bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deconstructing the Cortical Sources of Frequency Following Responses to Speech: A Cross-species Approach
Authors: Gnanateja G. Nike , Rupp Kyle , Llanos Fernando , Remick Madison , Pernia Marianny , Sadagopan Srivatsun , Teichert Tobias , Abel Taylor J. , Chandrasekaran Bharath 
Published: May 2021

AbstractTime-varying pitch is a vital cue for human speech perception. Neural processing of time-varying pitch has been extensively assayed using scalp-recorded frequency-following responses (FFRs), an electrophysiological signal thought to reflect integrated phase-locked neural ensemble activity from subcortical auditory areas. Emerging evidence increasingly points to a putative contribution of auditory cortical ensembles to the scalp-recorded FFRs. However, the properties of cortical FFRs and precise characterization of laminar sources are still unclear. Here we used direct human intracortical recordings as well as extra- and intracranial recordings from macaques and guinea pigs to characterize the properties of cortical sources of FFRs to time-varying pitch patterns. We found robust FFRs in the auditory cortex across all species. We leveraged representational similarity analysis as a translational bridge to characterize similarities between the human and animal models. Laminar recordings in animal models showed FFRs emerging primarily from the thalamorecepient layers of the auditory cortex. FFRs arising from these cortical sources significantly contributed to the scalp-recorded FFRs via volume conduction. Our research paves the way for a wide array of studies to investigate the role of cortical FFRs in auditory perception and plasticity.Significance StatementFrequency following responses (FFRs) to speech are scalp-recorded neural signals that inform the fidelity of sound encoding in the auditory system. FFRs, long believed to arise from brainstem and midbrain, have shaped our understanding of sub-cortical auditory processing and plasticity. Non-invasive studies have shown cortical contributions to the FFRs, however, this is still actively debated. Here we employed direct cortical recordings to trace the cortical contribution to the FFRs and characterize the properties of these cortical FFRs. With extra-cranial and intra-cranial recordings within the same subjects we show that cortical FFRs indeed contribute to the scalp-recorded FFRs, and their response properties differ from the sub-cortical FFRs. The findings provide strong evidence to revisit and reframe the FFR driven theories and models of sub-cortical auditory processing and plasticity with careful characterization of cortical and sub-cortical components in the scalp-recorded FFRs.
Interleukin-6 mediates PSAT1 expression and serine metabolism in TSC2-deficient cells
Authors: Wang Ji , Filippakis Harilaos , Hougard Thomas , Du Heng , Ye Chenyang , Liu Heng-Jia , Zhang Long , Hindi Khadijah , Bagwe Shefali , Nijmeh Julie , Asara John M. , Shi Wei , El-Chemaly Souheil , Henske Elizabeth P. , Lam Hilaire C. 
Published: May 2021

AbstractTuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM) are caused by aberrant mechanistic Target of Rapamycin Complex 1 (mTORC1) activation due to loss of either TSC1 or TSC2. Cytokine profiling of TSC2-deficient LAM patient-derived cells revealed striking upregulation of Interleukin-6 (IL-6). LAM patient plasma contained increased circulating IL-6 compared with healthy controls, and TSC2-deficient cells showed upregulation of IL-6 transcription and secretion compared to wildtype cells. IL-6 blockade repressed the proliferation and migration of TSC2-deficient cells and reduced oxygen consumption and extracellular acidification. U-13C glucose tracing revealed that IL-6 knockout reduced 3-phosphoserine and serine production in TSC2-deficient cells, implicating IL-6 in de novo serine metabolism. IL-6 knockout reduced expression of phosphoserine aminotransferase 1 (PSAT1), an essential enzyme in serine biosynthesis. Importantly, recombinant IL-6 treatment rescued PSAT1 expression in the TSC2-deficient, IL-6 knockout clones selectively and had no effect on wildtype cells. Treatment with anti-IL-6 (aIL-6) antibody similarly reduced cell proliferation and migration and reduced renal tumors in Tsc2+/- mice, while reducing PSAT1 expression. These data reveal a novel mechanism through which IL-6 regulates serine biosynthesis, with potential relevance to the therapy of tumors with mTORC1 hyperactivity.ClassificationMajor category: Biological Sciences Minor category: Cell Biology
Bexarotene derivatives modify responses in acute myeloid leukemia
Authors: Hadwiger Gayla , di Martino Orsola , Ferris Margaret A. , Vu Anh , Frederick Thomas E. , Bowman Gregory R. , Ruminski Peter , Wagner Carl , Welch John S. 
Published: May 2021

