bluuebunny/crossref_metadata_2025_split huggingface dataset:
Augmentation of extracellular ATP synergizes with chemotherapy in triple negative breast cancer
Authors: Manouchehri Jasmine M , Datta Jharna , Willingham Natalie , Wesolowski Robert , Stover Daniel , Ganju Ramesh K , Carson William , Ramaswamy Bhuvaneswari , Cherian Mathew A 
Published: January 2022

AbstractIntroductionBreast cancer affects two million women worldwide every year and is the most common cause of cancer-related death among women. The triple-negative breast cancer (TNBC) sub-type is associated with an especially poor prognosis because currently available therapies, fail to induce long-lasting responses. Therefore, there is an urgent need to develop novel therapies that result in durable responses. One universal characteristic of the tumor microenvironment is a markedly elevated concentration of extracellular adenosine triphosphate (eATP). Chemotherapy exposure results in further increases in eATP through its release into the extracellular space of cancer cells via P2RX channels. eATP levels are reduced by eATPases. Given that high concentrations of eATP are cytotoxic, we hypothesized that augmenting the release of eATP through P2RX channels and inhibiting extracellular ATPases would sensitize TNBC cells to chemotherapy.MethodsTNBC cell lines MDA-MB 231, Hs 578t and MDA-MB 468 and non-tumorigenic immortalized mammary epithelial MCF-10A cells were treated with increasing concentrations the chemotherapeutic agent paclitaxel in the presence of eATPase inhibitors, specific agonists or antagonists of P2RXs with cell viability and eATP content being measured. Additionally, the mRNA, protein and cell surface expressions of the purinergic receptors P2RX4 and P2RX7 were evaluated in all examined cell lines via qRT-PCR, western blot, and flow cytometry analyses, respectively.ResultsIn the present study, we observed dose-dependent declines in cell viability and increases in eATP in paclitaxel-treated TNBC cell lines in the presence of inhibitors of eATPases. These effects were reversed by specific antagonists of P2RXs. Similar results were observed with P2RX activators. All examined cell lines expressed both P2RX4 and P2RX7 at the mRNA, protein and cell surface levels.ConclusionThese results reveal that eATP modulates the chemotherapeutic response in TNBC cell lines which could be exploited to enhance the efficacy of chemotherapy regimens for TNBC.
Hydrogen production in the presence of oxygen by Escherichia coli K-12
Authors: Metcalfe George D. , Sargent Frank , Hippler Michael 
Published: January 2022

ABSTRACTEscherichia coli is a facultative anaerobe that can grow in a variety of environmental conditions. In the complete absence of O2, E. coli can perform a mixed-acid fermentation that contains within it an elaborate metabolism of formic acid. In this study, we use cavity-enhanced Raman spectroscopy (CERS), FTIR, liquid Raman spectroscopy, isotopic labelling, and molecular genetics to make advances in the understanding of bacterial formate and H2 metabolism. It is shown that, under anaerobic (anoxic) conditions, formic acid is generated endogenously, excreted briefly from the cell, and then taken up again to be disproportionated to H2 and CO2 by formate hydrogenlyase (FHL-1). However, exogenously added D-labelled formate behaves quite differently from the endogenous formate and is taken up immediately, independently, and possibly by a different mechanism, by the cell and converted to H2 and CO2. Our data support an anion-proton symport model for formic acid transport. In addition, when E. coli was grown in a micro-aerobic (micro-oxic) environment it was possible to analyse aspects of formate and O2 respiration occurring alongside anaerobic metabolism. While cells growing under micro-aerobic conditions generated endogenous formic acid, no H2 was produced. However, addition of exogenous formate at the outset of cell growth did induce FHL-1 biosynthesis and resulted in formate-dependent H2 production in the presence of O2.
Structural insights as to how iron-loaded siderophores are imported into Mycobacterium tuberculosis by IrtAB
Authors: Sun Shan , Gao Yan , Yang Xiaolin , Yang Xiuna , Hu Tianyu , Liang Jingxi , Xiong Zhiqi , Ren Pengxuan , Bai Fang , Guddat Luke W. , Yang Haitao , Rao Zihe , Zhang Bing 
Published: January 2022

