bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glioblastoma myeloid-derived suppressor cell subsets express differential macrophage migration inhibitory factor receptor profiles that can be targeted to reduce immune suppression
Authors: Alban Tyler J. , Bayik Defne , Otvos Balint , Rabljenovic Anja , Leng Lin , Jia-shiun Leu , Roversi Gustavo , Lauko Adam , Momin Arbaz , Mohammadi Alireza M. , Peereboom David M. , Ahluwalia Manmeet S. , Matsuda Kazuko , Yun Kyuson , Bucala Richard , Vogelbaum Michael A. , Lathia Justin D. 
Published: December 2019

AbstractThe application of tumor immunotherapy to glioblastoma (GBM) is limited by an unprecedented degree of immune suppression due to factors that include high numbers of immune suppressive myeloid cells, the blood brain barrier, and T cell sequestration to the bone marrow. We previously identified an increase in immune suppressive myeloid-derived suppressor cells (MDSCs) in GBM patients, which correlated with poor prognosis and was dependent on macrophage migration inhibitory factor (MIF). Here we examine the MIF signaling axis in detail in murine MDSC models, GBM-educated MDSCs and human GBM. We found that the monocytic subset of MDSCs (M-MDSCs), expressed high levels of the MIF cognate receptor CD74 and was localized in the tumor microenvironment. In contrast, granulocytic MDSCs (G-MDSCs) expressed high levels of the MIF non-cognate receptor CXCR2 and showed minimal accumulation in the tumor microenvironment. Furthermore, targeting M-MDSCs with ibudilast, a brain penetrant MIF-CD74 interaction inhibitor, reduced MDSC function and enhanced CD8 T cell activity in the tumor microenvironment. These findings demonstrate the MDSC subsets differentially express MIF receptors and may be leveraged for specific MDSC targeting.
Theta activity paradoxically boosts gamma and ripple frequency sensitivity in prefrontal interneurons
Authors: Merino Ricardo Martins , Leon-Pinzon Carolina , Stühmer Walter , Möck Martin , Staiger Jochen F. , Wolf Fred , Neef Andreas 
Published: December 2019

AbstractFast oscillations in cortical circuits critically depend on GABAergic interneurons. Which interneuron types and populations can drive different cortical rhythms, however, remains unresolved and may depend on brain state. Here, we measured the sensitivity of different GABAergic interneurons in prefrontal cortex under conditions mimicking distinct brain states. While fast-spiking neurons always exhibited a wide bandwidth of around 400 Hz, the response properties of spike-frequency adapting interneurons switched with the background input’s statistics. Slowly fluctuating background activity, as typical for sleep or quiet wakefulness, dramatically boosted the neurons’ sensitivity to gamma- and ripple-frequencies. A novel time-resolved dynamic gain analysis revealed rapid sensitivity modulations that enable neurons to periodically boost gamma oscillations and ripples during specific phases of ongoing low-frequency oscillations. This mechanism presumably contributes substantially to cross-frequency coupling and predicts these prefrontal interneurons to be exquisitely sensitive to high-frequency ripples, especially during brain states characterized by slow rhythms.
Inter-domain dynamics in the chaperone SurA and multi-site binding to its unfolded outer membrane protein clients
Authors: Calabrese Antonio N. , Schiffrin Bob , Watson Matthew , Karamanos Theodoros K. , Walko Martin , Humes Julia R. , Horne Jim E. , White Paul , Wilson Andrew J. , Kalli Antreas C. , Tuma Roman , Ashcroft Alison E. , Brockwell David J. , Radford Sheena E. 
Published: December 2019

AbstractThe periplasmic chaperone SurA plays a key role in outer membrane protein (OMP) biogenesis.E. coliSurA comprises a core domain and two peptidylprolyl isomerase domains (P1 and P2), but how it binds its OMP clients and the mechanism(s) of its chaperone action remain unclear. Here, we have used chemical cross-linking, hydrogen-deuterium exchange, single-molecule FRET and molecular dynamics simulations to map the client binding site(s) on SurA and to interrogate the role of conformational dynamics of the chaperone’s domains in OMP recognition. We demonstrate that SurA samples a broad array of conformations in solution in which P2 primarily lies closer to the core/P1 domains than suggested by its crystal structure. Multiple binding sites for OMPs are located primarily in the core domain, with binding of the unfolded OMP resulting in conformational changes between the core/P1 domains. Together, the results portray a model in which unfolded OMP substrates bind in a cradle formed between the SurA domains, with structural flexibility between its domains assisting OMP recognition, binding and release.
The R2TP chaperone assembles cellular machineries in intestinal CBC stem cells and progenitors
Authors: Maurizy Chloé , Abeza Claire , Pinet Valérie , Ferrand Marina , Paul Conception , Bremond Julie , Langa Francina , Gerbe François , Jay Philippe , Verheggen Céline , Tinari Nicola , Helmlinger Dominique , Lattanzio Rossano , Bertrand Edouard , Hahne Michael , Pradet-Balade Bérengère 
Published: December 2019

