bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emotional and behavioural phenotypes in young people with neurodevelopmental CNVs
Authors: Cunningham Adam C , Hall Jeremy , Einfeld Stewart , Owen Michael J , van den Bree Marianne B M 
Published: January 2020

AbstractBackgroundA number of disorders caused by copy number variants (CNVs) are associated with a high risk of neurodevelopmental and psychiatric disorders and cognitive impairments (ND-CNVs). Few studies of ND-CNVs have investigated the emotional and behavioural problems that are important outcomes in young people with developmental and intellectual disabilities using appropriate measures.Methods322 young people with 13 ND-CNVs across eight loci (mean age:9.79 years, range:6.02-17.91, 66.5% male) took part in the study. Primary carers completed the Developmental Behaviour Checklist (DBC).ResultsSixty-seven percent of individuals with an ND-CNV screened positive for clinically significant difficulties. Young people from families with higher incomes (OR=0.71, CI=0.55 – 0.92, p=.009) were less likely to screen positive. Young people born after prolonged labour (OR=2.87, CI=1.18-8.13, p=.030) were more likely to screen positive. The rate of difficulties differed depending on ND-CNV genotype (Deviance=25.83, p=.011), with the lowest rate in 22q11.2 deletion (46%) and the highest in 1q21.1 deletion (87.5%). Individuals with inherited ND-CNVs had greater difficulties (F=6.54, df=1, p=.012, ηp2=.050), including higher self-absorbed (F=5.01, df=1, p=.027, ηp2=.039) and communication disturbance scores (F=9.13, df=1, p=.003, ηp2=.068). Specific patterns of strengths and weaknesses were found for different ND-CNV genotypes. However, ND-CNV genotype explained no more than 7-16% of variance, depending on subdomain.ConclusionsBehavioural and emotional problems are common in young people with ND-CNVs. The ND-CNV specific patterns we find can provide a basis for more tailored support. More research is needed to better understand the variation in behavioural and emotional problems not accounted for by genotype.
Multi-tissue epigenetic analysis of the osteoarthritis susceptibility locus mapping to the plectin genePLEC
Authors: Sorial A.K. , Hofer I.M.J , Tselepi M. , Cheung K. , Parker E. , Deehan D.J. , Rice S.J. , Loughlin J. 
Published: January 2020

ObjectiveOsteoarthritis (OA) associated single nucleotide polymorphism (SNP) rs11780978 correlates with differential expression ofPLEC, and methylation quantitative trait loci (mQTLs) atPLECCpGs in cartilage. This implies that methylation links chondrocyte genotype and phenotype, thus driving the functional effect.PLECencodes plectin, a cytoskeletal protein that enables tissues to respond to mechanical forces. We sought to assess whetherPLECfunctional effects were cartilage specific.MethodCartilage, fat pad, synovium and peripheral blood were collected from patients undergoing arthroplasty.PLECCpGs were analysed for mQTLs and allelic expression imbalance (AEI) was performed. We focussed on previously reported mQTL clusters neighbouring cg19405177 and cg14598846. Plectin was knocked down in a mesenchymal stem cell (MSC) line using CRISPR/Cas9 and cells phenotyped by RNA-sequencing.ResultsNovel mQTLs were discovered in fat pad, synovium and peripheral blood at both clusters. The genotype-methylation effect of rs11780978 was stronger in cg14598846 than in cg19405177 and stronger in joint tissues than in peripheral blood. We observed AEI in synovium in the same direction as for cartilage. Knocking-down plectin impacted on pathways reported to have a role in OA, including Wnt signalling, glycosaminoglycan biosynthesis and immune regulation.ConclusionsSynovium is also a target of the rs11780978 OA association functionally operating onPLEC. In fat pad, mQTLs were identified but these did not correlate withPLECexpression, suggesting the functional effect is not joint-wide. Our study highlights interplay between genetic risk, DNA methylation and gene expression in OA, and reveals clear differences between tissues from the same diseased joint.
Evaluation of M2-like macrophage enrichment after diffuse traumatic brain injury through transient interleukin-4 expression from engineered mesenchymal stromal cells
Authors: Enam S. F. , Kader S. R. , Bodkin N. , Lyon J. G. , Calhoun M. , Azrak C. , Tiwari P. M. , Vanover D. , Wang H. , Santangelo P. J. , Bellamkonda R. V. 
Published: January 2020

