bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epistasis shapes the fitness landscape of an allosteric specificity switch
Authors: Nishikawa Kyle K. , Hoppe Nicholas , Smith Robert , Bingman Craig , Raman Srivatsan 
Published: October 2020

AbstractEpistasis is a major determinant in the emergence of novel protein function. In allosteric proteins, direct interactions between inducer-binding mutations propagate through the allosteric network, manifesting as epistasis at the level of biological function. Elucidating this relationship between local interactions and their global effects is essential to understanding evolution of allosteric proteins. We integrate computational design, structural and biophysical analysis to characterize the emergence of novel inducer specificity in an allosteric transcription factor. Adaptive landscapes of different inducers of the engineered mutant show that a few strong epistatic interactions constrain the number of viable sequence pathways, revealing ridges in the fitness landscape leading to new specificity. Crystallographic evidence shows a single mutation drives specificity by reshaping the binding pocket. Comparison of biophysical and functional landscapes emphasizes the nonlinear relationship between local inducer affinity and global function (allostery). Our results highlight the functional and evolutionary complexity of allosteric proteins.
Biochemical Validation of a Fourth Guanidine Riboswitch Class in Bacteria
Authors: Salvail Hubert , Balaji Aparaajita , Yu Diane , Roth Adam , Breaker Ronald R. 
Published: October 2020

ABSTRACTAn intriguing consequence of ongoing riboswitch discovery efforts is the occasional identification of metabolic or toxicity response pathways for unusual ligands. Recently, we reported the experimental validation of three distinct bacterial riboswitch classes that regulate gene expression in response to the selective binding of a guanidinium ion. These riboswitch classes, called guanidine-I, -II and -III, regulate numerous genes whose protein products include previously misannotated guanidine exporters and enzymes that degrade guanidine via an initial carboxylation reaction. Guanidine is now recognized as the primal substrate of many multidrug efflux pumps that are important for bacterial resistance to certain antibiotics. Guanidine carboxylase enzymes had long been annotated as urea carboxylase enzymes but are now understood to participate in guanidine degradation. Herein we report the existence of a fourth riboswitch class for this ligand, called “guanidine-IV”. Members of this class use a novel aptamer to selectively bind guanidine and use an unusual expression platform arrangement that is predicted to activate gene expression when ligand is present. The wide distribution of this abundant riboswitch class, coupled with the striking diversity of other guanidine-sensing RNAs, demonstrates that many bacterial species maintain sophisticated sensory and genetic mechanisms to avoid guanidine toxicity. This finding further highlights the mystery regarding the natural source of this nitrogen-rich chemical moiety.
Molecular determinants for α-tubulin methylation by SETD2
Authors: Kearns Sarah , Mason Frank M. , Rathmell W. Kimryn , Park In Young , Walker Cheryl , Verhey Kristen , Cianfrocco Michael A. 
Published: October 2020

AbstractPost-translational modifications to tubulin are important for many microtubule-based functions inside cells. A recently identified tubulin modification, methylation, occurs on mitotic spindle microtubules during cell division, and is enzymatically added to tubulin by the histone methyltransferase SETD2. We used a truncated version of human SETD2 (tSETD2) containing the catalytic SET and C-terminal Set2 Rpb1 interacting (SRI) domains to investigate the biochemical mechanism of tubulin methylation. We found that recombinant tSETD2 has a higher activity towards tubulin dimers than polymerized microtubules. Using recombinant single-isotype tubulin, we demonstrate that methylation is restricted to lysine 40 (K40) of α-tubulin. We then introduced pathogenic mutations into tSETD2 to probe the recognition of histone and tubulin substrates. A mutation in the catalytic domain, R1625C, bound to tubulin but could not methylate it whereas a mutation in the SRI domain, R2510H, caused loss of both tubulin binding and methylation. We thus further probed a role for the SRI domain in substrate binding and found that mutations within this region had differential effects on the ability of tSETD2 to bind to tubulin versus RNA Polymerase II substrates, suggesting distinct mechanisms for tubulin and histone methylation by SETD2. Lastly, we found that substrate recognition also requires the negatively-charged C-terminal tail of α-tubulin. Together, this work provides a framework for understanding how SETD2 serves as a dual methyltransferase for histone and tubulin methylation.
Structural basis of inhibition of a putative drug efflux transporter NorC, through a single-domain camelid antibody
Authors: Kumar Sushant , Athreya Arunabh , Gulati Ashutosh , Nair Rahul Mony , Penmatsa Aravind 
Published: October 2020