AbstractThe ATP-binding cassette (ABC) transporter, IrtAB, plays a vital role in the replication and viability of Mycobacterium tuberculosis (Mtb), where its function is to import iron-loaded siderophores. Unusually, it adopts the typical fold of canonical ABC exporters. Here, we report the structure of unliganded Mtb IrtAB and its structure in complex with ATP, ADP, and an ATP analogue (AMP-PNP) at resolutions from 2.9 to 3.5 Å. In the ATP-bound state, the two nucleotide-binding domains (NBDs) form a “head-to-tail” dimer, but IrtAB has an unexpectedly occluded conformation, with the inner core forming a large hydrophilic cavity of about 4600 Å3. Comparison of the structure of the transporter in inward-facing and occluded conformations reveals that the NBD and the intracellular helical region of transmembrane domain (TMD) have an asymmetric allosteric mechanism when ATP binding/hydrolysis such that the one exhibits rigid-body rotation and the other moves in a concerted response as a rigid body. This study provides a molecular basis for the ATP-driven conformational changes that occur in IrtAB and an explanation as to how iron-loaded siderophores are imported into Mtb by IrtAB.
Quantitative Isothermal Amplification on Paper Membranes using Amplification Nucleation Site Analysis
Authors: Sullivan Benjamin P. , Chou Yu-Shan , Bender Andrew T. , Martin Coleman D. , Kaputa Zoe G. , March Hugh , Song Minyung , Posner Jonathan D. 
Published: January 2022

AbstractQuantitative nucleic acid amplification tests (qNAATs) are critical in treating infectious diseases, such as in HIV viral load monitoring or SARS-CoV-2 testing, in which viral load indicates viral suppression or infectivity. Quantitative PCR is the gold standard tool for qNAATs; however, there is a need to develop point-of-care (POC) qNAATs to manage infectious diseases in outpatient clinics, low- and middle-income countries, and the home. Isothermal amplification methods are an emerging tool for POC NAATs as an alternative to traditional PCR-based workflows. Previous works have focused on relating isothermal amplification bulk fluorescence signals to input copies of target nucleic acids for sample quantification with limited success. In this work, we show that recombinase polymerase amplification (RPA) reactions on paper membranes exhibit discrete fluorescent amplification nucleation sites. We demonstrate that the number of nucleation sites can be used to quantify HIV-1 DNA and RNA in less than 20 minutes. An image-analysis algorithm quantifies nucleation sites and determines the input nucleic acid copies in the range of 67-3,000 copies per reaction. We demonstrate a mobile phone-based system for image capture and onboard processing, illustrating that this method may be used at the point-of-care for qNAATs with minimal instrumentation.
SLC38A2 provides proline to fulfil unique synthetic demands arising during osteoblast differentiation and bone formation
Authors: Shen Leyao , Yu Yilin , Zhou Yunji , Pruett-Miller Shondra M. , Zhang Guo-Fang , Karner Courtney M. 
Published: January 2022

AbstractCellular differentiation is associated with the acquisition of a unique protein signature which is essential to attain the ultimate cellular function and activity of the differentiated cell. This is predicted to result in unique biosynthetic demands that arise during differentiation. Using a bioinformatic approach, we discovered osteoblast differentiation is associated with increased demand for the amino acid proline. When compared to other differentiated cells, osteoblast-associated proteins including RUNX2, OSX, OCN and COL1A1 are significantly enriched in proline. Using a genetic and metabolomic approach, we demonstrate that the neutral amino acid transporter SLC38A2 acts cell autonomously to provide proline to facilitate the efficient synthesis of proline-rich osteoblast proteins. Genetic ablation of SLC38A2 in osteoblasts limits both osteoblast differentiation and bone formation in mice. Mechanistically, proline is primarily incorporated into nascent protein with little metabolism observed. Collectively, these data highlight a requirement for proline in fulfilling the unique biosynthetic requirements that arise during osteoblast differentiation and bone formation.
Ontogenetic Color Switching in Lizards as a by-Product of Guanine Cell Development
Authors: Zhang Gan , Yallapragada Venkata Jayasurya , Shemesh Michal , Wagner Avital , Upcher Alexander , Pinkas Iddo , McClelland Harry L.O. , Hawlena Dror , Palmer Benjamin A. 
Published: January 2022