SummaryThe R2TP chaperone cooperates with HSP90 to integrate newly synthesized proteins into multi-subunit complexes, yet its role in tissue homeostasis is unknown. Here, we generated conditional, inducible knock-out mice forRpap3to inactivate this core component of R2TP in the intestinal epithelium. In adult mice,Rpap3invalidation caused destruction of the small intestinal epithelium, and death within 10 days. Levels of R2TP substrates were decreased, with strong effects on mTOR, ATM and ATR.Rpap3-deficient CBC stem cells and progenitors also failed to import RNA polymerase II in the nucleus. This correlated with p53 activation, cell cycle arrest and apoptosis. Interestingly, post-mitotic, differentiated cells did not display any of those alterations, indicating that R2TP clients are built in actively proliferating cells. Analyses of tissues from colorectal cancer patients revealed that high RPAP3 levels correlate with bad cancer prognosis. Thus, in the intestine, the R2TP chaperone functions in physiologic and pathologic proliferation.
Estimating the quality of eukaryotic genomes recovered from metagenomic analysis
Authors: Saary Paul , Mitchell Alex L. , Finn Robert D. 
Published: December 2019

AbstractEukaryotes make up a large fraction of microbial biodiversity. However, the field of metagenomics has been heavily biased towards the study of just the prokaryotic fraction. This focus has driven the necessary methodological developments to enable the recovery of prokaryotic genomes from metagenomes, which has reliably yielded genomes from thousands of novel species. More recently, microbial eukaryotes have gained more attention, but there is yet to be a parallel explosion in the number of eukaryotic genomes recovered from metagenomic samples. One of the current deficiencies is the lack of a universally applicable and reliable tool for the estimation of eukaryote genome quality. To address this need, we have developed EukCC, a tool for estimating the quality of eukaryotic genomes based on the dynamic selection of single copy marker gene sets, with the aim of applying it to metagenomics datasets. We demonstrate that our method outperforms current genome quality estimators and have applied EukCC to datasets from two different biomes to enable the identification of novel genomes, including a eukaryote found on the human skin and aBathycoccusspecies obtained from a marine sample.
Social reprogramming in ants induces longevity-associated glia remodeling
Authors: Sheng Lihong , Shields Emily J. , Gospocic Janko , Glastad Karl M. , Ratchasanmuang Puttachai , Raj Arjun , Little Shawn , Bonasio Roberto 
Published: December 2019

ABSTRACTHealthy brain aging is of crucial societal importance; however, the mechanisms that regulate it are largely unknown. Social insects are an outstanding model to study the impact of environment and epigenetics on brain function and aging because workers and queens arise from the same genome but display profound differences in behavior and longevity. InHarpegnathos saltatorants, adult workers can transition to a queen-like phenotypic state called gamergate. This caste transition results in reprogramming of social behavior and lifespan extension. Whether these changes in brain function and physiology cause brain remodeling at the cellular level is not known. Using single-cell RNA-sequencing ofHarpegnathosbrains undergoing caste transition, we uncovered shifts in neuronal and glial populations. In particular, the conversion of workers into long-lived gamergates caused the expansion of ensheathing glia, which maintain brain health by phagocytosing damaged neuronal structures. These glia cells were lost during aging in normal workers but not in longer-lived gamergates. We observed similar caste- and age-associated differences in ensheathing glia in other Hymenoptera as well asDrosophila melanogaster. We propose that enhanced glia-based neuroprotection promotes healthy brain aging and contributes to the extended lifespan of the reproductive caste in social insects.
High Gamma Cortical Processing of Continuous Speech in Younger and Older Listeners
Authors: Kulasingham Joshua P. , Brodbeck Christian , Presacco Alessandro , Kuchinsky Stefanie E. , Anderson Samira , Simon Jonathan Z. 
Published: December 2019

