bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational engineering of industrial S. cerevisiae: towards xylitol production from sugarcane bagasse
Authors: da Silveira Bezerra de Mello Fellipe , Maneira Carla , Lizarazo Frank Uriel Suarez , Nagamatsu Sheila , Vargas Beatriz , Vieira Carla , Secches Thais , Coradini Alessando L V , de Carvalho Silvello Maria Augusta , Goldbeck Rosana , Pereira Gonçalo Amarante Guimarães , Teixeira Gleidson Silva 
Published: December 2021

ABSTRACTBACKGROUNDSugarcane hemicellulosic material is a compelling source of usually neglected xylose that could figure as feedstock to produce chemical building blocks of high economic value, such as xylitol. In this context, Saccharomyces cerevisiae strains typically used in the Brazilian bioethanol industry are a robust chassis for genetic engineering, given their robustness towards harsh operational conditions and outstanding fermentation performance. Nevertheless, there are no reports on the use of these strains for xylitol production using sugarcane hydrolysate.RESULTSPotential single-guided RNA off-targets were analyzed in two preeminent industrial strains (PE-2 and SA-1), providing a database of 5’-NGG 20 nt sequences, and guidelines for the fast and cost-effective CRISPR-editing of such strains. After genomic integration of a NADPH-preferring xylose reductase (XR), FMYX (SA-1 hoΔ::xyl1) and CENPKX (CEN.PK-122 hoΔ::xyl1) were tested in varying cultivation conditions for xylitol productivity to infer influence of the genetic background. Near-theoretical yields were achieved for all strains, however the industrial consistently outperformed the laboratory strain. Batch fermentation of raw sugarcane bagasse hydrolysate with remaining solid particles represented a challenge for xylose metabolization and 3.65 ± 0.16 g/L xylitol titre was achieved by FMYX. Finally, quantification of NADPH - cofactor implied in XR activity - revealed that FMYX has 33% more available cofactors than CENPKX.CONCLUSIONSAlthough widely used in several S. cerevisiae strains, this is the first report of CRISPR-Cas9 editing major yeast of the Brazilian bioethanol industry. Fermentative assays of xylose consumption revealed that NADPH availability is closely related to mutant strains’ performance. We also pioneer the use of sugarcane bagasse as a substrate for xylitol production. Finally, we demonstrate how industrial background SA-1 is a compelling chassis for the second-generation industry, given its inhibitor tolerance and better redox environment that may favor production of reduced sugars.
MeasureIce: Accessible on-the-fly measurement of ice thickness in cryo-electron microscopy
Authors: Brown Hamish G. , Hanssen Eric 
Published: December 2021

AbstractIce thickness is arguably one of the most important factors limiting the resolution of protein structures determined by cryo electron microscopy. The amorphous atomic structure of the ice that stabilizes and protects biological samples in cryo-EM grids also imprints some addition noise in the TEM images. Ice that is too thick jeopardizes the success of particle picking and reconstruction of the biomolecule in the worst case and, at best, deteriorates eventual map resolution. Minimizing the thickness of the ice layer and thus the magnitude of its noise contribution is thus imperative in cryo-EM grid preparation. In this paper we introduce MeasureIce, a simple, easy to use ice thickness measurement tool for screening and selecting acquisition areas of cryo-EM grids. We show that it is possible to simulate thickness-image intensity look-up tables using elementary scattering physics and thereby adapt the tool to any microscope without time consuming experimental calibration. We benchmark our approach using two alternative techniques: the “ice-channel” technique and tilt-series tomography. We also demonstrate the utility of ice thickness measurement for selecting holes in gold grids containing an Equine apoferritin sample, achieving a 1.88 Ångstrom resolution in subsequent refinement of the atomic map.
Transcriptomic modulation in response to an intoxication with deltamethrin in Triatoma infestans, vector of Chagas disease
Authors: Traverso Lucila , Latorre Estivalis Jose Manuel , Fernandes Gabriel da Rocha , Fronza Georgina , Lobbia Patricia , Cueto Gastón Mougabure , Ons Sheila 
Published: December 2021