AbstractMany animals undergo dramatic changes in colour during development1,2. Changes in predation risk during ontogeny are associated with spectacular switches in defensive colours, typically involving the replacement of skin or the production of new pigment cells3. Ontogenetic colour systems are ideal models for understanding the evolution and formation mechanisms of animal colour which remain largely enigmatic2. We show that defensive colour switching in lizards arises by reorganization of a single photonic system, as an incidental by-product of chromatophore maturation. The defensive blue tail colour of hatchling A. beershebensis lizards is produced by light scattering from premature guanine crystals in underdeveloped iridophore cells. Camouflaged adult tail colours emerge upon reorganization of the guanine crystals into a photonic reflector during chromatophore maturation. The substituent guanine crystals form by the attachment of individual nanoscopic plates, which coalesce during growth to form single crystals. Our results show that the blue colour of hatchlings is a fortuitous, but necessary, precursor to the development of adult colour. Striking functional colours in animals can thus arise not as distinct evolutionary innovations but via exploitation of the timing of naturally occurring changes in chromatophore cell development.
Pericentrin is a Kinesin-1 Activator that Drives Centriole Motility
Authors: Hannaford Matthew R. , Liu Rong , Billington Neil , Swider Zachary T. , Galletta Brian J. , Fagerstrom Carey J. , Combs Christian , Sellers James R. , Rusan Nasser M. 
Published: January 2022

AbstractCentrosome positioning is essential for their function. Typically, centrosomes are transported to various cellular locations through the interaction of centrosome nucleated microtubules with motor proteins. However, it remains unknown how centrioles migrate in cellular contexts in which centrioles do not nucleate microtubules. Here, we demonstrate that during interphase inactive centrioles move directly along the non-centrosomal microtubule network as cargo for the motor protein Kinesin-1. We identify Pericentrin-Like-Protein (PLP) as a novel Kinesin-1 interacting molecule essential for centriole motility. PLP directly interacts with the cargo binding domain of Kinesin-1 and they comigrate on microtubules in vitro. Finally, we demonstrate that PLP-Kinesin-1 dependent transport is essential for centrosome asymmetry age-dependent centrosome inheritance in asymmetric stem cell division.
Considerations associated with synchronous and asynchronous video use in online learning
Authors: Cohen Jay Andrew 
Published: January 2022

Purpose
A substantial amount of the heavy lifting associated with getting face-to-face courses online as part of the emergency remote teaching response to the global COVID-19 pandemic has fallen, at times rather awkwardly at the feet of teachers and trainers. Teachers and trainers have had to become both learning designers, and online tutors overnight. In many instances what we have seen as part of this pivoting to online learning is the perpetuation of existing classroom based pedagogical approaches. This has, in most instances equated to the delivery of live lectures via video-conferencing software (such as Zoom and Skype), or previously recorded classroom-based lectures being reused.

Design/methodology/approach
This paper explores the affordances of synchronous and asynchronous lecture video use in online learning based on the view that whilst pre-recorded videos are customary and can add added value to the online learning environment, they should be used based pedagogical pertinence, rather than through convenience or simply to save time.

Findings
The pedagogical nuances of online learning and student engagement must be broadly considered, so that the formation of conditions in which learning is most likely is at the forefront.