AbstractAppropriately modulating inflammation after traumatic brain injury (TBI) may prevent disabilities for the millions of those inflicted annually. In TBI, cellular mediators of inflammation, including macrophages and microglia, possess a range of phenotypes relevant for an immunomodulatory therapeutic approach. It is thought that early phenotypic modulation of these cells will have a cascading healing effect. In fact, an anti-inflammatory, “M2-like” macrophage phenotype after TBI has been associated with neurogenesis, axonal regeneration, and improved white matter integrity. There already exists clinical trials seeking an M2-like bias through mesenchymal stem/stromal cells (MSCs). However, MSCs do not endogenously synthesize key signals that induce robust M2-like phenotypes such as Interleukin-4 (IL-4). To enrich M2-like macrophages in a clinically relevant manner, we augmented MSCs to transiently express IL-4 via synthetic IL-4 mRNA. We observed that these IL-4 expressing MSCs indeed induce a robust M2-like macrophage phenotype and promote anti-inflammatory gene expression in a modified TBI model of closed head injury. However, here we demonstrate that acute enrichment of M2-like macrophages did not translate to improved functional or histological outcomes. This suggests that an acute enrichment of M2-like macrophages cannot solely orchestrate the neurogenesis, axonal regeneration, and improved WMI after diffuse TBI. To further understand whether dysfunctional pathways underlie the lack of therapeutic effect, we report transcriptomic analysis of injured and treated brains. Through this, we discovered that inflammation persists in spite of acute enrichment of M2-like macrophages in the brain. Last, we comment on our modified TBI model, behavioral studies, and propose that IL-4 expressing MSCs may also have relevance in other cavitary diseases or in improving biomaterial integration into tissues.
Sonogenetics for noninvasive and cellular-level neuromodulation in rodent brain
Authors: Yang Yaoheng , Pacia Christopher Pham , Ye Dezhuang , Zhu Lifei , Baek Hongchae , Yue Yimei , Yuan Jinyun , Miller Mark J. , Cui Jianmin , Culver Joseph P. , Bruchas Michael R. , Chen Hong 
Published: January 2020

AbstractSonogenetics, which uses ultrasound to noninvasively control cells genetically modified with ultrasound-sensitive ion channels, can be a powerful tool for investigating intact brain circuits. Here we show that TRPV1 is an ultrasound-sensitive ion channel that can modify the activity of TRPV1-expressing cellsin vitrowhen exposing to focused ultrasound. We also show that focused ultrasound exposure at the mouse brainin vivocan selectively activate neurons that are genetically modified to express TRPV1. We demonstrate that precise manipulation of neural activity via TRPV1-based sonogenetics can be achieved by spatiotemporal control of ultrasound-induced heating. The focused ultrasound exposure is safe based on our inspection of neuronal integrity, apoptosis, and inflammation markers. This sonogenetic tool enables noninvasive, cell-type specific, spatiotemporally controlled modulation of mammalian brain activity.
Revising CX3CR1 expression on murine classical and non-classical monocytes
Authors: Meghraoui-Kheddar A. , Barthelemy S. , Boissonnas A. , Combadière C. 
Published: January 2020

AbstractIn mice, monocytes (Mo) are conventionally described as CX3CR1lowclassical Mo (CMo) and CX3CR1highnon-classical Mo (NCMo) based on the expression level of EGFP in Cx3cr1+/EGFPmice and by analogy with human CX3CR1 expression. Although this terminology is widely used, very few works assessed the strict correlation between EGFP reporter and CX3CR1 expression. Using an unsupervised multiparametric analysis of blood Mo in steady state and after sterile peritonitis, we observed no difference in CX3CR1 expression between CMo and NCMo. Our results highlight that despite being a reliable reporter to discriminate Mo subpopulations, EGFP level in Cx3cr1+/EGFPmice does not reflect CX3CR1 expression measured by a fluorescently-labeled CX3CL1 chemokine and a CX3CR1 specific antibody. In conclusion, authors should be cautious not to identify murine classical and non-classical Mo as CX3CR1lowand CX3CR1highbut rather use alternative markers such as the combination of Ly6C and CD43.
Efficient long fragment editing technique enables large-scale and scarless bacterial genome engineering
Authors: Huang Chaoyong , Guo Liwei , Wang Jingge , Wang Ning , Huo Yi-Xin 
Published: January 2020