AbstractBackgroundTriatoma infestans is the main vector of Chagas disease in the Southern Cone. The resistance to pyrethroid insecticides developed by populations of this species impairs the effectiveness of vector control campaigns in wide regions of Argentina. The study of the global transcriptomic response to pyrethroid insecticides is important to deepen the knowledge about detoxification in triatomines.Methodology and findingsWe used RNA-Seq to explore the early transcriptomic response of T. infestans after intoxication with deltamethrin. We were able to assemble a complete transcriptome of this vector and found evidence of differentially expressed genes belonging to diverse families such as chemosensory and odorant-binding proteins, ABC transporters and heat-shock proteins. Moreover, genes related to transcription and translation, energetic metabolism and cuticle rearrangements were also modulated. Finally, we characterized the repertoire of previously uncharacterized detoxification-related gene families in T. infestans and Rhodnius prolixus.Conclusions and significanceOur work contributes to the understanding of the detoxification response in vectors of Chagas disease. Given the absence of genomic information from T. infestans, the analysis presented here constitutes a resource for molecular and physiological studies in this species. The results increase the knowledge on detoxification processes in vectors of Chagas disease, and provide relevant information to explore new potential insecticide resistance mechanisms in these insects.Author summaryChagas disease affects millions of people worldwide. In the Southern Cone, the development of pyrethroid resistant populations from T. infestans is related to vector persistence and affects the efficiency of vector control campaigns. Several studies have explored the causes of insecticide resistance in T. infestans populations. However, the global transcriptomic response after insecticide treatment has not been analyzed in this species so far. In this study, we obtained transcriptomic information which allowed us to characterize important gene families despite the absence of genomic information. Furthermore, we performed a quantitative analysis of gene expression after deltamethrin intoxication. The results provided here increase the knowledge on detoxification processes in vectors of Chagas disease, which is essential for the design of new vector control strategies.
CFIm25 regulates human stem cell function independently of its role in mRNA alternative polyadenylation
Authors: Ran Yi , Huang Shanshan , Shi Junjie , Feng Qiumin , Deng Yanhui , Xiang Andy Peng , Yao Chengguo 
Published: December 2021

AbstractIt has recently been shown that CFIm25, a canonical mRNA 3’ processing factor, could play a variety of physiological roles through its molecular function in the regulation of mRNA alternative polyadenylation (APA). Here, we used CRISPR/Cas9-mediated gene editing approach in human embryonic stem cells (hESCs) for CFIm25, and obtained three gene knockdown/mutant cell lines. CFIm25 gene editing resulted in higher proliferation rate and impaired differentiation potential for hESCs, with these effects likely to be directly regulated by the target genes, including the pluripotency factor rex1. Mechanistically, we unexpected found that perturbation in CFIm25 gene expression did not significantly affect cellular mRNA 3’ processing efficiency and APA profile. Rather, we provided evidences that CFIm25 may impact RNA polymerase II (RNAPII) occupancy at the body of transcribed genes, and promote the expression level of a group of transcripts associated with cellular proliferation and/or differentiation. Further study indicated that CFIm25 association with LEO1, an RNAPII associated factor, might contribute to the effect. Taken together, these results reveal novel mechanisms underlying CFIm25’s modulation in determination of cell fate, and provide evidence that the process of mammalian gene transcription may be regulated by an mRNA 3’ processing factor.
Biophysical Characterisation of Human LincRNA-p21 Sense and Antisense Alu Inverted Repeats
Authors: D’Souza Michael H. , Mrozowich Tyler , Badmalia Maulik D. , Geeraert Mitchell , Frederickson Angela , Henrickson Amy , Demeler Borries , Wolfinger Michael T. , Patel Trushar R. 
Published: December 2021

