bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning-based clustering of nanosized fluorescent extracellular vesicles
Authors: Kuypers Sören , Smisdom Nick , Pintelon Isabel , Timmermans Jean-Pierre , Ameloot Marcel , Michiels Luc , Hendrix Jelle , Hosseinkhani Baharak
Published: November 2020

Extracellular vesicles (EV) are biological nanoparticles that play an important role in cell-to-cell communication. The phenotypic profile of EV populations is a promising reporter of disease, with direct clinical diagnostic relevance. Yet, robust methods for quantifying the biomarker content of EV have been critically lacking, and require a single-particle approach due to their inherent heterogeneous nature. Here, we used multicolor single-molecule burst analysis microscopy to detect multiple biomarkers present on single EV. We classified the recorded signals and applied the machine learning-based t-distributed stochastic neighbor embedding algorithm to cluster the resulting multidimensional data. As a proof of principle, we applied the method to assess both the purity and the inflammatory status of EV, and compared cell culture and plasma-derived EV isolated via different purification methods. We then applied this methodology to identify intercellular adhesion molecule-1 (ICAM-1) specific EV subgroups released by inflamed endothelial cells, and to prove that apolipoprotein-a1 is an excellent marker to identify the typical lipoprotein contamination in plasma. Our methodology can be widely applied on standard confocal microscopes, thereby allowing both standardized quality assessment of patient plasma EV preparations, and diagnostic profiling of multiple EV biomarkers in health and disease.
Precise spatial representations in the hippocampus of a food‑caching bird
Authors: Payne Hannah L. , Lynch Galen F. , Aronov Dmitriy
Published: November 2020

The hippocampus is an ancient neural circuit required for the formation of episodic memories. In mammals, this ability is thought to depend on well-documented patterns of neural activity, including place cells and sharp wave ripples. Notably, neither pattern has been found in non-mammals, despite compelling examples of episodic-like memory across a wide range of vertebrates. Does episodic memory nonetheless have a universal implementation across distant neural systems? We addressed this question by recording neural activity in the hippocampus of the tufted titmouse – an intense memory specialist from a food-caching family of birds. These birds cache large numbers of food items at scattered, concealed locations and use hippocampus-dependent memory to retrieve their caches. We found remarkably precise spatial representations akin to classic place cells, as well as sharp wave ripples, in the titmouse hippocampus. These patterns were organized along similar anatomical axes to those found in mammals. In contrast, spatial coding was weaker in a different, non-food-caching bird species. Our findings suggest a striking conservation of hippocampal mechanisms across distant vertebrates, in spite of vastly divergent anatomy and cytoarchitecture. At the same time, these results demonstrate that the exact implementation of such common mechanisms may conform to the unique ethological needs of different species.
Measuring stimulus-evoked neurophysiological differentiation in distinct populations of neurons in mouse visual cortex
Authors: Mayner William G. P. , Marshall William , Billeh Yazan N. , Gandhi Saurabh R. , Caldejon Shiella , Cho Andrew , Griffin Fiona , Hancock Nicole , Lambert Sophie , Lee Eric , Luviano Jennifer , Mace Kyla , Nayan Chelsea , Nguyan Thuyanh , North Kat , Seid Sam , Williford Ali , Cirelli Chiara , Groblewski Peter , Lecoq Jerome , Tononi Giulio , Koch Christof , Arkhipov Anton
Published: November 2020

Despite significant progress in understanding neural coding, it remains unclear how the coordinated activity of large populations of neurons relates to what an observer actually perceives. Since neurophysiological differences must underlie differences among percepts, differentiation analysis—quantifying distinct patterns of neurophysiological activity—is an “inside out” approach that addresses this question. We used two-photon calcium imaging in mice to systematically survey stimulus-evoked neurophysiological differentiation in excitatory populations across 3 cortical layers (L2/3, L4, and L5) in each of 5 visual cortical areas (primary, lateral, anterolateral, posteromedial, and anteromedial) in response to naturalistic and phase-scrambled movie stimuli. We find that unscrambled stimuli evoke greater neurophysiological differentiation than scrambled stimuli specifically in L2/3 of the anterolateral and anteromedial areas, and that this effect is modulated by arousal state and locomotion. Contrariwise, decoding performance was far above chance and did not vary substantially across areas and layers. Differentiation also differed within the unscrambled stimulus set, suggesting that differentiation analysis may be used to probe the ethological relevance of individual stimuli.
Bi-directional control of a prelimbic somatostatin microcircuit decreases binge alcohol consumption
Authors: Dao Nigel C. , Brockway Dakota F. , Nair Malini Suresh , Crowley Nicole A.
Published: November 2020