AbstractThe retinoids all-trans retinoic acid (ATRA) and bexarotene are active in acute myeloid leukemia (AML), but responses beyond acute promyelocytic leukemia (APL) have been more modest than APL responses. To determine whether chemical modification of bexarotene might augment retinoid responses in AML, we screened a series of 38 bexarotene derivatives for activity in a mouse MLL-AF9 leukemia cell line, which exhibits strong synergistic sensitivity to the combination of ATRA and bexarotene. We found that RXRA potency correlated with anti-leukemic activity and that only one compound (103-4) with dual RARA/RXRA activity was capable of ATRA-independent anti-leukemic activity. We evaluated bioisostere and cyclohexane modifications for potential resistance to P450 metabolism and found that bioisosteres reduced potency and that bezopyran, cyclopentane, and cyclohexene modifications only modestly reduced susceptibility to metabolism. Collectively, these studies provide a map of the structure-activity relationships of bexarotene with outcomes related to RXRA and RARA activity, corepressor binding, compound stability, and anti-leukemic potential.
Viability of MS2 and Phi6 Bacteriophages on Carpet and Dust
Authors: Nastasi Nicholas , Renninger Nicole , Bope Ashleigh , Cochran Samuel J. , Greaves Justin , Haines Sarah R. , Balasubrahmaniam Neeraja , Stuart Katelyn , Panescu Jenny , Bibby Kyle , Hull Natalie M. , Dannemiller Karen C. 
Published: May 2021

AbstractRespiratory viral illnesses are commonly spread in the indoor environment through multiple transmission routes, including droplets, aerosols, and direct/indirect contact. Indoors, resuspension of dust from flooring is a major source of human exposure. However, it is critical to determine viral persistence on dust and flooring to better characterize human exposure. The goal of this work is to determine viral viability on two carpet types (cut and looped) and house dust over time and after four different cleaning methods. MS2 and Phi6 bacteriophages were used to represent non-enveloped and enveloped viruses, respectively. These viral surrogates were placed in an artificial saliva solution and nebulized onto carpet or dust. Viability was measured at various time points (0, 1, 2, 3, 4, 24, and 48 hours) and after cleaning (vacuuming, hot water extraction with stain remover, steam, and a disinfection spray). Viability decay was modeled as first-order. MS2 bacteriophages showed slower viability decay rates in dust (−0.11 hr-1), cut carpet (−0.20 hr-1), and looped carpet (−0.09 hr-1) compared to Phi6 (−3.36 hr-1, -1.57 hr-1, and - 0.20 hr-1respectively). The difference between phages was statistically significant in dust and cut carpet (p<0.05). Viral RNA demonstrated minimal degradation that in most cases was not statistically different from zero over the 48 hours measured (p>0.05). Viable viral concentrations were reduced to below the detection limit for steam and disinfection for both MS2 and Phi6 (p<0.05), while vacuuming and hot water extraction with stain remover showed no significant changes in concentration from uncleaned carpet (p>0.05). This study used viral surrogates and did not model risk of viral transmission via dust. Overall, these results demonstrate that MS2 and Phi6 bacteriophages can remain viable in carpet and dust for several hours to days, and cleaning techniques with heat and disinfectants may be more effective than standard vacuuming for viral removal. Future work should model risk from exposure via dust and flooring for various viruses such as influenza, SARS-CoV-2, and RSV.Abstract Figure
Targeted redesign of suramin analogs for novel antimicrobial lead development
Authors: Dey Debayan , Ramakumar Suryanarayanarao , Conn Graeme L. 
Published: May 2021