AbstractMulti-drug efflux is a major mechanism of acquiring antimicrobial resistance among superbugs. In this study, we report the X-ray structure of NorC, a 14 transmembrane major facilitator superfamily member that is implicated in fluoroquinolone resistance in drug-resistantStaphylococcus aureusstrains, at a resolution of 3.6 Å. The NorC structure was determined in complex with a single-domain camelid antibody that interacts at the extracellular face of the transporter and stabilizes it in an outward-open conformation. The complementarity determining regions of the antibody enter and block solvent access to the interior of the vestibule, thereby inhibiting alternating-access. NorC specifically interacts with an organic cation, tetraphenylphosphonium, although it does not demonstrate an ability to transport it. The interaction is compromised in the presence of NorC-antibody complex, consequently establishing a strategy to detect and block NorC and related efflux pumps through the use of single- domain camelid antibodies.
Yeast Ssd1 is a non-enzymatic member of the RNase II family with an alternative RNA recognition interface
Authors: Bayne Rosemary A. , Jayachandran Uma , Kasprowicz Aleksandra , Bresson Stefan , Tollervey David , Wallace Edward W. J. , Cook Atlanta G. 
Published: October 2020

AbstractThe conserved fungal RNA binding protein Ssd1, is important in stress responses, cell division and virulence. Ssd1 is closely related to Dis3L2 of the RNase II family of nucleases, but lacks catalytic activity and may act by suppressing translation of associated mRNAs. Previous studies identified motifs that are enriched in Ssd1-associated transcripts, yet the sequence requirements for Ssd1 binding are not well understood. Here we present the crystal structure of Ssd1 at 1.9 Å resolution. Active RNase II enzymes have a characteristic, internal RNA binding path, but in Ssd1 this is blocked by remnants of regulatory sequences. Instead, RNA binding activity has likely been relocated to the outer surface of the protein. Usingin vivocrosslinking and cDNA analysis (CRAC), we identify Ssd1-RNA binding sites. These are strongly enriched in 5’UTRs of a subset of mRNAs encoding cell wall proteins. Based on these and previous analyses, we identified a conserved bipartite motif that binds Ssd1 with high affinityin vitro. These studies provide a new framework for understanding the function of a pleiotropic post-transcriptional regulator of gene expression and give insights into the evolution of regulatory elements in the RNase II family.
Fluorescent tagging ofPlasmodiumcircumsporozoite protein allows imaging of sporozoite formation but blocks egress from oocysts
Authors: Singer Mirko , Frischknecht Friedrich 
Published: October 2020

AbstractThe circumsporozoite protein, CSP is the major surface protein ofPlasmodiumsporozoites, the form of malaria parasites transmitted by mosquitoes. CSP is involved in sporozoite formation within and egress from oocysts, entry into mosquito salivary glands and mammalian liver as well as migration in the skin. Antibodies against CSP can stop infection prior to the first round of parasite replication in the liver. CSP consists of different domains and is proteolytically cleaved prior to hepatocyte invasion. Part of CSP has been developed into a licensed vaccine against malaria. Yet, how CSP facilitates sporozoite formation, oocyst egress and hepatocyte specific invasion is still not fully understood. Here, we generated a series of parasites expressing full-length versions of CSP as fusion proteins with the green fluorescent protein. This enabled the investigation of sporozoite formation in living oocysts and revealed a dominant negative function of some GFP-CSP fusions during sporozoite egress.
Characterization of potassium, sodium and their interactions effects in yeasts
Authors: Illarionov Aleksandr , Lahtvee Petri-Jaan , Kumar Rahul 
Published: October 2020