Somatostatin neurons have been implicated in a variety of neuropsychiatric disorders such as depression and anxiety, but their role in substance abuse disorders, including alcohol use disorder (AUD), is not fully characterized. Here we found that repeat cycles of alcohol binge drinking in the Drinking-in-the-Dark (DID) model led to hypoactivity of somatostatin (SST) neuronal in the prelimbic (PL) cortex by diminishing their action potential firing capacity and excitatory/inhibitory transmission dynamic. We examined their role in regulating alcohol consumption via bidirectional chemogenetic manipulation. Both hM3Dq-induced excitation and KORD-induced silencing of PL SST neurons paradoxically reduced alcohol binge drinking in males and females, with no effect on sucrose consumption. This effect is mediated directly via monosynaptic connection from SST neurons onto pyramidal neurons and indirectly via an intermediate GABAergic source. Optogenetic-assisted circuit mapping revealed that PL SST neurons preferentially synapse onto pyramidal neurons over other GABAergic populations in males, whereas SST neuron-mediated inhibition is balanced across cell types in females. Alcohol binge drinking disinhibits pyramidal neurons by augmenting SST neurons-mediated GABA release and synaptic strength onto other GABAergic populations. Together these data suggest substantial interaction between alcohol binge drinking and SST neurons inhibitory circuit in the PL, as well as provide evidence for these neurons as a potential therapeutic candidate for the treatment of alcohol use disorders, including binge drinking.
Meiotic drive is associated with sexual incompatibility inNeurospora
Authors: Vogan Aaron , Svedberg Jesper , Grudzinska-Sterno Magdalena , Johannesson Hanna
Published: November 2020

Meiotic drive is the phenomenon whereby selfish elements bias their transmission to progeny at ratios above 50:50, violating Mendel’s law of equal segregation. The model fungusNeurosporacarries three different meiotic drivers, called Spore killers. Two of these,Sk-2andSk-3, are multilocus spore killers that constitute large haplotypes and are found in the speciesN. intermedia. Here we used molecular markers to determine that allN. intermediaisolates from New Zealand in fact belong to the sister speciesN. metzenbergii. Additionally, we use laboratory crosses to demonstrate thatSk-2andSk-3are involved in sexual incompatibility betweenN. intermediaandN. metzenbergii.. Our experiments revealed that while crosses between these two species normally produced viable progeny at appreciable rates, when strains ofN. intermediacarriedSk-2orSk-3the proportion of viable progeny dropped substantially and in some crosses, no viable progeny were observed. Backcrossings supported that the incompatibility is tightly linked to theSkhaplotype. Finally, it appears thatSk-2andSk-3have accumulated different incompatibility phenotypes when crossed withN. metzenbergiistrains, consistent with their independent evolutionary history. This research illustrates how meiotic drive can contribute to reproductive isolation between populations, and thereby speciation.
Genetically diverse populations spread faster in benign but not in challenging environments
Authors: Frederik Mortier , Stefano Masier , Dries Bonte
Published: November 2020

Population spread from a limited pool of founding propagules is at the basis of biological invasions. The size and genetic variation of these propagules eventually affect whether the invasion is successful or not. The inevitable bottleneck at introduction decreases genetic diversity, and therefore should affect population growth and spread. However, many heavily bottlenecked invasive populations have been successful in nature. These negative effects of a genetic bottleneck are typically considered to be relaxed in benign environments because of a release from stress. Despite its relevance to understand and predict invasions, empirical evidence on the role of genetic diversity in relation to habitat quality is largely lacking. We use the mite Tetranychus urticae Koch as a model to experimentally assess spread rate and the size of genetically depleted inbred populations and enriched mixed populations. This was assessed in replicated linear patch systems consisting of benign (bean), challenging (tomato) or a gradient (bean to tomato) habitat. We find that genetic diversity increased population spread rates in the benign but not in the challenging habitat. Additionally, variance in spread was consistently higher in genetically poor populations and highest in the challenging habitat. Our experiment challenges the general view that a bottleneck in genetic variation decreases invasion success in challenging, but not in benign environments.
A Large-Scale Structural and Functional Connectome of Social Mentalizing
Authors: Wang Yin , Metoki Athanasia , Xia Yunman , Zang Yinyin , He Yong , Olson Ingrid R
Published: November 2020

Humans have a remarkable ability to infer the mind of others. This mentalizing skill relies on a distributed network of brain regions but how these regions connect and interact is not well understood. Here we leveraged large-scale multimodal neuroimaging data to elucidate the connectome-level organization and brain-wide mechanisms of mentalizing processing. Key features of the mentalizing connectome have been delineated in exquisite detail and its relationship with the default mode network has been extensively scrutinized. Our study demonstrates that mentalizing processing unfolds across functionally heterogeneous regions with highly structured fiber tracts and unique hierarchical functional architecture, which make it distinguishable from the default mode network and other social brain networks.
Structural basis for variable IgE reactivities of Cor a 1 hazelnut allergens
Authors: Führer Sebastian , Kamenik Anna S. , Zeindl Ricarda , Nothegger Bettina , Hofer Florian , Reider Norbert , Liedl Klaus R. , Tollinger Martin
Published: November 2020

