during a CLAS stimulated (STM) and a control night (CNT). Three main categories of SW events were found denoting (C1) steep-slope SW with global spread, (C2) flat-slope waves with localized spread and homeostatic regulation, and (C3) multipeaked flat-slope events with global spread. Comparing between conditions, we found a consistent increase of event proportion and trough amplitudes for C1 events during the time of stimulation. Furthermore, we found similar increases in post-stimulus spectral power in θ, β and σ frequencies for CNT vs STIM condition independently of sleep stage or SW categories. However, topological analysis showed differentiated spatial dynamics in N2 and N3 for SW categories and the co-occurrence with spindle events. Our findings reveal the nature of post-stimulus SW and suggest that CLAS boosts SW amplitudes by increasing neuronal synchronization of wave troughs, leading thus the post-stimulus SW-spindle co-occurrence.
A new enzymatic assay to quantify inorganic pyrophosphate in plasma
Authors: Lundkvist Stefan , Niaziorimi Fatemeh , Szeri Flora , Caffet Matthew , Terry Sharon F. , Johansson Gunnar , Jansen Robert S. , van de Wetering Koen 
Published: May 2022

AbstractInorganic pyrophosphate (PPi) is a crucial extracellular mineralization regulator. Low plasma PPi concentrations underlie the soft tissue calcification present in several rare hereditary mineralization disorders as well as in more common conditions like chronic kidney disease and diabetes. Even though deregulated plasma PPi homeostasis is known to be linked to multiple human diseases, there is currently no reliable assay for its quantification. We here describe an PPi assay that employs the enzyme ATP sulfurylase to convert PPi into ATP. Generated ATP is subsequently quantified by firefly luciferase-based bioluminescence. An internal ATP standard was used to correct for sample-specific interference by matrix compounds on firefly luciferase activity. The assay was validated and shows excellent precision (<3.5%) and accuracy (93-106%) of PPi spiked into human plasma samples. We found that of several anticoagulants tested only EDTA effectively blocked conversion of ATP into PPi in plasma after blood collection. Moreover, filtration over a 300,000 Da molecular weight cut-off membrane, reduced variability of plasma PPi and removed ATP present in a membrane-enclosed compartment, possibly platelets. Applied to plasma samples of wild type and Abcc6-/- rats, an animal model with established low circulating levels of PPi, the new assay showed lower variability than the assay that was previously in routine use in our laboratory.In conclusion, we here report a new and robust assay to determine PPi concentrations in plasma, which outperforms currently available assays because of its high sensitivity, precision, and accuracy.
Uncertainty Quantification in COVID-19 Detection Using Evidential Deep Learning
Authors: Khosravi Bardia , Faghani Shahriar , Ashraf-Ganjouei Amir 
Published: May 2022

AbstractConsidering the immense pace of developments in deep learning (DL), its applications in medicine are relatively limited. One main issue that hinders the utilization of DL in the medical practice workflow is its reliability. A radiologist interpreting an image can easily say “I don’t know”, while a DL model is forced to output a result. Evidential deep learning (EDL) is one of the methods for uncertainty quantification (UQ). In this work, we aimed to use EDL to express model uncertainty in detecting COVID-19. We used SIIM-FISABIO-RSNA COVID-19 chest x-ray dataset and trained a model to diagnose typical COVID-19 pneumonia. When applied to a separate test set, it yielded an accuracy of 88% with median uncertainty scores of 0.25 and 0.07 for normal and typical COVID-19 images, respectively. Moreover, the model labeled unseen indeterminate and atypical COVID-19 x-rays with median uncertainties of 0.32 and 0.35, respectively. Our model’s performance was superior to the exact model trained with conventional approach of DL (i.e., using the cross-entropy loss), which is not able to express the uncertainty level. Overall, this study demonstrates applicability of UQ in disease detection that could facilitate the use of DL in practice by increasing its reliability.
Echinocandin heteroresistance causes prophylaxis failure and facilitates breakthroughCandida parapsilosisinfection
Authors: Zhai Bing , Liao Chen , Jaggavarapu Siddharth , Tang Yuanyuan , Rolling Thierry , Ning Yating , Sun Tianshu , Bergin Sean A. , Gjonbalaj Mergim , Miranda Edwin , Babady N. Esther , Bader Oliver , Taur Ying , Butler Geraldine , Zhang Li , Xavier Joao B. , Weiss David S. , Hohl Tobias M. 
Published: May 2022