AbstractHuman Long Intergenic Noncoding RNA-p21 (LincRNA-p21) is a regulatory noncoding RNA that plays an important role in promoting apoptosis. LincRNA-p21 is also critical in down-regulating many p53 target genes through its interaction with a p53 repressive complex. The interaction between LincRNA-p21 and the repressive complex is likely dependent on the RNA tertiary structure. Previous studies have determined the two-dimensional secondary structures of the sense and antisense human LincRNA-p21 AluSx1 IRs using SHAPE. However, there were no insights into its three-dimensional structure. Therefore, we in vitro transcribed the sense and antisense regions of LincRNA-p21 AluSx1 Inverted Repeats (IRs) and performed analytical ultracentrifugation, size exclusion chromatography, light scattering, and small angle X-ray scattering (SAXS) studies. Based on these studies, we determined low-resolution, three-dimensional structures of sense and antisense LincRNA-p21. By adapting previously known two-dimensional information, we calculated their sense and antisense high-resolution models and determined that they agree with the low-resolution structures determined using SAXS. Thus, our integrated approach provides insights into the structure of LincRNA-p21 Alu IRs. Our study also offers a viable pipeline for combining the secondary structure information with biophysical and computational studies to obtain high-resolution atomistic models for long noncoding RNAs.
A dynamic model of the ABA Signaling pathway with its core components: translation rate of PP2C determines the kinetics of ABA-induced gene expression
Authors: Ndathe Ruth , Dale Renee , Kato Naohiro 
Published: December 2021

SummaryThe abscisic acid (ABA) signaling pathway is the key defense mechanism against drought stress in plants, yet the connectivity of cellular molecules related to gene expression in response to ABA is little understood. A dynamic model of the core components of the ABA signaling pathway was built using ordinary differential equations to understand the connectivity. Parameter values of protein-protein interactions and enzymatic reactions in the model were implemented from the data obtained by previously conducted experiments. On the other hand, parameter values of gene expression and translation were determined by comparing the kinetics of gene expression in the model to those of ABA-induced RD29A (response to desiccation 29A) in actual plants. Based on the analyses of the optimized model, we hypothesized that the translation rate of PP2C (protein phosphatase type 2C) is downregulated by ABA to increase the ABRE (ABA-responsive element) promoter activity. The hypotheses were preliminarily supported by newly conducted experiments using transgenic Arabidopsis plants that carry a luciferase expression cassette driven by the RD29A promoter (RD29A::LUC). The model suggests that identifying a mechanism that alters PP2C translation rate would be one of the next research frontiers in the ABA signaling pathway.
Pre-determined diversity in resistant fates emerges from homogenous cells after anti-cancer drug treatment
Authors: Goyal Yogesh , Dardani Ian P. , Busch Gianna T. , Emert Benjamin , Fingerman Dylan , Kaur Amanpreet , Jain Naveen , Mellis Ian A. , Li Jingxin , Kiani Karun , Fane Mitchell E. , Weeraratna Ashani T. , Herlyn Meenhard , Raj Arjun 
Published: December 2021

AbstractEven amongst genetically identical cancer cells, therapy resistance often only emerges from a very small subset of those cells. Much effort has gone into uncovering the molecular differences in rare individual cells in the initial population that may allow certain cells to become therapy resistant; however, comparatively little is known about variability in the resistant outcomes themselves. Here, we develop and apply FateMap, a framework that combines DNA barcoding with single-cell RNA sequencing to reveal the fates of hundreds of thousands of clones exposed to anti-cancer therapies. We show that resistant clones emerging from single-cell-derived cancer cells adopt molecularly, morphologically, and functionally distinct fate types. These different resistant types are largely predetermined by molecular differences between cells before addition of drug and not by extrinsic cell-specific microenvironmental factors. Changes in dose and kind of drug can, however, switch the resistant fate type of an initial cell, even resulting in the generation and elimination of certain fate types. Diversity in resistant fates was observed across several single-cell-derived cancer cell lines and types treated with a variety of drugs. Cell fate diversity as a result of variability in intrinsic cell states may be a generic feature of response to external cues.
Assessing single-component gene drive systems in the mosquito Aedes aegypti via single generation crosses and modeling
Authors: Reid William , Williams Adeline E , Sanchez-Vargas Irma , Lin Jingyi , Juncu Rucsanda , Olson Ken E , Franz Alexander WE 
Published: December 2021