AbstractBiotechnology requires efficient microbial cell factories. The budding yeastSaccharomyces cerevisiaeis an important cell factory but for a sustainable use of natural resources more diverse cellular attributes are essential. Here, we benchmarked non-conventional yeastsKluyveromyces marxianus(KM) andRhodotorula toruloides(RT) against the extensively characterized strains ofS. cerevisiae, CEN.PK and W303. We developed a computational method for the characterization of cell/vacuole volumes and observed an inverse relationship between the maximal growth rate and the median cell volume that was responsive to monovalent cations. We found that the supplementation of certain K+concentrations to CEN.PK cultures containing 1.0 M Na+increased the specific growth rate by four-fold with a parabolic shift in the median cell/vacuole volumes. The impairment of ethanol and acetate utilization in CEN.PK, acetate in W303, at the higher K+/Na+concentrations implied an interference in the metabolic pathways required for their consumption. In RT cultures, the supplementation of K+/Na+induced a trade-off in glucose utilization but alleviated cellular aggregates formation where specified cationic concentrations increased the beta-carotene yield by 60% compared with the reference. Our comparative analysis of cell/vacuole volumes using exponential phase cultures showed that the median volumes decreased the most for KM and the least for RT in response to studied cations. Noteworthy for the implication in aging research using yeasts, the vacuole to cell volume ratio increased with the increase in cell volume for W303 and KM, but not for CEN.PK and RT.ImportanceFor designing efficient bioprocesses characterization of microbial cell factories in the relevant culture environment is important. The control of cell volume in response to salt stress is crucial for the productivity of microbial cell factories. We developed an open source computational method for the analysis of optical microscopy images that allowed us to quantify changes in cell/vacuole volumes in response to common salts in yeasts. Our study provides a framework for appreciating the role of cellular/organellar volumes in response to changing physiological environment. Our analysis showed that K+/Na+interactions could be used for improving the cellular fitness of CEN.PK and increasing the productivity of beta-carotene inR. toruloides, which is a commercially important antioxidant and a valuable additive in foods.
Lowest emission sustainable aviation biofuels as the potential replacement for the Jet-A fuels
Authors: A. Anderson , A. Karthikeyan , C. Ramesh Kumar , S. Ramachandran , T.R. Praveenkumar 
Published: October 2020

Purpose
The purpose of this study is to predict the performance and emission characteristics of micro gas turbine engines powered by alternate fuels. The micro gas turbine engine performance, combustion and emission characteristics are analyzed for the jet fuel with different additives.

Design/methodology/approach
The experimental investigation was carried out with Jet A-1 fuel on the gas turbine engines at different load conditions. The primary blends of the Jet A-1 fuels are from canola and solid waste pyrolysis oil. Then the ultrasonication of highly concentrated multiwall carbon nanotubes is carried with the primary blends of canola (Jet-A fuel 70%, canola 20% and 10% ethanol) and P20E (Jet-A 70% fuel, 20% PO and 10% ethanol).

Findings
The consumption of the fuel is appreciable with the blends at a very high static thrust. The 39% reduction in thrust specific fuel consumption associated with a 32% enhance in static thrust with P20E blend among different fuel blends. Moreover, due to the increase in ethanol concentration in the blends PO20E and C20E lead to a 22% rise in thermal efficiency and a 9% increase in higher oxygen content is observed.

Practical implications
The gas turbine engine emits very low emission of gases such as CO, CO2 and NOx by using the fuel blends, which typically reduces the fossil fuel usage limits with reduced pollutants.