ABSTRACTBacteria are versatile living systems that enhance our understanding of nature and enable biosynthesis of valuable chemicals. Long fragment editing techniques are of great importance for accelerating bacterial genome engineering to obtain desirable and genetically stable strains. However, the existing genome editing methods cannot meet the needs of engineers. We herein report an efficient long fragment editing method for large-scale and scarless genome engineering inEscherichia coli. The method enabled us to insert DNA fragments up to 12 kb into the genome and to delete DNA fragments up to 186.7 kb from the genome, with positive rates over 95%. We applied this method forE. coligenome simplification, resulting in 12 individual deletion mutants and four cumulative deletion mutants. The simplest genome lost a total of 370.6 kb of DNA sequence containing 364 open reading frames. Additionally, we applied this technique to metabolic engineering and obtained a genetically stable plasmid-independent isobutanol production strain that produced 1.3 g/L isobutanol via shake-flask fermentation. These results suggest that the method is a powerful genome engineering tool, highlighting its potential to be applied in synthetic biology and metabolic engineering.
Cortical ignition dynamics is tightly linked to the core organisation of the human connectome
Authors: Castro Samy , El-Deredy Wael , Battaglia Demian , Orio Patricio 
Published: January 2020

AbstractThe capability of cortical regions to flexibly sustain an “ignited” state of activity has been discussed in relation to conscious perception or hierarchical information processing. Here, we investigate how the intrinsic propensity of different regions to get ignited is determined by the specific topological organisation of the structural connectome. More specifically, we simulated the resting-state dynamics of mean-field whole-brain models and assessed how dynamic multi-stability and ignition differ between a reference model embedding a realistic human connectome, and alternative models based on a variety of randomised connectome ensembles. We found that the strength of global excitation needed to first trigger ignition in a subset of regions is substantially smaller for the model embedding the empirical human connectome. Furthermore, when increasing the strength of excitation, the propagation of ignition outside of this initial core –which is able to self-sustain its high activity– is way more gradual than for any of the randomised connectomes, allowing for graded control of the number of ignited regions. We explain both these assets in terms of the exceptional weighed core-shell organisation of the empirical connectome, speculating that this topology of human structural connectivity may be attuned to support an enhanced ignition dynamic.Author summaryThe activity of the cortex in mammals constantly fluctuates in relation to cognitive tasks, but also during rest. The ability of brain regions to display ignition, a fast transition from low to high activity is central for the emergence of conscious perception and decision making. Here, using a biophysically inspired model of cortical activity, we show how the structural organization of human cortex supports and constrains the rise of this ignited dynamics in spontaneous cortical activity. We found that the weighted core-shell organization of the human connectome allows for a uniquely graded ignition. This graded ignition implies a smooth control of the ignition in cortical areas tuned by the global excitability. The smooth control cannot be replicated by surrogate connectomes, even though they conserve key local or global network properties. Indeed, the first trigger of ignition in the human cortex has the lowest global excitability and corresponds with the strongest interconnected areas, the ignition core. Finally, we suggest developmental and evolutionary constraints of the mesoscale organization that support this enhanced ignition dynamics in cortical activity.
Spreading predictability in complex networks
Authors: Zhao Na , Wang Jian , Yu Yong , Zhao Jun-Yan , Chen Duan-Bing 
Published: January 2020