Originality/value
This is a viewpoint paper. Much of the paper is based on the views of the author – supported by references/research.
Patent management: the prominent role of strategy and organization
Authors: Agostini Lara , Nosella Anna , Holgersson Marcus 
Published: January 2022

PurposeThe purpose of this article is twofold; to verify the existence of different profiles of firms based on the level of sophistication of their patent management core processes and to test the impact of the interplay between two patent management supporting dimensions, namely patent strategy and organization for patenting, on the level of sophistication of patent management core processes.Design/methodology/approachThe method consists of a survey study, collecting data from a set of European patent management professionals. These data are analyzed with factor analysis, cluster analysis and regression analysis to test several hypotheses.FindingsThe results show that patent strategy positively and significantly impacts patent management sophistication, and that the patent organization positively moderates this relationship. In other words, a patent strategy, supported by a well-developed patent organization and culture, will positively influence the processes of managing a firm's patent portfolio.Originality/valueThis study is, to the authors’ knowledge, the first one to provide quantitative evidence that supports the notion that it is important to take a strategic and organizational perspective of patent management.
Salesperson moral identity and value co-creation
Authors: Itani Omar S. , Chonko Larry , Agnihotri Raj 
Published: January 2022

Purpose
The purpose of this study is to examine the role of salesperson moral identity centrality in value co-creation. This study identified and tested an extended identity-based formation process of selling orientation, customer orientation and value co-creation. This was accomplished by examining the role of inclusion of others in the self and circle of moral regard in the mechanism through which moral identity centrality impacts selling orientation, customer orientation and value co-creation, taking into account the contingency role of salesperson self-construal.

Design/methodology/approach
An extended identity-behavior model grounded in identity theory and the social-cognitive perspective of moral identity centrality was tested. The study used survey data from business-to-business salespeople. Data collected was analyzed using structural equation modeling.

Findings
The results show that a central moral identity to a salesperson’s self-drives higher expansion of the salesperson’s circle of moral regard. This process facilitates the mechanisms for salesperson moral identity centrality to decrease selling orientation and increase customer orientation and value co-creation, leading to higher sales performance. Independent self-construal is found to deteriorate the positive effects of salesperson moral identity centrality on the inclusion of others in the self, expansion of the circle of moral regard and customer orientation.

Research limitations/implications
Through the conceptualized and tested framework, the study opens the door for additional research to inspect the role of moral identity centrality in sales.

Practical implications
Findings have implications for the human resource side of sales organizations in the areas of recruitment, mentoring, coaching and training. Moral identity centrality plays a vital role in the interface between salespeople and customers, leading to improved behavioral and sales outcomes. Sales managers must look for their salespeople’s moral identity centrality to improve morality in the attitudes and decision-making of their salesforce.

Originality/value
To the best of the authors’ knowledge, this study is the first to uncover the vital impacts of salesperson moral identity centrality on selling orientation, customer orientation and value co-creation. Through the conceptualized and tested framework, the study opens the door for additional research to inspect the role of moral identity centrality in sales.
Fuzzy-based metaheuristic algorithm for optimization of fuzzy controller: fault-tolerant control application
Authors: Patel Himanshukumar Rajendrabhai 
Published: January 2022

PurposeFuzzy-based metaheuristic algorithm is used to optimize the fuzzy controllers for the nonlinear level control system subject to uncertainty specially in the main actuator that has lost effectiveness (LOE). To optimize the fuzzy controller, type-1 harmonic search (HS) and interval type-2 (HS) will be used.Design/methodology/approachThe type-1 and type-2 fuzzy-based HS algorithms are designed for optimization of fuzzy controllers for Fault-Tolerant Control (FTC) applications, and this research proposes a fuzzy-based HS metaheuristic method. The performance of a fuzzy logic-based HS algorithm applied to a nonlinear two-tank level control process with a main actuator that has lost effectiveness (LOE) and also the same controller will be tested on DC motor angular position control with and without noise.FindingsThe key contribution of this work is the discovery of the best approach for generating an optimal vector of values for the fuzzy controller's membership function optimization. This is done in order to improve the controller's performance, bringing the process value of the two-tank level control process closer to the target process value (set point). It is worth noting that the type-1 fuzzy controller that has been optimized is an interval type-2 fuzzy system, which can handle more uncertainty than a type-1 fuzzy system.Originality/valueThe type-1 and type-2 fuzzy-based HS algorithms are designed for optimization of fuzzy controllers for FTC applications, and this research proposes a fuzzy-based HS metaheuristic method. The performance of a fuzzy logic-based HS algorithm applied to a nonlinear two-tank level control process with a main actuator that has LOE will be tested on DC motor angular position control with noise. Two nonlinear uncertain processes are used to demonstrate the effectiveness of the proposed control scheme.
Design and implementation of energy-aware cross-layer routing protocol for wearable body area network
Authors: Vadlamudi Muniraju Naidu , M.D. Asdaque Hussain 
Published: January 2022