A major proportion of allergic reactions to hazelnuts (Corylus avellana) are caused by immunologic cross-reactivity of IgE antibodies to pathogenesis-related class 10 (PR-10) proteins. Intriguingly, the four known isoforms of the hazelnut PR-10 allergen Cor a 1, denoted as Cor a 1.0401-Cor a 1.0404, share sequence identities exceeding 97 % but possess different immunologic properties. In this work we describe the NMR solution structures of these proteins and provide an in-depth study of their biophysical properties. Despite sharing highly similar three-dimensional structures, the four isoforms exhibit remarkable differences regarding structural flexibility, hydrogen bonding and thermal stability. Our experimental data reveal an inverse correlation between structural flexibility and IgE-binding, with the most flexible isoform having the lowest IgE-binding potential, while the isoform with the most rigid backbone scaffold displays the highest immunologic reactivity. These results point towards a significant entropic contribution to the process of antibody binding.
Validation of a novel associative transcriptomics pipeline in Brassica oleracea: Identifying candidates for vernalisation response
Authors: Woodhouse Shannon , He Zhesi , Woolfenden Hugh , Steuernagel Burkhard , Haerty Wilfried , Bancroft Ian , Irwin Judith A. , Morris Richard J. , Wells Rachel
Published: November 2020

Associative transcriptomics has been used extensively in Brassica napus to enable the rapid identification of markers correlated with traits of interest. However, within the important vegetable crop species, Brassica oleracea, the use of associative transcriptomics has been limited due to a lack of fixed genetic resources and the difficulties in generating material due to self-incompatibility. Within Brassica vegetables, the harvestable product can be vegetative or floral tissues and therefore synchronisation of the floral transition is an important goal for growers and breeders. Vernalisation is known to be a key determinant of the floral transition, yet how different vernalisation treatments influence flowering in B. oleracea is not well understood.

Here, we present results from phenotyping a diverse set of 69 B. oleracea accessions for heading and flowering traits under different environmental conditions. We developed a new associative transcriptomics pipeline, and inferred and validated a population structure, for the phenotyped accessions. A genome-wide association study identified miR172D as a candidate for the vernalisation response. Gene expression marker association identified variation in expression of BoFLC.C2 as a further candidate for vernalisation response.

This study provides insights into the genetic basis of vernalisation response in B. oleracea through associative transcriptomics and confirms its characterisation as a complex G x E trait. Candidate leads were identified in miR172D and BoFLC.C2. These results could facilitate marker-based breeding efforts to produce B. oleracea lines with more synchronous heading dates, potentially leading to improved yields.
CRISPR/Cas9 targeting Ttc30a mimics ciliary chondrodysplasia with polycystic kidney disease
Authors: Getwan Maike , Hoppmann Anselm , Schlosser Pascal , Grand Kelli , Song Weiting , Diehl Rebecca , Schroda Sophie , Heeg Florian , Deutsch Konstantin , Hildebrandt Friedhelm , Lausch Ekkehart , Köttgen Anna , Lienkamp Soeren S.
Published: November 2020

Skeletal ciliopathies (e.g. Jeune syndrome, short rib polydactyly syndrome, Sensenbrenner syndrome) are frequently associated with cystic kidney disease and other organ manifestations, but a common molecular mechanism has remained elusive.

We established two models for skeletal ciliopathies (ift80andift172) inXenopus tropicalis, which exhibited severe limb deformities, polydactyly, cystic kidneys, and ciliogenesis defects, closely matching the phenotype of affected patients.

Employing data-mining and anin silicoscreen we identified candidate genes with similar molecular properties to genetically validated skeletal ciliopathy genes. Among four genes experimentally validated, CRISPR/Cas9 targeting ofttc30areplicated all aspects of the phenotypes observed in the models of genetically confirmed disease genes, including ciliary defects, limb deformations and cystic kidney disease.

Our findings establish three new models for skeletal ciliopathies (ift80,ift172,ttc30a) and identify TTC30A/B as an essential node in the network of ciliary chondrodysplasia and nephronophthisis-like disease proteins implicating post-translational tubulin modifications in its pathogenesis.
Rate of immune complex cycling in follicular dendritic cell determines the extent of protecting antigen integrity and availability to germinal center B cells1
Authors: Arulraj Theinmozhi , Binder Sebastian C. , Meyer-Hermann Michael
Published: November 2020

Follicular Dendritic Cells (FDCs) retain immune complexes (ICs) for prolonged time periods and are important for germinal center (GC) reactions. ICs undergo periodic cycling in FDCs, a mechanism supporting an extended half-life of antigen. Based on experimental data we estimated that the average residence time of Phycoerythrin-ICs (PE-ICs) on FDC surface and interior were 21 and 36 minutes, respectively. GC simulations show that antigen cycling might impact GC dynamics due to redistribution of antigen on the FDC surface and by protecting antigen from degradation. Antigen protection and influence on GC dynamics varied with antigen cycling time and total antigen concentration. Simulations predict that blocking antigen cycling terminates the GC reaction and decreases plasma cell production. Considering that cycling of antigen could be a target for the modulation of GC reactions, our findings highlight the importance of understanding the mechanism and regulation of IC cycling in FDCs.
Neural excitability and sensory input determine intensity perception with opposing directions in initial cortical responses
Authors: Stephani T. , Hodapp A. , Idaji M. Jamshidi , Villringer A. , Nikulin V. V.
Published: November 2020