ABSTRACTThe emergence of new viral infections and drug resistant bacteria urgently necessitates expedient therapeutic development. Repurposing and redesign of existing drugs against different targets is one potential way in which to accelerate this process. Suramin was initially developed as a successful anti-parasitic drug but has also shown promising antiviral and antibacterial activities. However, due to its high conformational flexibility and negative charge, suramin is considered quite promiscuous towards positively charged sites within nucleic acid binding proteins. Although some suramin analogs have been developed against specific targets, only limited structure activity relationship (SAR) studies were performed, and virtual screening has yet to be used to identify more specific inhibitor(s) based on its scaffold. Using available structures, we investigated suramin’s target diversity, confirming that suramin preferentially binds to protein pockets which are both positively charged and enriched in aromatic or leucine residues. Further, suramin’s high conformational flexibility allows adaptation to structurally diverse binding surfaces. From this platform, we developed a framework for structure- and docking-guided elaboration of suramin analog scaffolds using virtual screening of suramin and heparin analogs against a panel of diverse therapeutically relevant viral and bacterial protein targets. Use of this new framework to design potentially specific suramin analogs is exemplified using the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and nucleocapsid protein, identifying leads that might inhibit a wide range of coronaviruses. The approach presented here establishes a computational framework for designing suramin analogs against different bacterial and viral targets and repurposing existing drugs for more specific inhibitory activity.For Table of Contents Use OnlyTable of Contents Graphic
Plastic mulches reduce adult and larval populations ofDrosophila suzukiiin fall-bearing raspberry
Authors: McIntosh Hanna , Atucha Amaya , Townsend Philip A , Hills W Beckett , Guédot Christelle 
Published: May 2021

AbstractThe invasive spotted-wing drosophila,Drosophila suzukii, is a major pest of fruit crops world-wide. Management ofD. suzukiirelies heavily on chemical control in both organic and conventional systems, and there is a need to develop more sustainable management practices. We evaluated the efficacy of three colors of plastic mulches at reducing populations ofD. suzukiiin fall-bearing raspberry and assessed the mulches’ impacts on canopy microclimate factors relevant toD. suzukii. Black, white, and metallic plastic mulches reduced adultD. suzukiipopulations by 42-51% and larval populations by 52-72% compared to the grower standard. The mulches did not change canopy temperature or relative humidity, but metallic mulches increased canopy light intensity compared to the black mulch. Radiance in the visible spectrum (401-680 nm) was higher for the white and metallic mulch plots, but the black mulch plots did not differ from the control. In the UV spectrum (380-400 nm), all three plastic mulches had higher radiance than the control plots. Future studies will determine whether changes in radiance are associated with the observed reduction inD. suzukiipopulations. Plastic mulches are a promising cultural practice for managingD. suzukiisince they can reduce adult and larval populations and could be incorporated into an integrated pest management program in both organic and conventional systems.
Sequence Determinants of Human Junctophilin-2 Protein Nuclear Localization and Phase Separation
Authors: Guo Ang , Fang Wenjuan , Gibson Savannah 
Published: May 2021

AbstractJunctophilin-2 (JPH2) was conventionally considered as a structural membrane binding protein. Recently, it was shown that proteolytically truncated mouse JPH2 variants are imported into nucleus to exert alternative functions. However, the intranuclear behaviors of human JPH2 (hJPH2) and underlying molecular determinants have not been explored. Here, we demonstrate that full-length hJPH2 is imported into nucleus in human cells by two nuclear localization signals (NLSs), including a newly discovered one at the C-terminus. Importantly, unlike the JPH2 N-terminal truncation which diffuses throughout the nucleus, full-length hJPH2 forms nuclear bodies behaving like liquid-liquid phase separated droplets that are separated from chromatin. The C-terminal transmembrane domain is required for the formation of hJPH2 droplets. Oxidation mimicking substitution of residues C678 and M679 augments the formation of hJPH2 nuclear droplets, suggesting nuclear hJPH2 liquid-liquid phase separation could be modulated by oxidative stress. Mutation A405D, which introduces a negatively charged residue into an intrinsic disordered region (IDR) of hJPH2, turns liquid-like droplets into amyloid-like aggregates. Depletion of an Alanine Rich Region in the IDR recapitulates the liquid-amyloid phase transition. The MORN repeat regions of hJPH2 encodes intrinsic tendency to form amyloid-like structure. Together, these data for the first time revealed the novel intrinsic properties of hJPH2 to form nuclear liquid droplets, and identified critical functional domains and residues encoding these properties. We propose that hJPH2 droplets could function as membrane-less organelles participating in nuclear regulatory processes.
Categorical edge-based analyses of phylogenomic data reveal conflicting signals for difficult relationships in the avian tree
Authors: Wang Ning , Braun Edward L. , Liang Bin , Cracraft Joel , Smith Stephen A. 
Published: May 2021