AbstractSpreading dynamics analysis is an important and interesting topic since it has many applications such as rumor or disease controlling, viral marketing and information recommending. Many state-of-the-art researches focus on predicting infection scale or threshold. Few researchers pay attention to the predicting of infection nodes from a snapshot. With developing of precision marketing, recommending and, controlling, how to predict infection nodes precisely from snapshot becomes a key issue in spreading dynamics analysis. In this paper, a probability based prediction model is presented so as to estimate the infection nodes from a snapshot of spreading. Experimental results on synthetic and real networks demonstrate that the model proposed could predict the infection nodes precisely in the sense of probability.
Courtship behaviour reveals temporal regularity is a critical social cue in mouse communication
Authors: Perrodin Catherine , Verzat Colombine , Bendor Daniel 
Published: January 2020

SummaryWhile animals navigating the real world face a barrage of sensory input, their brains evolved to perceptually compress multidimensional information by selectively extracting the features relevant for survival. Notably, communication signals supporting social interactions in several mammalian species consist of acoustically complex sequences of vocalizations. However, little is known about what information listeners extract from such time-varying sensory streams. Here, we utilize female mice’s natural behavioural response to male courtship songs to identify the relevant acoustic dimensions used in their social decisions. We found that females were highly sensitive to disruptions of song temporal regularity, and preferentially approached playbacks of intact over rhythmically irregular versions of male songs. In contrast, female behaviour was invariant to manipulations affecting the songs’ sequential organization, or the spectro-temporal structure of individual syllables. The results reveal temporal regularity as a key acoustic cue extracted by mammalian listeners from complex vocal sequences during goal-directed social behaviour.
Energetics of stochastic BCM type synaptic plasticity and storing of accurate information
Authors: Karbowski Jan 
Published: January 2020

AbstractExcitatory synaptic signaling in cortical circuits is thought to be metabolically expensive. Two fundamental brain functions, learning and memory, are associated with long-term synaptic plasticity, but we know very little about energetics of these slow biophysical processes. This study investigates the energy requirement of information storing in plastic synapses for an extended version of BCM plasticity with a decay term, stochastic noise, and nonlinear dependence of neuron’s firing rate on synaptic current (adaptation). It is shown that synaptic weights in this model exhibit bistability. In order to analyze the system analytically, it is reduced to a simple dynamic mean-field for a population averaged plastic synaptic current. Next, using the concepts of nonequilibrium thermodynamics, we derive the energy rate (entropy production rate) for plastic synapses and a corresponding Fisher information for coding presynaptic input. That energy, which is of chemical origin, is primarily used for battling fluctuations in the synaptic weights and presynaptic firing rates, and it increases steeply with synaptic weights, and more uniformly though nonlinearly with presynaptic firing. At the onset of synaptic bistability, Fisher information and memory lifetime both increase sharply, by a few orders of magnitude, but the plasticity energy rate changes only mildly. This implies that a huge gain in the precision of stored information does not have to cost large amounts of metabolic energy, which suggests that synaptic information is not directly limited by energy consumption. Interestingly, for very weak synaptic noise, such a limit on synaptic coding accuracy is imposed instead by a derivative of the plasticity energy rate with respect to the mean presynaptic firing, and this relationship has a general character that is independent of the plasticity type. An estimate for primate neocortex reveals that a relativemetabolic cost of BCM type synaptic plasticity, as a fraction of neuronal cost related to fast synaptic transmission and spiking, can vary from negligible to substantial, depending on the synaptic noise level and presynaptic firing.
Variable environments select for short lifespan
Authors: Lind Martin I. , Ratikainen Irja I. , Andersson Johan , Carlsson Hanne , Krieg Therese , Larva Tuuli , Maklakov Alexei A. 
Published: January 2020

AbstractThe role of environmental variation in the evolution of lifespan is contested. Classic theory suggests that variable environments result in evolution of long life but novel theoretical breakthroughs show that environmental variation can instead select for short lifespan when the changes are rapid relative to generation time. Here we combined simulation modelling and experimental evolution to study the evolution of lifespan in response to temperature variation to provide the first empirical test of the new theory. Genetically diverse populations of the outcrossing nematodeCaenorhabditis remanei, were exposed to a novel, stressful temperature for 30 generations, in either stable, slowly increasing or fluctuating temperature regimes. We found evolution of shorter lifespan in populations evolving in rapidly fluctuating environments both in simulation models and in real populations supporting the new theory. While climate warming is predicted to increase environmental stochasticity, our results show that fast temperature cycles rapidly select for short lifespan.
Sleeping with your enemies – and what happens later
Authors: Barlik Jacek 
Published: January 2020

Purpose
The purpose of this paper is to find out how organizations communicate with their opponents during crises and later.

