bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fast event-related mapping of population fingertip tuning properties in human sensorimotor cortex at 7T
Authors: Khalife Sarah , Francis Susan T. , Schluppeck Denis , Sánchez-Panchuelo Rosa-Maria , Besle Julien 
Published: January 2022

AbstractfMRI studies that investigate somatotopic tactile representations in the human cortex typically use either block or phase-encoded stimulation designs. Event-related (ER) designs allow for more flexible and unpredictable stimulation sequences than the other methods, but they are less efficient. Here we compared an efficiency-optimized fast ER design (2.8s average intertrial interval, ITI) to a conventional slow ER design (8s average ITI) for mapping voxelwise fingertip tactile tuning properties in the sensorimotor cortex of 6 participants at 7 Tesla. The fast ER design yielded more reliable responses compared to the slow ER design, but with otherwise similar tuning properties. Concatenating the fast and slow ER data, we demonstrate in each individual brain the existence of two separate somatotopically-organized tactile representations of the fingertips, one in the primary somatosensory cortex (S1) on the post-central gyrus, and the other shared across the motor and pre-motor cortices on the pre-central gyrus. In both S1 and motor representations, fingertip selectivity decreased progressively, from narrowly-tuned Brodmann areas 3b and 4a respectively, towards associative parietal and frontal regions that responded equally to all fingertips, suggesting increasing information integration along these two pathways. In addition, fingertip selectivity in S1 decreased from the cortical representation of the thumb to that of the pinky.Significance StatementSensory and motor cortices in the human brain contain map-like representations of the body in which adjacent brain regions respond to adjacent body parts. The properties of these somatotopic maps provide important insight into how tactile and motor information is processed by the brain. Here, we describe an efficient mapping method using functional MRI to measure somatotopic maps and their tuning properties. We used a fast event-related sequence to map the five fingers of the left hand in six human participants, and show that this method is more efficient than a conventional, slower event-related design. Furthermore, we confirm previously-identified tuning properties of fingertip representations in somatosensory cortex, and reveal a hitherto unknown tactile fingertip map in the motor cortex.
Serine 1283 in extracellular matrix glycoprotein Reelin is crucial for Reelin’s function in brain development
Authors: Kleene Ralf , Loers Gabriele , Sharaf Ahmed , Wang Shaobo , Kataria Hardeep , Anstötz Max , Hermans-Borgmeyer Irm , Schachner Melitta 
Published: January 2022

AbstractDeficiency in the extracellular matrix glycoprotein Reelin severely affects migration of neurons during development. The function of serine at position 1283 in Reelin has remained uncertain. To explore its relevance we generatedrlnA/Amice that carry alanine instead of serine at position 1283, thereby disrupting the putative casein kinase 2 (CK2) phosphorylation site S1283DGD. Mutated mice displayedreeler-like locomotor behavior, abnormal brain anatomy and decrease of Reelin RNA and protein levels during development and in adulthood. Since serine 1283 was previously proposed to mediate proteolysis of adhesion molecules, we investigated proteolysis of cell adhesion molecule L1 and found it normal inrlnA/Amice. Neuronal migration in the embryonicrlnA/Acerebral cortex was impaired, but rescued byin uteroelectroporation of the Reelin fragment N-R6 containing the putative CK2 phosphorylation site. InrlnA/Amice migration of cerebellar granule cellsin vitrowas promoted by application of wild-type but not by mutated Reelin. In cerebellar neuron cultures, Reelin expression was decreased upon inhibition of ecto-phosphorylation by CK2. Biochemically purified wild-type, but not mutated Reelin was found phosphorylated. Altogether, the results indicate that ecto-phosphorylation at serine 1283 rather than proteolytic processing of adhesion molecules by Reelin plays an important role in Reelin functions.
Liver-derived cell lines from cavefish Astyanax mexicanus as an in vitro model for studying metabolic adaptation
Authors: Krishnan Jaya , Wang Yan , Kenzior Olga , Huzaifa Hassan , Olsen Luke , Tsuchiya Dai , Wang Yongfu , Zhao Chongbei , Rohner Nicolas 
Published: January 2022

AbstractCell lines have become an integral resource and tool for conducting biological experiments ever since the Hela cell line was first developed (1). They not only allow detailed investigation of molecular pathways but are faster and more cost-effective than most in vivo approaches. The last decade saw many emerging model systems strengthening basic science research. However, lack of genetic and molecular tools in these newer systems pose many obstacles. Astyanax mexicanus is proving to be an interesting new model system for understanding metabolic adaptation. To further enhance the utility of this system, we developed liver-derived cell lines from both surface-dwelling and cave-dwelling morphotypes. In this study, we provide detailed methodology of the derivation process along with a comprehensive biochemical and molecular characterization of the cell lines, which reflects key metabolic traits of cavefish adaptation. We anticipate these cell lines to become a useful resource for the Astyanax community as well as researchers investigating fish biology, comparative physiology, and metabolism.
scRNA-sequencing reveals subtype-specific transcriptomic perturbations in DRG neurons ofPirt-EGFPfmice in neuropathic pain condition
Authors: Zhang Chi , Hu Ming-Wen , He Shao-Qiu , Wang Xue-Wei , Cao Xu , Zhou Feng-Quan , Qian Jiang , Guan Yun 
Published: January 2022