Perception of sensory information is determined by stimulus features (e.g., intensity) and instantaneous neural states (e.g., excitability). Commonly, it is assumed that both are reflected similarly in evoked brain potentials, that is, higher evoked activity leads to a stronger percept of a stimulus. We tested this assumption in a somatosensory discrimination task in humans, simultaneously assessing (i) single-trial excitatory post-synaptic currents inferred from short-latency somatosensory evoked potentials (SEP), (ii) pre-stimulus alpha oscillations (8-13 Hz), and (iii) peripheral nerve measures. Fluctuations of neural excitability shaped the perceived stimulus intensity already during the very first cortical response (at ∼20 ms) yet demonstrating opposite neural signatures as compared to the effect of presented stimulus intensity. We reconcile this discrepancy via a common framework based on modulations of electro-chemical membrane gradients linking neural states and responses, which calls for reconsidering conventional interpretations of brain potential magnitudes in stimulus intensity encoding.
Recurrent dynamics of prefrontal cortex during context-dependent decision-making
Authors: Cohen Zach , DePasquale Brian , Aoi Mikio C. , Pillow Jonathan W.
Published: November 2020

A key problem in systems neuroscience is to understand how neural populations integrate relevant sensory inputs during decision-making. Here, we address this problem by training a structured recurrent neural network to reproduce both psychophysical behavior and neural responses recorded from monkey prefrontal cortex during a context-dependent per-ceptual decision-making task. Our approach yields a one-to-one mapping of model neurons to recorded neurons, and explicitly incorporates sensory noise governing the animal’s performance as a function of stimulus strength. We then analyze the dynamics of the resulting model in order to understand how the network computes context-dependent decisions. We find that network dynamics preserve both relevant and irrelevant stimulus information, and exhibit a grid of fixed points for different stimulus conditions as opposed to a one-dimensional line attractor. Our work provides new insights into context-dependent decision-making and offers a powerful framework for linking cognitive function with neural activity within an artificial model.
Dichotic listening deficits in amblyaudia are characterized by aberrant neural oscillations in auditory cortex
Authors: Momtaz Sara , Moncrieff Deborah W. , Bidelman Gavin M.
Published: November 2020

Children diagnosed with auditory processing disorder (APD) show deficits in processing complex sounds that are associated with difficulties in higher-order language, learning, cognitive, and communicative functions. Amblyaudia (AMB) is a subcategory of APD characterized by abnormally large ear asymmetries in dichotic listening tasks. Here, we examined frequency-specific neural oscillations and functional connectivity via high-density EEG in children with and without AMB during passive listening of nonspeech stimuli. Time-frequency maps of these “brain rhythms” revealed stronger phase-locked beta-gamma (∼35 Hz) oscillations in AMB participants within bilateral auditory cortex for sounds presented to the right ear, suggesting a hypersynchronization and imbalance of auditory neural activity. Brain-behavior correlations revealed neural asymmetries in cortical responses predicted the larger than normal right-ear advantage seen in participants with AMB. Additionally, we found weaker functional connectivity in the AMB group from right to left auditory cortex, despite their stronger neural responses overall. Our results reveal abnormally large auditory sensory encoding and an imbalance in communication between cerebral hemispheres (ipsi-to -contralateral signaling) in AMB. These neurophysiological changes might lead to the functionally poorer behavioral capacity to integrate information between the two ears in children with AMB.
Jack-of-all-trades paradigm meets long-term data: generalist herbivores are more widespread and locally less abundant
Authors: Sudta Chanchanok , Salcido Danielle M. , Forister Matthew L. , Walla Thomas R. , Villamarín-Cortez Santiago , Dyer Lee A.
Published: November 2020

Ecological specialization is one of the most interesting and perplexing attributes of biological systems. While certain macroecological patterns, such as an increase in specialization at lower latitudes, have long been subjects of investigation, there is much yet to be learned about inter-specific variation in specialization within diverse communities. High levels of specialization have been documented for some dominant ecological interactions, such as parasitism and herbivory, but much less is known about the relative abundance of specialists and generalists within those broad functional groups. We examine untested assumptions about the positive association between local abundance and dietary specialization using a 17-year dataset of caterpillar-plant interactions in Ecuador. Our long-term data consist of experimental verification of caterpillar-plant associations and include standardized plot-based samples as well as general, regional collections of caterpillars, allowing for investigations across spatial scales and using different indices of abundance for 1,917 morphospecies of Lepidoptera (“caterpillars”) from 33 families. We find that more specialized caterpillars are locally more abundant than generalists, consistent with a key component of the “jack of all trades, master of none” hypothesis, which has otherwise received poor to mixed support from previous studies that have mostly involved fewer species and shorter time series. At larger scales, generalists achieve greater prevalence across the landscape, and we find some evidence for geographic variation in the abundance-diet breadth relationship, in particular among elevational bands. Interspecific variation in abundance had a negative relationship with diet breadth, with specialists having more variable abundances across species. The interesting result that more specialized species can be both rare and common highlights the ecological complexity of specialization.