AbstractBreakthrough infections of patients on antimicrobial prophylaxis represent a significant and often unexplained cause of morbidity. Here, we reveal that in high-risk patients on micafungin prophylaxis heteroresistance – the presence of a phenotypically unstable, low frequency subpopulation of resistant cells (∼1 in 10,000) – underlies breakthrough bloodstream infections byCandida parapsilosismisclassified as susceptible by standard antimicrobial susceptibility testing. By analyzing 219 clinicalC. parapsilosisisolates from North America, Europe, and Asia, we demonstrate widespread micafungin heteroresistance. To facilitate detection of micafungin heteroresistance, we constructed a predictive machine learning framework that classifies isolates as heteroresistant or susceptible by a maximum of ten genomic features. Our results connect heteroresistance to unexplained prophylaxis failure and demonstrate a proof-of-principle diagnostic approach with the potential to inform clinical decisions.
The expression and function of 28s5-rtsRNA: an update
Authors: Wang Yi , Zhao Yanjie , Li Shuai 
Published: May 2022

AbstractOur previous research identified an abundant 28s rRNA 5’ terminal derived small RNA (named 28s5-rtsRNA), which could decrease multiple ribosomal protein mRNA levels. In the last several years, the development of novel high-throughput RNA sequencing methods, exampled as PANDORA-seq, has changed the repertoire of small RNAs. In the present study, we reanalyzed the PANDORA-seq data by using a sRNAbench bioinformatic tool and revealed that 28s5-rtsRNA was among the most abundant small RNAs, particularly after T4PNK treatment during sequencing library preparation. 28s5-rtsRNA pairing with 5.8s rRNA 3’ terminal derived small RNA could also decrease multiple ribosomal mRNA levels. At last, we performed a mutational scan to identify the key nucleotides involved in the 28s5-rtsRNA duplex function.
Direct detection of RNA repair by nanopore sequencing
Authors: White Laura K. , Strugar Saylor M. , MacFadden Andrea , Hesselberth Jay R. 
Published: May 2022

AbstractLigation by plant and fungal RNA ligases yields an internal 2′-phosphate group on each RNA ligation product. In budding yeast, this covalent mark occurs at the splice junction of two targets of ligation: intron-containing tRNAs and the messenger RNA HAC1. The repertoire of RNA molecules repaired by RNA ligation has not been explored due to a lack of unbiased approaches for identifying RNA ligation products. Here, we define several unique signals produced by 2′-phosphorylated RNAs during nanopore sequencing. A 2′-phosphate at the splice junction of HAC1 mRNA inhibits 5′→3′ degradation, enabling detection of decay intermediates in yeast RNA repair mutants by nanopore sequencing. During direct RNA sequencing, intact 2′-phosphorylated RNAs produce diagnostic changes in nanopore current properties and base calling features, including stalls produced as the modified RNA translocates through the nanopore motor protein. These approaches enable directed studies to identify novel RNA repair events from multiple species.
The impact of green supply chain management practices on environmental performance during COVID-19 period: the case of discretionary companies in the G-20 countries
Authors: El Khoury Rim , Nasrallah Nohade , Atayah Osama F. , Dhiaf Mohamed Mahjoub , Frederico Guilherme F. 
Published: May 2022

PurposeThis study investigates the impact of green supply chain management (GSCM) practices on environmental performance in firms operating in the discretionary sector in the G20 countries. The sample covers 749 firms for the period 2010–2020.Design/methodology/approachThis study combines qualitative and quantitative data to examine the impact of the implementation of GSCM on accounting performance measured by the operating margin (OM) and return on assets (ROA). The authors also moderate the effects of Six Sigma and quality management (QM) and ISO 9000 and control for firm variables and COVID 19.FindingsUsing a panel data regression and structural equation modeling (SEM), results indicate that discretionary firms with internal solid GSCM practices combined with external environmental monitoring of suppliers are likely to outperform their peers in environmental issues. Using hierarchical regression, results indicate that both ISO 9000 and S&QM have moderating effects at some level of performance. Furthermore, environmental performance is positively correlated with accounting performance. This study contributes to the literature by addressing the impact of GSCM and the importance of reinforcing green and social regulations to protect the planet.Originality/valueThe paper is one of the first to measure GSCM triple components and account for COVID-19 in the context of discretionary companies and G20 countries. It highlights the impact of green initiatives to cope with major disruptions and decrease pollution and environmental disasters.
Managing resilience of micro, small and medium enterprises (MSMEs) during COVID-19: analysis of barriers
Authors: Gupta Anchal , Kumar Singh Rajesh 
Published: May 2022