ABSTRACTThe yellow fever mosquito Aedes aegypti is a major vector of arthropod-borne viruses, including dengue, chikungunya, and Zika. A novel approach to mitigate arboviral infections is to generate mosquitoes refractory to infection by overexpressing antiviral effector molecules. Such an approach requires a mechanism to spread these antiviral effectors through a population, for example, by using CRISPR/Cas9-based gene drive (GD) systems. Critical to the design of a single-locus autonomous GD is that the selected genomic locus be amenable to both GD and appropriate expression of the antiviral effector. In our study, we used reverse engineering to target two intergenic genomic loci, which had previously shown to be highly permissive for antiviral effector gene expression, and we further investigated the use of three promoters (nanos, β2-tubulin, or zpg) for Cas9 expression. We then quantified the accrual of insertions or deletions (indels) after single generation crossings, measured maternal effects, and assessed fitness costs associated with the various transgenic lines to model the rate of GD fixation. Overall, MGDrivE modeling suggested that when an autonomous GD is placed into an intergenic locus, the GD system will eventually be blocked by the accrual of GD blocking resistance alleles and ultimately be lost in the population. Moreover, while genomic locus and promoter selection were critically important for the initial establishment of the autonomous GD, it was the fitness of the GD line that most strongly influenced the persistence of the GD in the simulated population. As such, we propose that when autonomous CRISPR/Cas9 based GD systems are anchored in an intergenic locus, they temporarily result in a strong population replacement effect, but as GD-blocking indels accrue, the GD becomes exhausted due to the fixation of CRISPR resistance alleles.Significance statementFor the purpose of population replacement, CRISPR/Cas9 based gene drives (GD) have been developed in Anopheles spp. and split GDs have been developed in Ae. aegypti. In our study, we developed autonomous GD in Ae. aegypti and positioned the drives in intergenic loci ideal for the expression of antiviral effector genes. Our results suggest that when the GD is placed into an intergenic locus, there is rapid introgression of the GD resulting in a transient population replacement followed by loss of the drive as resistance alleles accrue. Fitness of the transgenic lines and maternal deposition of CRISPR/Cas9 components were the major contributing factors affecting the perseverance of the GD in our population models.
Opposing steroid signals modulate protein homeostasis through deep changes in fat metabolism in Caenorhabditis elegans
Authors: Gómez-Escribano AP , Mora-Martínez C , Roca M , Walker DS , Panadero J , Sequedo MD , Saini R , Knölker HJ , Blanca J , Burguera J , Lahoz A , Cañizares J , Millán JM , Burton N , Schafer WR , Vázquez-Manrique RP 
Published: December 2021

ABSTRACTProtein homeostasis is crucial for viability of all organisms, and mutations that enhance protein aggregation cause different human pathologies, including polyglutamine (polyQ) diseases, such as some spinocerebellar ataxias or Huntington disease. Here, we report that neuronal Stomatin-like protein UNC-1 protects against aggregation of prone-to-aggregate proteins, like polyQs, α-synuclein and β-amyloid, in C. elegans. UNC-1, in IL2 neurons, antagonizes the function of the cytosolic sulfotransferase SSU-1 in neurohormonal signalling from ASJ neurons. The target of this hormone is the nuclear hormone receptor NHR-1, which acts cell-autonomously to protect from aggregation in muscles. A second nuclear hormone receptor, DAF-12, functions oppositely to NHR-1 to maintain protein homeostasis. Transcriptomics analyses reveal deep changes in the expression of genes involved in fat metabolism, in unc-1 mutants, which are regulated by NHR-1. This suggest that fat metabolism changes, controlled by neurohormonal signalling, contributes to modulate protein homeostasis.
Blockchain technology design in accounting: Game changer to tackle fraud or technological fairy tale?
Authors: Centobelli Piera , Cerchione Roberto , Del Vecchio Pasquale , Oropallo Eugenio , Secundo Giustina 
Published: December 2021