Statement of authorship

CS wrote the first draft of the manuscript. DMS, MLF and LAD contributed substantially to consequent drafts and revisions. LAD, TRW, SV and DMS collected field data. CS, MLF and LAD generated research questions and designed statistical analyses. CS, DMS, LAD and MLF conducted statistical analyses.

Data statement

Data supporting the results and conclusions can be found on a website caterpillars.org. Statistical analyses supporting the results are available upon request.
Continuouscis-regulatory changes in an advantageous gene are linked with adaptive radiation in cichlid fishes
Authors: Gu Langyu , Li Chenzheng , Mao Xiaobing , Wei Zongfang , Huang Youkui , He Ximin , Zhou Wenjun , Li Li , Wang Deshou
Published: November 2020

Deciphering why some lineages produce spectacular radiations while others do not provides important insights into biodiversity, but the molecular basis underlying this process remains largely unknown. Here, we identified a lineage-restricted gene, which we namedlg. Combined omics analyses showed thatlgis under positive selection in the most species-rich lineage of cichlid fishes, the modern haplochromine (MH) lineage, indicating its evolutionary advantage. Using transgenic zebrafish, we functionally showed that a cichlid fish-specific upstream insertion oflgcan drive new and strong eGFP expression in tissues noted for adaptation in the MH lineage, but not in other lineages. Furthermore, the deletion of three MH-specific SNPs within this region can reconstitute weak and limited expression patterns similar to those in non-MH lineages. We thus demonstrated that a series ofcis-regulatory changes in an advantageous gene are linked with a gain of expression that is related to an astonishingly adaptive radiative lineage.
Detection the Prevalence of Hepatitis C Virus among Iraqi People
Authors: Khudhair Hasan Abd Ali , Albakaa Ali A. H. , Hussein Khwam R.
Published: November 2020

Hepatitis C virus (HCV) infection is a major public health problem worldwide and remains a vital cause of chronic hepatitis. This study was aimed to detect the prevalence of HCV infection among Iraqi people. Four subjects of hemodialysis (HD) patients, thalassemia patients, blood donors and medical staff were enrolled in this study and evaluated for their serum anti-HCV-immunoglobulin G (IgG)-antibodies (Abs). The total frequency % of IgG anti-HCV Abs positivity was 3.2%, in which the highest frequency % was recorded among thalassemia patients followed by HD patients and then medical staff subjects, whereas the lowest frequency rate was reported within blood donors group. The frequencies of IgG anti-HCV Abs positivity were significantly elevated in males compared to females. For age groups, the results revealed higher infection rate of HCV among age group of 1-20 year followed by the age group of 21-40 year and then age group of 41-60 year, whereas the lowest rate of infection was recorded in age group >60 year. In conclusions, the prevalence rate of HCV infection among Iraqi people is similar to those in most of Asian and non-Asian studied populations and the infection rate was higher in males and inversely correlated with age of the patients. Blood transfusion, renal dialysis and health care workers (HCWs) were major sources of HCV infection. Thus, we recommend continuing surveillance of blood donors, HCWs and patients, in addition to HCV markers screening by molecular technique for the diagnosis of HCV during the window period in order to decrease the prevalence of HCV infection.
A highly contiguous genome assembly of a major forest pest, the Eurasian spruce bark beetleIps typographus
Authors: Powell Daniel , Groβe-Wilde Ewald , Krokene Paal , Roy Amit , Chakraborty Amrita , Löfstedt Christer , Vogel Heiko , Andersson Martin N , Schlyter Fredrik
Published: November 2020

The Eurasian spruce bark beetle (Ips typographus[L.]), is a major killer of spruce forests across the Palearctic. During epidemics, it can destroy over 100 million cubic meters of spruce trees in a single year. Here we report a 236 Mb, highly contiguousI. typographusgenome assembly using PacBio long-read sequencing. The final phased assembly had a contig N50of 6.65 Mb in 272 contigs and was predicted to contain 23,923 protein-coding genes. Comparative genomic analysis revealed expanded gene families associated with plant cell wall degradation, including pectinases, aspartyl proteases, and glycosyl hydrolases. In today’s forests, increasingly stressed by global warming, this resource can assist in mitigating bark beetle outbreaks by developing novel pest control strategies. Further, this first whole-genome sequence from the genusIpsprovides timely resources to address important questions about the evolutionary biology and ecology of Curculionidae, the true weevils, one of the largest animal families.
Correcting MEG artifacts caused by overt speech
Authors: Abbasi Omid , Steingräber Nadine , Gross Joachim
Published: November 2020