Purpose
A wireless body area network (WBAN) plays a crucial role in the health-care domain. With the emergence of technologies like the internet of things, there is increased usage of WBAN for providing quality health services. With wearable devices and sensors associated with human body, patient’s vital signs are captured and sent to doctor. The WBAN has number of sensor nodes that are resource constrained. The communications among the nodes are very crucial as human health information is exchanged. The purpose of this paper aims to have Quality of Service (QoS) with energy aware and control overhead aware. Maximizing network lifetime is also essential for the improved quality in services. There are many existing studies on QoS communications in WBAN.

Design/methodology/approach
In this paper, with the aim of energy-efficient WBAN for QoS, a cross-layer routing protocol is designed and implemented. A cross-layer routing protocol that is ad hoc on-demand distance vector (AODV)-based, energy and control overhead-aware (AODV-ECOA) is designed and implemented for energy-efficient routing in WBAN. The cross-layer design that involves multiple layers of open systems interconnection reference model, which will improve energy efficiency and thus QoS.

Findings
Implementation is simulated using the network simulator tool, i.e. NS-2. The proposed cross-layer routing protocol AODV-ECOA shows least bandwidth requirement by control packets, leading to less control overhead, highest packet delivery ratio and energy efficiency. The experimental results revealed that AODV-ECOA shows better performance over existing protocols such as AODV and POLITIC.

Originality/value
An efficient control overhead reduction algorithm is proposed for reducing energy consumption further and improves performance of WBAN communications to realize desired QoS.
That old saying about wine and age: identifying South African age-cohort preferences
Authors: Kruger Martinette , Viljoen Adam 
Published: January 2022

Purpose
This study aims to identify the preferences of wine consumers based on age cohorts to identify differences in consumption from a developing country perspective, with a predominantly younger population, to determine wine consumption longevity.

Design/methodology/approach
The target population was wine consumers in South Africa. Through convenience sampling, the data were collected in 2020 via a self-administered online questionnaire. In total, 20,997 fully completed the questionnaire. The age categories of the respondents were assigned to a particular age cohort to differentiate the market.

Findings
The age cohorts revealed five cohorts, namely, Gen Z: 18–24 years (11%); Young Gen Y: 25–34 years (32%); Mature Gen Y: 35–44 years (25%); Gen X: 45–54 years (17%); and Baby boomers: 55+ years (15%). Segmenting South African wine consumers based on their age cohorts revealed statistically significant differences based on their socio-demographics, wine preferences and consumption behavior. A typology of domestic wine consumers is consequently proposed: basic, budget conscious and image-oriented wine drinking Gen Z’s; experimenting and enjoyment-oriented wine drinking Young Gen Y-ers; aspirational and purposive wine drinking Mature Gen Y-ers; ritual-oriented, avid and conspicuous wine drinking Gen X-ers; and conservative, value-seeking and experienced wine drinking Baby Boomers.

Practical implications
This knowledge has important marketing implications and can create a greater appreciation for South African wines among the different age cohorts. The research shows the value of the generational theory in understanding wine consumers’ consumption and highlights the importance of analyzing different generations rather than solely focusing on one, as this could lead to mismanagement of resources.

Originality/value
This is one of the most comprehensive national surveys aimed at the South African wine consumer. The research fills the current literature gap regarding the characteristics of the different age cohorts and shows how wine consumption and preferences may change over time.