AbstractNeural processing along the ascending auditory pathway is often associated with a progressive reduction in characteristic processing rates. For instance, the well-known frequency-following response (FFR) of the auditory midbrain, as measured with electroencephalography (EEG), is dominated by frequencies from ∼100 Hz to several hundred Hz, phase-locking to the acoustic stimulus at those frequencies. In contrast, cortical responses, whether measured by EEG or magnetoencephalography (MEG), are typically characterized by frequencies of a few Hz to a few tens of Hz, time-locking to acoustic envelope features. In this study we investigated a crossover case, cortically generated responses time-locked to continuous speech features at FFR-like rates. Using MEG, we analyzed responses in the high gamma range of 70–200 Hz to continuous speech using neural source-localized reverse correlation and the corresponding temporal response functions (TRFs). Continuous speech stimuli were presented to 40 subjects (17 younger, 23 older adults) with clinically normal hearing and their MEG responses were analyzed in the 70–200 Hz band. Consistent with the relative insensitivity of MEG to many subcortical structures, the spatiotemporal profile of these response components indicated a cortical origin with ∼40 ms peak latency and a right hemisphere bias. TRF analysis was performed using two separate aspects of the speech stimuli: a) the 70–200 Hz carrier of the speech, and b) the 70–200 Hz temporal modulations in the spectral envelope of the speech stimulus. The response was dominantly driven by the envelope modulation, with a much weaker contribution from the carrier. Age-related differences were also analyzed to investigate a reversal previously seen along the ascending auditory pathway, whereby older listeners show weaker midbrain FFR responses than younger listeners, but, paradoxically, have stronger cortical low frequency responses. In contrast to both these earlier results, this study did not find clear age-related differences in high gamma cortical responses to continuous speech. Cortical responses at FFR-like frequencies shared some properties with midbrain responses at the same frequencies and with cortical responses at much lower frequencies.HighlightsCortical MEG responses time-lock at 80–90 Hz to continuous speechResponses primarily driven by high gamma rate fluctuations of the speech envelopeResponse strength and latency are similar for younger and older adults
Tracking dynamic adjustments to decision making and performance monitoring processes in conflict tasks
Authors: Feuerriegel Daniel , Jiwa Matthew , Turner William F , Andrejević Milan , Hester Robert , Bode Stefan 
Published: December 2019

AbstractHow we exert control over our decision-making has been investigated using conflict tasks, which involve stimuli containing elements that are either congruent or incongruent. In these tasks, participants adapt their decision-making strategies following exposure to incongruent stimuli. According to conflict monitoring accounts, conflicting stimulus features are detected in medial frontal cortex, and the extent of experienced conflict scales with response time (RT) and frontal theta-band activity in the electroencephalogram (EEG). However, the consequent adjustments to decision processes following response conflict are not well-specified. To characterise these adjustments and their neural implementation we recorded EEG during a modified Flanker task. We traced the time-courses of performance monitoring processes (frontal theta) and multiple processes related to perceptual decision-making. In each trial participants judged which of two overlaid gratings forming a plaid stimulus (termed the S1 target) was of higher contrast. The stimulus was divided into two sections, which each contained higher contrast gratings in either congruent or incongruent directions. Shortly after responding to the S1 target, an additional S2 target was presented, which was always congruent. Our EEG results suggest enhanced sensory evidence representations in visual cortex and reduced evidence accumulation rates for S2 targets following incongruent S1 stimuli. Results of a follow-up behavioural experiment indicated that the accumulation of sensory evidence from the incongruent (i.e. distracting) stimulus element was adjusted following response conflict. Frontal theta amplitudes positively correlated with RT following S1 targets (in line with conflict monitoring accounts). Following S2 targets there was no such correlation, and theta amplitude profiles instead resembled decision evidence accumulation trajectories. Our findings provide novel insights into how cognitive control is implemented following exposure to conflicting information, which is critical for extending conflict monitoring accounts.
Parallel two-sided assembly line balancing with tools and tasks sharing
Authors: Yadav Ashish , Kulhary Ramawatar , Nishad Rupesh , Agrawal Sunil 
Published: December 2019

Purpose
Parallel two-sided assembly lines are usually designed to produce large-sized products such as trucks and buses. In parallel two-sided assembly lines, both left and right sides of the line are used for manufacturing one or more products on two or more assembly lines located parallel to each other. The purpose of this paper is to develop a new mathematical model for the parallel two-sided assembly line balancing problem that helps to evaluate and validate the balancing operations of the machines such as removal of tools and fixtures and reallocating the operators.

Design/methodology/approach
The proposed approach is explained with the help of an example problem. In all, 22 test problems are formed using the benchmark problems P9, P12, P16 and P24. The results obtained are compared among approaches of the task(s) shared, tool(s) shared and both tool(s) and task(s) shared for effect on efficiency as the performance measure. The solution presented here follows the exact solution procedure that is solved by Lingo 16 solver.

Findings
Based on the experiments, line efficiency decreases when only tools are shared and increases when only tasks are shared. Results indicate that by sharing tasks and tools together, better line efficiency is obtained with less cost of tools and fixtures.

Practical implications
According to the industrial aspect, the result of the study can be beneficial for assembly of the products, where tools and tasks are shared between parallel workstations of two or more parallel lines.

Originality/value
According to the author’s best knowledge, this paper is the first to address the tools and tasks sharing between any pair of parallel workstations.
The latest Millennials (1995-2000): examining within-group work ethic
Authors: Hess James P. 
Published: December 2019

Purpose
The purpose of this study is to examine the latest Millennials, born between 1995 and 2000, to determine any significant impact of gender, employment status and living arrangement on Meriac et al.’s (2013) dimensions of work ethic.