Originality/value
The emission of the gas turbine engines is further optimized with the addition of hydrogen in Jet-A fuel. That is leading to high specific fuel exergy and owing to the lower carbon content in the hydrogen fuel when compared with that of the fossil fuels used in gas turbine engines. Therefore, the usage of hydrogen with nanofluids was so promising based on the results obtained for replacing fossil fuels.
Flavonoid enrichment of fresh-cut apple through osmotic dehydration-assisted impregnation
Authors: Lopez Ma. Michelle L. , Morais Rui M.S.C. , Morais Alcina M.M.B. 
Published: October 2020

PurposeInclusion of bioactive compounds in food products is promising for developing novel functional food products. The feasibility of incorporating flavonoids and low-calorie sugar substitutes in fresh-cut apple through osmotic dehydration (OD) was investigated.Design/methodology/approachThe impregnation of quercetin and fisetin in apple cubes was tested. The effects of different osmotic agents, sucrose and sorbitol:mannose, on the water loss (WL) and sugar gain of the samples were studied at 25 and 40 °C for eight hours.FindingsTemperature was a significant factor in the mass transfer kinetics, that is to say, higher temperatures resulting in higher rates. The molecular weight of the solutes in the osmotic solution also affected the OD kinetics and flavonoids uptake, as well as the physico-chemical quality.Originality/valueOverall, the results indicate that OD using alternative low-calorie and health-promoting solutes can be an effective treatment to simultaneously enrich fresh-cut apples with senolytic flavonoids, therefore presenting a great potential for a novel functional food product.
Technological innovation research in the last six decades: a bibliometric analysis
Authors: Akbari Morteza , Khodayari Maryam , Khaleghi Armin , Danesh Mozhgan , Padash Hamid 
Published: October 2020

PurposeThis study aims to explore the evolutionary trajectories of technological innovation using 1,361 documents to determine the most cited documents, influential authors, prominent journals and leading countries in the field of technological innovation research.Design/methodology/approachIn this paper, the intellectual structure of technological innovation literature was studied using bibliometric co-occurrence and co-citation analyses. The authors focused on the 1,361 documents in this research stream published between 1961 and 2019.FindingsThe findings show that researchers do not appropriately draw on theoretical perspectives external to the field to study different dimensions of technological innovation. This study reveals six distinct areas within the literature: sources of innovation, environmental innovation and technological innovation, investment, economic growth of countries, technological innovation systems for sustainable development, innovation system, research and development and competitiveness.Originality/valueThis study investigates the foundations of the conception, themes and research communities within the technological innovation domain. This paper found strong evidence that technological innovation is one of the keys to the research area in innovation studies.
Methods in assessing the values of architecture in residential neighbourhoods
Authors: Spoormans Lidwine , Pereira Roders Ana 
Published: October 2020

PurposeAlthough residential neighbourhoods are the largest and most resilient share of a city and the process of urban conservation and renewal is ongoing, methods to assess their values are limited. This paper presents the results of a systematic literature review, revealing the state of the art and its knowledge gaps with regard to methods for assessing values of architecture in residential neighbourhoods.Design/methodology/approachThe systematic literature review is based on studies selected by a research protocol, using a digital database of peer-reviewed literature. A metanarrative approach is used to synthesise the qualitative data from reviewed articles. This review has two stages: (1) giving an overview of the field and (2) categorising research methods and disciplines.FindingsThe review revealed a wide variety of studies from different disciplines and deduced its key trends, titled as “storylines”, concerning the methods to assess significance, integrating a broader scope of values and different perspectives. In particular, the “storylines” outside traditional heritage disciplines offer methods to include more stakeholders, link value assessment to policy development or highlight heritage potential. Results reveal the diversity in concepts and strengthen the need for an interdisciplinary vocabulary on values and methods, enabling planners and policymakers to compare their results and help to create more attractive and resilient cities.Originality/valueBy reviewing and comparing the selected studies from a wider range of disciplines and research fields, this paper shares insights into the complementary characteristics of the different types of value research, outlining the added value of the different perspectives.
Satisfying consumers all around: a multidisciplinary view of omnichannel retail
Authors: Wang Juan , Zheng Bowen , Liu Hefu 
Published: October 2020