ABSTRACTPhylogenetic analyses fail to yield a satisfactory resolution of some relationships in the tree of life even with genome-scale datasets, so the failure is unlikely to reflect limitations in the amount of data. Gene tree conflicts are particularly notable in studies focused on these contentious nodes, and taxon sampling, different analytical methods, and/or data type effects can further confound analyses. Although many efforts have been made to incorporate biological conflicts, few studies have curated individual genes for their efficiency in phylogenomic studies. Here, we conduct an edge-based analysis of Neoavian evolution, examining the phylogenetic efficacy of two recent phylogenomic bird datasets and three datatypes (ultraconserved elements [UCEs], introns, and coding regions). We assess the potential causes for biases in signal-resolution for three difficult nodes: the earliest divergence of Neoaves, the position of the enigmatic Hoatzin (Opisthocomus hoazin), and the position of owls (Strigiformes). We observed extensive conflict among genes for all data types and datasets even after meticulous curation. Edge-based analyses (EBA) increased congruence and provided information about the impact of data type, GC content variation (GCCV), and outlier genes on each of nodes we examined. First, outlier gene signals appeared to drive different patterns of support for the relationships among the earliest diverging Neoaves. Second, the placement of Hoatzin was highly variable, although our EBA did reveal a previously unappreciated data type effect with an impact on its position. It also revealed that the resolution with the most support here was Hoatzin + shorebirds. Finally, GCCV, rather than data type (i.e., coding vs non-coding)per se, was correlated with a signal that supports monophyly of owls + Accipitriformes (hawks, eagles, and New World vultures). Eliminating high GCCV loci increased the signal for owls + mousebirds. Categorical EBA was able to reveal the nature of each edge and provide a way to highlight especially problematic branches that warrant a further examination. The current study increases our understanding about the contentious parts of the avian tree, which show even greater conflicts than appreciated previously.
The effect of knowledge type and culture on arts audiences’ propensity for experience-sharing
Authors: Chieffi Verdiana , Pichierri Marco , Peluso Alessandro M. , Collu Cristiana , Guido Gianluigi 
Published: May 2021

PurposeThis study examines the effect of both objective knowledge (i.e., what arts audience members actually know about art) and subjective knowledge (i.e., what arts audiences members think they know about art) on their propensity for experience-sharing (i.e., the tendency to share art-related experiences with other individuals). In addition, the study examines the role of culture (i.e., whether arts audiences belong to an individualistic or collectivistic culture) on the above-mentioned relationship.Design/methodology/approachData were gathered through a field survey at a large contemporary art museum in Italy, conducted via a structured questionnaire and analyzed using multiple regression analysis.FindingsResults indicate that both subjective and objective knowledge positively affect arts audiences’ propensity for experience-sharing, such as talking to others about a visit to an art gallery. Moreover, such effects appear to vary depending on culture: objective knowledge seems to positively influence experience-sharing when audiences belong to collectivistic cultures, whereas subjective knowledge seems to positively influence experience-sharing when they belong to individualistic cultures.Practical implicationsThe study’s findings could motivate arts managers to emphasize the implementation of international communication strategies aimed at reinforcing arts audiences’ subjective and objective knowledge since these variables are positively associated with their propensity for experience-sharing with others.Originality/valueThis is the first study to assess the effects of objective and subjective knowledge, alongside the cultural dimensions of individualism and collectivism, on arts audiences’ propensity for experience-sharing.
Students' readiness for e-learning during the COVID-19 pandemic in a South-East Asian university: a Rasch analysis
Authors: Adams Donnie , Chuah Kee Man , Sumintono Bambang , Mohamed Ahmed 
Published: May 2021