Design/methodology/approach
A factorial analysis of variance (ANOVA) was used to identify the main and interaction effects between variables. A one-way ANOVA then revealed any statistical significance between factor combinations to determine the meaningfulness of the interactions.

Findings
Morality/ethics, the centrality of work and hard work were not significantly impacted by any factors, whereas interaction effects between gender and employment status with self-reliance and wasted time were not attributed to any particular factor level. Yet, meaningful interaction resulted in gender and employment status with leisure and delay of gratification. Specifically, women who work 20 h or less per week have less regard for leisure than men, regardless of men’ employment status. Men who work 20 h or less per week have a higher acceptance of delay of gratification than women with the same employment status.

Practical implications
Understanding the youngest Millennials’ unique paradigms about work ethic will benefit managers as they blend them with those of other working cohorts to enhance job-to-employee fit by building and sustaining recruitment, motivation and retention efforts among all workforce members.

Originality/value
This study expands existing literature by focussing on the youngest Millennials so that scholar-practitioners can closely align contemporary leadership and organisation with any unique attitudes towards work ethic and, perhaps, guide leadership transition as the next cohort emerges.
Open innovation in the semiconductor industry: analysis of Brazilian design houses
Authors: Oliveira Xênia L'amour Campos , Olave Maria Elena Leon , Moreno Edward David , Silva Glessia 
Published: December 2019

Purpose
This study aims to understand how Brazilian design houses (DHs) use open innovation in joint development projects for integrated circuits.

Design/methodology/approach
As a research strategy, qualitative research using multiple case studies was made. As sources of evidence, semi-structured interviews were conducted with three DHs of Programa integrated circuit [circuito integrado(CI)]-Brasil and with four specialists in the field, as well as analysis of documents. The data were analyzed through content analysis.

Findings
The results showed the DHs use sources of external knowledge in their innovation process, to assist the development of new products, to access new knowledge and skills, to attract financial resources and to be competitive in the market of high technology.

Originality/value
The study has important implications on the semiconductor industry in Brazil, as the industry is considered strategic for the competitiveness of final goods sector. The importance of encouraging the development of partnerships in the sector, the possibility of using informal agreements to mediate the collaboration between DHs and external agents, and the improvement and long-term continuity of public policies to support the industry are among the implications. In addition to suggestions for new business approaches to assist the strengthening of this segment.
Improving employees’ intellectual capacity for cybersecurity through evidence-based malware training
Authors: He Wu , Ash Ivan , Anwar Mohd , Li Ling , Yuan Xiaohong , Xu Li , Tian Xin 
Published: December 2019

Purpose
An organization’s ability to successfully manage intellectual capital is determined by the actions of its employees to prevent or minimize information security incidents. To prevent more data breaches to intellectual capital, organizations must provide regular cybersecurity awareness training for all personnel. The purpose of this paper is to investigate the effect of different evidence-based cybersecurity training methods on employees’ cybersecurity risk perception and self-reported behavior.

Design/methodology/approach
The study participants were randomly assigned into four groups (i.e. malware report, malware videos, both malware report and malware videos and no interventions) to assess the effects of cybersecurity training on their perceptions of vulnerability, severity, self-efficacy, security intention as well as their self-reported cybersecurity behaviors.

Findings
The results show that evidence-based malware report is a relatively better training method in affecting employees’ intentions of engaging in recommended cybersecurity behaviors comparing with the other training methods used in this study. A closer analysis suggests whether the training method contains self-relevant information could make a difference to the training effects.

Originality/value
This paper reports an in-depth investigation on how different evidence-based cybersecurity training methods impact employees’ perceptions of susceptibility, severity, self-efficacy, security intention as well as on their self-reported cybersecurity behaviors.
Ethical leaders manage conflict to develop trust
Authors: Wong Alfred , Wang Xiaohui , Wang Xinyan , Tjosvold Dean 
Published: December 2019

PurposeThe purpose of this paper is to propose that effective ethical leaders develop high quality relationships with team members; in particular, they manage their conflicts with team members cooperatively.Design/methodology/approachThe authors empirically tested this hypothesis with responses from 117 managers and 302 subordinates.FindingsThrough cooperative conflict management, leaders develop trusting, mutually committed relationships. Ethical leaders and their employees avoid competitive conflict where they try to impose their ideas and resolutions on each other.Practical implicationsThe findings suggest that ethical leaders can have a significant impact by fostering cooperative conflict management and reducing competitive conflict management. Thus, organizations are encouraged to adopt training and selection procedures to develop more ethical leaders.Originality/valueThis study adds to leadership research that effective leaders develop high quality relationships that help them influence employees as well as to be open and influenced by them.