Recording brain activity during speech production using magnetoencephalography (MEG) can help us to understand the dynamics of speech production. However, these measurements are challenging due to the induced artifacts coming from several sources such as facial muscle activity, lower jaw and head movements. Here, we aimed to characterise speech-related artifacts and subsequently present an approach to remove these artifacts from MEG data. We recorded MEG from 11 healthy participants while they pronounced various syllables in different loudness. Head positions/orientations were extracted during speech production to investigate its role in MEG distortions. Finally, we present an artifact rejection approach using the combination of regression analysis and signal space projection (SSP) in order to correct the induced artifact from MEG data. Our results show that louder speech leads to stronger head movements and stronger MEG distortions. Our proposed artifact rejection approach could successfully remove the speech-related artifact and retrieve the underlying neurophysiological signals. As the presented artifact rejection approach was shown to remove artifacts induced by overt speech in the MEG, it will facilitate research addressing the neural basis of speech production with MEG.
De novoactivated transcription of inserted foreign coding sequences is inheritable in the plant genome
Authors: Hata Takayuki , Takada Naoto , Hayakawa Chihiro , Kazama Mei , Uchikoba Tomohiro , Tachikawa Makoto , Matsuo Mitsuhiro , Satoh Soichirou , Obokata Junichi
Published: November 2020

The manner in which inserted foreign coding sequences become transcriptionally activated and fixed in the plant genome is poorly understood. To examine such processes of gene evolution, we performed an artificial evolutionary experiment inArabidopsis thaliana. As a model of gene-birth events, we introduced a promoterless coding sequence of the firefly luciferase (LUC) gene and established 386 T2-generation transgenic lines. Among them, we determined the individualLUCinsertion loci in 76 lines and found that one-third of them were transcribedde novoeven in the intergenic or inherently unexpressed regions. In the transcribed lines, transcription-related chromatin marks were detected across the newly activated transcribed regions. These results agreed with our previous findings inA. thalianacultured cells under a similar experimental scheme. A comparison of the results of the T2-plant and cultured cell experiments revealed that thede novo-activated transcription concomitant with local chromatin remodelling was inheritable. During one-generation inheritance, it seems likely that the transcription activities of theLUCinserts trapped by the endogenous genes/transcripts became stronger, while those ofde novotranscription in the intergenic/untranscribed regions became weaker. These findings may offer a clue for the elucidation of the mechanism by which inserted foreign coding sequences become transcriptionally activated and fixed in the plant genome.
β-catenin signaling via astrocyte-encoded TCF7L2 regulates neuronal excitability and social behavior
Authors: Mateusz Szewczyk Lukasz , Andrzej Lipiec Marcin , Ewa Liszewska , Joanna Urban-Ciecko , Ludwika Kondrakiewicz , Puscian Alicja , Ewelina Knapska , Hiromi Inoue , Jan Nowakowski Tomasz , Victoria Molofsky Anna , Marta Barbara Wiśniewska
Published: November 2020

Astrocytes play essential roles in supporting neuronal activity and synapse formation; however, mechanisms by which these functions are regulated are unclear. The Wnt/β-catenin signaling pathway plays a crucial role in brain development and is implicated in neurodevelopmental disorders including autism spectrum disorder (ASD). We sought to investigate if some impacts of Wnt signaling are mediated via astrocytes. Here we show that the canonical Wnt/β-catenin pathway is active in postnatal cortical astrocytes and that its effector, the transcription factor TCF7L2 –is expressed in astrocyte lineage cells during embryonic and postnatal development in both mouse and human. Astrocyte-specific deletion ofTcf7l2in the early postnatal period led to alterations in astrocyte morphology, membrane depolarization and decreased cortical neuron excitability. Mice with the conditional knockout exhibited increased sociability and social preference in a naturalistic setting. Taken together, these data reveal a key role of astrocytic Wnt signaling in shaping postnatal neuronal development and adult social behavior.
Histone H1 protects telomeric repeats from H3K27me3 invasion inArabidopsis
Authors: Teano Gianluca , Concia Lorenzo , Wolff Léa , Carron Léopold , Biocanin Ivona , Adamusová Kateřina , Fojtová Miloslava , Bourge Michael , Kramdi Amira , Colot Vincent , Grossniklaus Ueli , Bowler Chris , Baroux Célia , Carbone Alessandra , Probst Aline V. , Procházková Schrumpfová Petra , Fajkus Jiří , Amiard Simon , Grob Stefan , Bourbousse Clara , Barneche Fredy
Published: November 2020

While the pivotal role of linker histone H1 in shaping nucleosome organization is well established, its functional interplays with chromatin factors along the epigenome are just starting to emerge. Here we first report that inArabidopsis, as in mammals, H1 occupies Polycomb Repressive Complex 2 (PRC2) target genes where it favors chromatin condensation and H3K27me3 deposition. We further show that, contrasting with its conserved function in PRC2 activation at genes, H1 selectively prevents H3K27me3 accumulation at telomeres and large pericentromeric interstitial telomeric repeat (ITR) domains by restricting DNA accessibility to Telomere Repeat Binding (TRB) proteins, a group of H1-related Myb factors mediating PRC2cisrecruitment. This study unveils a mechanistic framework by which H1 avoids the formation of gigantic H3K27me3-rich domains at telomeric sequences and contributes to safeguard nucleus architecture.

Abstract Figure

Teano et al. report that that linker histone H1 and a group of H1-related telomeric proteins interplay to selectively influence thePolycombrepressive landscape at genes and telomeric repeats inArabidopsis. These findings provide a mechanistic framework by which H1 influences the epigenome and nuclear organization in a sequence-specific manner.