PurposeThis paper aims to design, build and evaluate a blockchain platform in the accounting domain, taking an ecosystem perspective. To achieve this aim, the research provides evidence for developing a decentralised architecture rooted on blockchain technology, designing a proof of concept and modelling an accounting blockchain-based system.Design/methodology/approachMoving from the analysis of previous literature and leveraging on the design science approach, this paper provides a framework grounded on the main pillars of blockchain and accounting functions, identifying technical and non-technical issues that must be addressed embrace blockchain technology's full potential.FindingsWe propose and discuss a conceptual framework for a blockchain-based accounting context, moving from the identification of a typical accounting scenario. The framework is organised around three scalable levels: the first level is a technological infrastructure based on a distributed database with peer-to-peer storage; second, in the intermediate level, increasing control levels are assured through permissions and validation and third, in the higher level, the system provides the integration of business and security applications. The deployment of this system relies on a private network of nodes that validates transactions.Practical implicationsThe proposed conceptual framework about blockchain development in accounting allows closing the knowledge gap between blockchain developers and accounting experts by suggesting technological and strategic issues for practitioners.Originality/valueWe provide practical guidelines to design and adopt blockchain in the accounting domain.
Reflections on neo-Kaleckian growth regimes: a Marxian reproduction perspective
Authors: Zhao Feng , Tian Jiahe , Duan Yuchen 
Published: December 2021

PurposeThe neo-Kaleckian model follows the ideas of Marx, Keynes and Kalecki, that investment is a key influencing factor in the dynamics of the capitalist mode of production. Through the discussion of different forms of investment decision function, this paper constructs the analysis framework of wage-led and profit-led economic growth regimes.Design/methodology/approachThe model has become an important theoretical paradigm for current Western heterodox economists regarding the research on the impact of functional income distribution on economic growth, and it has a very large impact on both theoretical and empirical research. Starting from Marx's reproduction theory, this article discusses the theoretical shortcomings of the neo-Kaleckian growth regime model.FindingsThis paper mainly focuses on three aspects: (1) the ideological legacy of “Smith's Dogma”; (2) neglecting the restrictions on income distribution from the organic composition of capital and the surplus value rate; (3) technological progress and the formation of a new long economic wave.Originality/valueThe authors believe that the neo-Kaleckian model unilaterally emphasizes the demand-side factors in the economy and, unconsciously or not, ignores the role of the supply-side, which makes it encounter certain limitations in explaining long-term growth. Even if some empirical conclusions are employed to bridge functional income distribution and technological progress, there is still a lack of a theoretical basis for accurately describing long-term economic changes using this model. In order to better promote high-quality economic development and accelerate the formation of a new pattern of economic development in which the domestic large-scale cycle is the mainstay and the domestic and international double cycles promote each other, the authors need to adopt a policy combination with the supply-side as the main and the demand-side as the supplement, and to work from both sides.
Effects of built environment on healing the mental health of the people–literature review
Authors: Pragati S. , Shanthi Priya R. , Rajagopal Prashanthini , Pradeepa C. 
Published: December 2021

PurposeThe coronavirus disease 2019 (COVID-19) pandemic has been reported to have a major impact on the mental health of an individual. Healing the mental stress, anxiety, depression and insomnia of an individual's immediate surroundings play a major role. Therefore, this study reviews how the built environment impacts the healing of an individual's state of mind.Design/methodology/approachVarious works of literature on healing environments were analysed to create frameworks that can facilitate psychological healing through architectural elements. Articles were selected from various journals like SAGE, PubMed,Journalof Appliedand ComputationalMechanics(JACM), Routledge Taylor and Francis,Journal of Contemporary Urban Affairs (JCUA), ScienceDirect, and Emerald databases, news articles, official web pages, and magazines that have been referred.FindingsIndicators (spatial, sensory comfort, safety, security, privacy and social comfort) are linked to sub-indicators (access, distractions and views) and design characteristics (indoor climate, interior view, outside view, privacy, communication, noise, daylighting, temperature) which help in better connection of the built environment with individual's mental health. From the above indicators, sub-indicators and design characteristics, the authors have come to a conclusion that a view to the outside with better social interaction has an in-depth effect on an individual's mental health.Research limitations/implicationsThis study predominantly talks about healing in hospitals but quarantining of COVID-19 patients happens in residences too. So, it is important to find the healing characteristics in residences and in which typology the recovery process is high.Originality/valueThis paper has been written completely by the author and the co-authors and has not been copied from any other sources.