Design/methodology/approach
Qualitative research that is interviews with crisis communication professionals in Poland was conducted to explore their opinions, attitudes and practices toward opponents in crises, communication tools employed, methods of settling conflicts and ways of getting along with the former opponents later.

Findings
Communication and crisis managers provided in-depth insights on how they approach opponents during crises and later. Even though public relations professionals are aware that communicating with activist or hostile publics in times of turmoil is important, they pay more attention to internal publics and media. Senior executives often perceive media and journalists as crucial channels to reach out to different stakeholder groups during crises. Ongoing communication with opponents (or former opponents) – also after crises – mostly remains a high call for public relations professionals.

Originality/value
This paper contributes to corporate and crisis communication research by presenting how opponent publics are handled by communication professionals in crises. It shows that most organizations need to rethink their crisis strategies to include opponents in their relationship building, and to maintain these relationships with former opponents beyond the time of crisis.
Making of an entrepreneur: a journey with leather – MVR Leathers
Authors: Murthy Venkatesh , G. Jaganth 
Published: January 2020

Learning outcomes
The case discussion will help the participants figure out ways the entrepreneur could handle problems such as labour shortage, demonetisation and customer retention and find possible strategies to overcome them.

Case overview/synopsis
MVR Leathers is a small-scale leather-processing unit located in Chennai. MVR was the brainchild of Venkat Raj, who started his career in 1982 as a casual labourer in an unrelated domain. His unwavering persistence helped him to become an independent entrepreneur by 2008. In achieving his dream to become an entrepreneur, Raj encountered many challenges and an equal number of new opportunities. Each time he faced a challenge, he met a new set of people who helped him. However, at times, the same people who had helped him once might throw him out of the scene. In brief, his struggle is never-ending. He keeps fighting to come back and find new avenues to success. A different set of challenges surfaced as he took charge of his firm as a sole owner. Once again, he countered those challenges with courage and grit. In doing so, he made full use of his experience.

Complexity academic level
The case can be used for discussions at the executive, postgraduate and undergraduate levels. Academic courses that address topics such as entrepreneurship, entrepreneurs, small-firm strategies, business environments, leather industry, leadership, human resource management and entrepreneurial journeys can use the case for classroom learning.

Supplementary materials
Teaching Notes are available for educators only.

Subject code
CSS 3: Entrepreneurship.
Extra care housing: exploring motivations, expectations and perceptions
Authors: Buckland Michael James , Tinker Anthea 
Published: January 2020

Purpose
The purpose of this paper is to explore and compare the motivations and expectations that older people have when choosing to move into either a private or housing association (HA) extra care housing (ECH) scheme, and any effects this had on its residents.

Design/methodology/approach
This qualitative study is based on findings from four HA schemes in Tower Hamlets, London, and one private scheme in Warwickshire. Eight semi-structured interviews were conducted with five women and three men of varying backgrounds, from schemes managed by different associations and companies. Interview transcripts were coded and analysed thematically.

Findings
All residents moved into ECH in response to deteriorating health. However, almost all residents had felt obliged to move by others, generally their children. Few residents had any expectations of ECH on arrival, but many developed high expectations of an increased sense of independence and security and of an improved social life. ECH appeared to be beneficial for residents’ health and well-being.

Research limitations/implications
The inability to recruit an equal number of people from HA and private scheme, alongside the small sample size, may compromise the external validity of any conclusions drawn from any comparisons.

Practical implications
This research identifies a lack of knowledge about ECH among the general population and offers insight into areas of poor management within ECH schemes which could be improved.

Social implications
Inadequacies in the ECH model could be attributed to failures in the current health and social care system. Differences between expectations and perceptions of HA vs private schemes should be acknowledged and responded to.

Originality/value
This is a rare example of research exploring the relationships between ECH residents’ motivations and expectations (Hillcoat-Nallétamby and Sardani, 2019), and between those in HA vs private schemes.