PurposeUniversities have shifted from face-to-face learning environments to e-learning in response to the COVID-19 pandemic. However, the sudden change to online teaching has raised concerns among lecturers about students' readiness for e-learning. This study investigates students' readiness for e-learning during the COVID-19 pandemic and specifically assesses any significant differences between students' gender, age, ethnicity, level of education, field of study and their readiness for an e-learning environment.Design/methodology/approachThe study employed a non-experimental quantitative research design. Data were gathered from a sample of 298 undergraduate and 101 postgraduate students. WINSTEPS Rasch model measurement software was used to determine the reliability and validity of the research instrument. Descriptive, inferential statistics and differential item functioning (DIF) test were used to assess students' readiness for an e-learning mode of instruction with the latter specifically analysing students' demographic factors and their readiness for an e-learning environment.FindingsFindings identified that most students are ready for an e-learning mode of instruction. Further analysis indicated that there were differences in students' readiness for e-learning based on their demographic profiles.Research limitations/implicationsThis study provides insights on students' readiness towards e-learning, discusses implications for e-learning practices in higher education institutions during the COVID-19 pandemic and offers recommendations for future research.Originality/valueThis study provides evidences of students' readiness for e-learning in respect to their gender, age, ethnicity, level of education and field of study. This information could help lecturers to reflect on their own teaching practices, adjust their teaching approaches and subsequently, develop appropriate e-learning methods that best suit the student diversity in their classrooms.
Microfoundations of SME open innovation: the role of help, knowledge sharing and hiding
Authors: Aleksić Darija , Rangus Kaja , Slavec Gomezel Alenka 
Published: May 2021

PurposeThe purpose of this research is to better understand the human aspects of open innovation in small- and medium-sized enterprises (SMEs) by exploring how intrinsic and extrinsic motivation influence enjoyment in helping others, knowledge sharing and knowledge hiding and consequently firms' open innovation.Design/methodology/approachWe collected data with a survey among CEOs in 140 SMEs and performed confirmatory factor analysis applying structural equation modeling in IBM SPSS AMOS (v. 26).FindingsResults reveal that intrinsic motivation is positively associated with helping behavior and knowledge sharing and negatively associated with knowledge hiding. We also confirm the positive relationship between extrinsic motivation and knowledge sharing. Moreover, we find that knowledge sharing increases and knowledge hiding decreases the firm-level open innovation. Especially in high-tech industry, knowledge sharing is a vital determinant of open innovation.Originality/valueResponding to the calls for a deeper understanding of the individual-level factors that determine organization-level open innovation, in this research we focus on the human aspect of open innovation in SMEs. Open innovation is a widely recognized and implemented concept among large corporations and facilitates better understanding of new technological and market developments both within and outside of organizations. However, understanding of the microfoundations of open innovation in smaller firms is still limited, but this steam of research is growing rapidly.
From theory to practice: Jewish and Arabs students in academia practice multicultural education
Authors: Masry-Herzallah Asmahan , Amzalag Meital 
Published: May 2021

PurposeThe research examined factors of academic studies as perceived by Jewish and Arab students in Israel, and changes in their implementation of activities in a multicultural context in the field of education, comparing between undergraduates studying for a BA in education and graduate students for MA in education and attending a course titled “Multiculturalism in the Global Era”.Design/methodology/approachThe findings are derived from a questionnaire distributed to Arab and Jewish students (N = 434), studying together in the Faculty of Education of one academic college in Israel. In total, 251 of them were graduate students, and 183 who were undergraduates.FindingsIt was found that insofar as the students from either programme acquired knowledge and tools regarding multiculturalism, they reported (1) more positive attitudes regarding the “Other” group and regarding multiculturalism, (2) implementation of a larger number of activities relating to multiculturalism in the field of education, (3) Arab students performed more activities in multicultural contexts and (4) older students performed a larger number of activities in multicultural contexts. The research findings also indicated a direct relation between participation in the course and activities conducted in the field of education. In addition, students' acquiring of knowledge on multiculturalism mediated the relation between participation in the course and implementation of multicultural activities in the field of education.Originality/valueThe research stresses the importance of higher education institutions in promoting knowledge and practice of multiculturalism in Israeli society.