Highlights

H1 promotes PRC2 activity and limits accessibility at a majority of genes

H1 prevents PRC2 activity at telomeric DNA sequences

PRC2 repression is achieved by restricting accessibility to TRB proteins

H1 orchestrates the spatial organization of telomeres and interstitial telomeres (ITRs)
A novel direct resolution method for coupled systems in finite element analysis
Authors: Boutora Youcef , Takorabet Noureddine
Published: November 2020

Purpose

This paper aims to propose a novel direct method for indefinite algebraic linear systems. It is well adapted for sparse linear systems, such as those of two-dimensional (2-D) finite elements problems, especially for coupled systems.

Design/methodology/approach

The proposed method is developed on an example of an indefinite symmetric matrix. The algorithm of the method is given next, and a comparison between the numbers of operations required by the method and the Cholesky method is also given. Finally, an application on a magnetostatic problem for classical methods (Gauss and Cholesky) shows the relative efficiency of the proposed method.

Findings

The proposed method can be used advantageously for 2-D finite elements in stepping methods without using a block decomposition of matrices.

Research limitations/implications

This method is advantageous for direct linear solving for 2-D problems, but it is not recommended at this time for three-dimensional problems.

Originality/value

The proposed method is the first direct solver for algebraic linear systems proposed since more than a half century. It is not limited for symmetric positive systems such as many of direct and iterative methods.
Use of current sheet coupled to an analytical tool to analyze by FEM the harmonic content of armature winding ditribution
Authors: Marault Jérôme , Tounzi Abdelmounaïm , Gillon Frédéric , Hecquet Michel
Published: November 2020

Purpose

For a given rotor, the study of the impact of stator MMF from different winding distributions is usually carried out using analytical model under some simplifying hypotheses to limit time computation. To get more accurate results, finite element model is thus more suitable. However, testing different combinations of stator windings with the same rotor can be tedious when considering the stator slots. Indeed, this introduces mesh constraint, reluctance variation of the air gap and possibly taking into account of the connection between stator coils. To avoid this, a current sheet supplied such to represent the stator MMF and spread all around the inner slotless stator surface can be used. In addition, such an approach can be very useful to didactically assess the effect of each winding space harmonic on machine performance separately. The purpose of this paper is to use a current sheet coupled to an external analytical tool in order to easily test different windings or to quantify the effect of a given spatial harmonic of the winding.

Design/methodology/approach

In the proposed approach, the current sheet supply is obtained from an analytical tool that allows determining the spatiotemporal stator MMF of any winding considered. Moreover, stator teeth height is not modelled, and only the thickness of the stator yoke is considered along with the same air gap thickness. Results with the proposed approach are compared to the real stator modelling for two different winding configurations. Last, linear and non-linear magnetic material behaviours are investigated to validate the proposed approach in term of magnetic distribution.

Findings

For both studied cases, results in term of local and global physical quantities show good agreement between the real stator modelling and the proposed approach.

Originality/value

Current sheet is used with finite element model to study the inherent effect of different winding configurations on local and global physical quantities of an AC electrical machine. The proposed approach avoids the constraints in terms of stator slot geometry and electrical circuit definition. This is very useful to quickly test different winding configurations or to isolate a specific winding space harmonic to quantify its effect on the electrical performances. This cannot be performed using classical modelling as all space harmonics are taken into account.
Pitfalls of a fledgling venture, Fetakart: in search of a viable business model
Authors: Singh Abhinava S. , Shah Mayur , Pathak Priyanka
Published: November 2020

Learning outcomes

The learning outcomes include to identify and discuss important personality characteristics of an entrepreneur, to explore the business planning pitfalls that torment many new ventures and to understand key concepts of business model thinking.

Case overview/synopsis

The case is about Fetakart, a one-year old venture, which offered custom designed and printed t-shirts in Gujarat, India. The venture was launched by Himanshu Dhadnekar in 2018. Himanshu was a young first-generation entrepreneur who displayed entrepreneurial characteristics since his school days. Later, he was involved with a few failed startups, worked as an employee in different companies and curated new ventures. Fetakart was born out of another venture, MotivPrints, which sold a large variety of custom designed and high-quality printed products such as visiting cards, office essentials, apparels, packaging and marketing material. At MotivPrints, Himanshu discovered the market for customized t-shirts in India but with very little knowledge of the business model or capabilities of leading players such as Bewakoof.com. The venture started struggling and faced several problems including high cost demands by manufacturers and lack of funding. Where did Fetakart go wrong? Was Fetakart born out of impulse? Did Himanshu have a viable business model for Fetakart?

Complexity academic level

The case can be discussed in the class of entrepreneurship at master’s level. It can also be used in entrepreneurship specialization course and strategic management elective(s) in the second year of post-graduation. The case can be particularly useful for young entrepreneurs associated as incubatees with a business incubator and for an executive development program related to new ventures.

Supplementary materials

Teaching Notes are available for educators only.