PurposeOmnichannel retail are catching increasing attention from multiple research area, due to its widespread and essential application in retailing industry. The principal object of this paper is to systematically review current studies on omnichannel retail in information systems, operations and marketing research area. Further, the second purpose of this study is to provide insights and guides on omnichannel research to facilitate advance research in the area.Design/methodology/approachA systematic review on omnichannel retail in retailing industry has been conducted. 33 research articles from 2014 to 2020 from Financial Times 50 journals (FT 50 journals) were identified to be reviewed. The articles were reviewed on the basis of study area namely: information systems, operations and marketing. These research areas were further divided into subcategories to provide in-depth and crystal clear review of literature.FindingsThe review outcome showed that omnichannel topics are active in management studies. There are three main research areas: information systems, operations management and marketing. This study found that IT enhances channel capabilities and expands demand in omnichannel retail; operations can be better optimized based on understanding of cross-channel interactions, product category and retailer types; consumer heterogeneity, product category, channel capabilities and retailer type are all found to contribute to complexities of omnichannel marketing.Originality/valueThis study provides a pioneering review to gauge the updated literature concerned with omnichannel research in terms of IT, operations and marketing perspective. Further, a systematic literature review provides insights and guides for future significant studies on potential research subjects.
An empirical study of the influence of individual-related factors on undergraduates' academic burnout: Malaysian context
Authors: Lau Sook Cheng , Chow Hon Jie , Wong Siew Chin , Lim Chui Seong 
Published: October 2020

PurposeThe purpose of this study is to examine the relationship between perfectionism, self-efficacy, coping strategies and academic burnout among Malaysian undergraduates in higher education institutions.Design/methodology/approachData were collected from 251 respondents who were public and private university undergraduates. Partial least square structural equation modelling (PLS-SEM) was used to investigate the influences of coping strategies, perfectionism and self-efficacy on academic burnout among undergraduates.FindingsThe results showed that all independent variables, namely coping strategies, perfectionism and self-efficacy are statistically correlated to academic burnout.Research limitations/implicationsThis article provides an empirical framework for explaining the academic burnout of undergraduates’ based on the review of related career works of literature.Practical implicationsTo provide insights in order to improve understanding of existing stress models and provide practical implications for local higher education institutions and undergraduates to reduce academic burnout.Social implicationsThe study seeks to enhance awareness and destigmatise the mental health issues of undergraduates, which is important to help them to maintain a healthy lifestyle and well-being.Originality/valueThis paper offers new insight to identify the predictors of academic burnout among undergraduates from Malaysian higher education institutions.
Does terrorism hamper FDI inflows? A pre and post 9/11 analysis
Authors: Arif Imtiaz , Rawat Amna Sohail , Khan Lubna 
Published: October 2020

PurposeThis research intends to determine the role of terrorism in defying foreign direct investment (FDI) in top terror effected economies.Design/methodology/approachPanel data on FDI and terrorism from top terror effected economies spanning from 1987 to 2018 were used and the relationship for whole sample was investigated. Later the sample period was divided into pre (1987–2001) and post 9/11 (2002–2018) subsample and same relationship was tested to investigate the normalization of terror effect on FDI. The method of Pooled Mean Group (PMG) was used to test the hypothesis.FindingsThe results showed a negative but statistically insignificant impact of terrorism on the FDI inflows in the long run. Later the sample period was divided into pre (1987–2001) and post 9/11 (2002–2018) subsample. The empirical estimates for pre and post 9/11 periods indicated a negative and statistically significant relationship between terrorism and FDI for pre 9/11 period, and a negative but statistically insignificant relationship between the two variables for post 9/11 period.Originality/valueThe findings suggest several important policy implications for the terror affected countries and are further discussed in the study.