PurposeMicro, small and medium enterprises (MSMEs) are facing major difficulties with working capital, need of digitalisation and lack of skilled workforce during this crisis situation. Managing resilience post pandemic is again a huge challenge for MSMEs. Therefore, the main objective of the study is to identify the critical barriers for recovery of MSMEs from the pandemic outbreak and recommending potential solutions for avoiding vulnerabilities.Design/methodology/approachThe most significant barriers, which will impact MSMEs resilience issues are extracted from vast literature review, discussed with nine experts from MSMEs and further categorised into organisational, operational and technical barriers. Best–worst method (BWM) has been used to find the importance rating of barriers for developing resilience in MSMEs.FindingsIt can be observed that the organisational barriers (0.507) are the most significant, followed by operational barriers (0.300) and then, technological barriers (0.192). Liquidity crunch and inadequate technical skills of employees are the most significant barriers for MSMEs resilience during COVID-19, whereas fluctuation in input cost, unavailability of containers on time and decreased process efficiency are the least significant barriers for recovering MSMEs post COVID-19.Practical implicationsFindings imply that MSMEs should try to overcome major barriers such as resource constraints, lack of skills and knowledge and inefficient inventory planning.Originality/valueFindings of study will be of immense use for MSMEs in efficient management of operations and in developing resilience during uncertain business environment.
The influence of effort level on profit distribution strategies in IPD projects
Authors: Guo Shuwen , Wang Junwu , Xiong Huaping 
Published: May 2022

PurposeConstruction projects have become increasingly long, complex and costly with waste and inefficiencies and often fail to achieve the desired results. Integrated project delivery (IPD) is believed to change these problems. A reasonable and fair profit distribution mechanism is a critical factor for ensuring the success of the IPD projects. This study aims to investigate the strategies of all participants in the profit distribution of an IPD project with respect to the factor of the effort level.Design/methodology/approachThis study describes the influence of owners and participants on profit distribution due to their respective efforts in the IPD project alliance. The influence of effort level on profit distribution is discussed based on the Holmstrom-Milgrom model of asymmetric information game theory and principal-agent theory, combined with incentive compatibility (IC) constraints and individual rationality (IR) constraints.FindingsThe results show that the optimal level of effort by each participant optimizes the profit distribution of an IPD project. At the same time, in the revenue incentive contract, the effort level of the participants is positively correlated with the profit distribution, proportional to their contribution coefficient and inversely proportional to the square of the cost of their creative activities in terms of effort. Each party of an IPD project can adopt a series of measures to improve their own effort level and choose the optimal level of effort based on the profit distribution, while satisfying their own utility maximization.Originality/valueThis study introduces the Holmstrom-Milgrom model in the principal-agent theory to explore the influence of the effort level on profit distribution in IPD projects. The quantitative model can contribute to establish a fair and efficient profit distribution scheme for the IPD projects.
How are social procurement actors shaping a new field of professional practice in the Australian construction industry?
Authors: Loosemore Martin , Keast Robyn , Barraket Jo 
Published: May 2022

PurposeSocial procurement is becoming an increasing policy focus for governments around the world as they seek to incentivise new collaborative partnerships with private organisations in industries like construction to meet their social obligations. The limited construction management research in this area shows that the successful implementation of these policies depends on a new generation of social procurement professionals who are promoting these policies into an institutional vacuum with little organisational identity, legitimacy and support. The purpose of this paper is to investigate what these actors do to promote and build support for the implementation of these policies in their organisations.Design/methodology/approachA thematic analysis of in-depth semi-structured interviews with 15 social procurement actors in the Australian construction industry is presented.FindingsResults portray an experimental, disconnected and nascent institutional field of practice with a high degree of role ambiguity and conflict. In the absence of a clear organisational identity and legitimate power-base, social procurement actors are forced to rely on incremental rather than radical innovation and the power of stories to persuade others to engage with their vision for creating social value through construction.Originality/valueContributing new insights to the emerging “practice theme” in social procurement research, this paper provides important conceptual and practical information about the attributes which determine their success, how they fit into existing organisational structures and how they build support to achieve enabling institutional change. Academically, the results advance understanding of how social procurement professionals are implementing these policies into their organisations. Practically, they provide new information which enable social procurement professionals to improve their practices and construction companies to recruit the right people into these roles and design their organisations to more effectively support them.
The dual pressures of youth and expansion: revisiting stage theories of growth in SMEs
Authors: Wilkinson Adrian , Muurlink Olav , Townsend Keith , Peetz David 
Published: May 2022

Purpose The authors consider stage theories of human resource management (HRM) to explore how new companies experiencing high levels of growth face the dual pressures of youth and expansion.Design/methodology/approachThe firms in this study are a sub-group of small and medium enterprises (SMEs) called “gazelles”. While this is a qualitative study, participants were chosen through a modified random sampling approach that ensures that the sample is representative of a regional population of gazelle firms.FindingsNew companies experiencing high levels of growth face the challenge of expansion while structurally immature. While the selected companies were ill-equipped in formal knowledge of HR they reacted to rapidly changing conditions and were forced to organisational flexibility meaning that few absolute rules were adopted.Originality/valueGazelle literature tends to focus on impediments to growth, rather than HR staples such as recruiting and retaining staff. But the studied cases showed an acute appreciation by gazelle managers of the value of motivated, skilled staff able to turn their hand to the fluctuating requirements of the fast-growing firm and a desire to establish formal HR mechanisms as part of the response to the stress of growth.