Subject code

CSS 3: Entrepreneurship.
Safeguarding children under Covid-19: What are we learning?
Authors: Pearce Jenny , Miller Chris
Published: November 2020

Purpose

The purpose of this paper is to identify and share learning about safeguarding children under Covid-19 drawn from a series of webinars held by the Association of Safeguarding Partners (www.theASP.org.uk). The learning is relevant for health, police, local authority and other relevant safeguarding agencies and includes sharing information about both the challenges and opportunities presented during the Covid-19 pandemic. By creating a webinar lead community of learning, lessons can be drawn that will help safeguard children during the remaining of the pandemic and during the release of lockdown as it emerges.

Design/methodology/approach

This paper summarises themes from discussions within three webinars run by The Association of Safeguarding Partners (TASP) (www.theASP.org.uk). Each webinar was attended by between 60 and 80 participants, sessions involving presentations and discussions on topics such as “managing safeguarding reviews at a distance”, “the impact on early years’ provision” and “how work with families and children has changed with remote working methods”. With the participants’ consent, webinars were recorded, and these can be viewed on www.theasp.co.uk. Webinars were supported by an on-line programme: “meeting sphere” capturing comments in a “chat” facility and providing capacity for participants to collectively code comments into themes.

Findings

Findings from the webinars note concerns about continuing and undetected abuse of children within and outside of the home; about the changing nature of criminal exploitation; and about the strains created by social distancing on children in families experiencing problems with poor mental health, drug and alcohol misuse and domestic abuse. Findings include some important lessons, including the discovery of innovative ways of working, the rapid collation of data across partnerships and about different methods of engaging with children, young people and families. Findings include suggestions about the impact of changes on the future safeguarding of children.

Originality/value

There is little published discussion of the implications of Covid-19 on practitioners working on safeguarding children. While some research is emerging, there have been few opportunities for practitioners to listen to emerging practice ideas under Covid-19 or to discuss in an informal context how to address the new and emerging problems in safeguarding children. This think piece contains original material from webinars held with safeguarding children practitioners and is valuable for those working to safeguard children during and post Covid-19.
Revival of the traditional handicraft enterprising community in Pakistan
Authors: Shafi Mohsin , Yin Lixi , Yuan Yue , Zoya
Published: November 2020

Purpose

This study aims to examine issues affecting the growth and survival of traditional handicraft enterprising community in Pakistan, and analyzes their strengths, weaknesses, opportunities and threats, as well as develops strategic solutions to overcome the problems identified for their revival.

Design/methodology/approach

This exploratory study is based on a descriptive approach because it attempts to investigate the critical issues faced by traditional handicraft enterprising community. To operationalize the theoretical approach, this paper used a SWOT analysis of craft enterprising community. After thoroughly reviewing relevant literature, this study put forward strategic solutions for the revival of the traditional enterprising community. Moreover, secondary data on employment and gender wage gap were used to provide empirical evidence of the issues identified and emphasize the importance of strategic solutions.

Findings

This study found that traditional handicraft producers are facing many problems that hinder their survival and growth. This paper, therefore, makes some essential strategic recommendations on how to overcome these issues. The current research argues that Pakistan’s handicraft industry must be revived; else, centuries-old traditional culture and patrimonial knowledge will vanish. Moreover, there is a need to attract foreign investment to overcome resource limitations and improve the competitive capability of the enterprising community. Notably, government intervention is necessary for the revival of the traditional handicraft industry.

Originality/value

This study provides in-depth knowledge of issues faced by the Pakistani traditional handicraft enterprising community and suggests possible strategic solutions for the problems identified. Unlike previous studies, this research also discusses the essential characteristics of traditional handicrafts that differentiate them from identical mechanized products.
From development to exploitation of digital health solutions: lessons learnt through multidisciplinary research and consultancy
Authors: Bul Kim , Holliday Nikki , Magee Paul , Wark Petra
Published: November 2020

Purpose

This viewpoint paper provides an overview of lessons learnt throughout the whole cycle of development to exploitation of digital solutions in health and wellbeing settings. This paper aims to address learnings that can be applied to all digital health technologies, including assistive technologies, apps, wearables, medical devices and serious games.

Design/methodology/approach

Based on the knowledge and experiences of working within a multidisciplinary team, the authors discuss lessons learnt through research and consultancy projects in digital health and translate these into pragmatic suggestions and recommendations.

Findings

Firstly, the importance of collaborating and co-creating with multidisciplinary stakeholders and end users throughout the whole project lifecycle is emphasised. Secondly, digital health solutions are not a means to an end, nor a panacea; decisions should be evidence-based and needs-driven. Thirdly, whenever possible, research designs and tools need to be more adaptive and personalised. Fourthly, the use of a mixed-method system approach and continuous evaluation throughout the project’s lifecycle is recommended to build up the evidence base. Fifthly, to ensure successful exploitation and implementation, a business case and timely bottom-up approach is recommended. Finally, to prevent research waste, it is our shared responsibility to collaborate with existing consortia and create an awareness of existing solutions and approaches.

Originality/value

In conclusion, collaborating in the field of digital health offered insights into how to be more purposeful and effective in development, evaluation and exploitation of digital health solutions. Moving this diverse and dynamic field forward is challenging but will contribute to greater long-term impact on society.