AbstractFunctionally distinct subtypes/clusters of dorsal root ganglion (DRG) neurons, which differ in soma size and neurochemical properties, may play different roles in nerve regeneration and pain. However, details about transcriptomic changes in different neuronal subtypes under maladaptive neuropathic pain conditions remain unclear. Chronic constriction injury (CCI) of the sciatic nerve represents a well-established model of neuropathic pain that mimics the etiology of clinical conditions. Therefore, we conducted single-cell RNA-sequencing (scRNA-seq) to characterize subtype-specific perturbations of transcriptomes in lumbar DRG neurons 7 days after sciatic CCI. By usingPirt-EGFPfmice that selectively express enhanced green fluorescent protein in DRG neurons, we established a highly efficient purification process to enrich neurons for scRNA-seq. We observed a loss of marker genes in injured neurons of 12 standard neuronal clusters, and the emergence of four prominent CCI-induced clusters at this peak-maintenance phase of neuropathic pain. Importantly, a portion of injured neurons from a subset of the 12 standard clusters (NP1, PEP5, NF1, and NF2) were spared from injury-induced identity loss, suggesting subtype-specific transcriptomic changes in injured neurons. Moreover, uninjured neurons, which are necessary for mediating the evoked pain, also demonstrated subtype-specific transcriptomic perturbations in these clusters, but not others. Notably, male and female mice showed differential transcriptomic changes in multiple neuronal clusters after CCI, suggesting transcriptomic sexual dimorphism in primary sensory neurons after nerve injury. Collectively, these findings may contribute to the identification of new target genes and development of DRG neuron subtype-specific therapies for optimizing neuropathic pain treatment and nerve regeneration.
Metastable Oscillatory Modes emerge from synchronization in the Brain Spacetime Connectome
Authors: Cabral Joana , Castaldo Francesca , Vohryzek Jakub , Litvak Vladimir , Bick Christian , Lambiotte Renaud , Friston Karl , Kringelbach Morten L. , Deco Gustavo 
Published: January 2022

AbstractA rich repertoire of oscillatory signals is detected from human brains with electro- and magnetoencephalography (EEG/MEG). However, the principles underwriting coherent oscillations and their link with neural activity remain under debate. Here, we revisit the mechanistic hypothesis that transient brain rhythms are a signature of metastable synchronization, occurring at reduced collective frequencies due to delays between brain areas. We consider a system of damped oscillators in the presence of background noise – approximating the short-lived gamma-frequency oscillations generated within neuronal circuits – coupled according to the diffusion weighted tractography between brain areas. Varying the global coupling strength and conduction speed, we identify a critical regime where spatially and spectrally resolved metastable oscillatory modes (MOMs) emerge at sub-gamma frequencies, approximating the MEG power spectra from 89 healthy individuals at rest. Further, we demonstrate that the frequency, duration, and scale of MOMs – as well as the frequency-specific envelope functional connectivity – can be controlled by global parameters, while the connectome structure remains unchanged. Grounded in the physics of delay-coupled oscillators, these numerical analyses demonstrate how interactions between locally generated fast oscillations in the connectome spacetime structure can lead to the emergence of collective brain rhythms organized in space and time.
Malformations of the sacculus and the semicircular canals in spider morph pythons
Authors: Starck J. Matthias , Schrenk Fabian , Schröder Sofia , Pees Michael 
Published: January 2022

AbstractSpider morph ball pythons are a frequently bred design morph with striking alterations of the skin color pattern. We created high resolution µCT-image series through the otical region of the skulls, used 3D-reconstruction software for rendering anatomical models, and compare the anatomy of the semicircular ducts, sacculus and ampullae of wildtypePython regius(ball python) with spider morph snakes. All spider morph snakes showed the wobble condition. We describe the inner ear structures in wild-type and spider-morph snakes and report a deviant morphology of semicircular canals, ampullae and sacculus in spider morph snakes. We also report about associated differences in the desmal skull bones of spider morph snakes. The spider morph snakes were characterized by wider semicircular canals, anatomically poorly defined ampulla, a deformed crus communis and a small sacculus, with a highly deviant x-ray morphology as compared to wildtype individuals. We observed considerable intra- and interindividual variability of these features. This deviant morphology of spider morph snakes can easily be associated with an impairment of sense of equilibrium and the observed neurological wobble condition. Limitations in sample size prevent statistical analyses, but the anatomical evidence is strong enough to support an association between the wobble condition in design bread spider morph snakes and a malformation of the inner ear structures. A link between artificially selected alterations in pattern and specific color design with neural-crest associated developmental malformations of the statoacoustic organ as known from other vertebrates is discussed.
A unified view of low complexity regions (LCRs) across species
Authors: Lee Byron , Jaberi-Lashkari Nima , Calo Eliezer 
Published: January 2022

ABSTRACTLow complexity regions (LCRs) play a role in a variety of important biological processes, yet we lack a unified view of their sequences, features, relationships, and functions. Here, we use dotplots and dimensionality reduction to systematically define LCR type/copy relationships and create a map of LCR sequence space capable of integrating LCR features and functions. By defining LCR relationships across the proteome, we provide insight into how LCR type and copy number contribute to higher order assemblies, such as the importance of K-rich LCR copy number for assembly of the nucleolar protein RPA43 in vivo and in vitro. With LCR maps, we reveal the underlying structure of LCR sequence space, and relate differential occupancy in this space to the conservation and emergence of higher order assemblies, including the metazoan extracellular matrix and plant cell wall. Together, LCR relationships and maps uncover and identify scaffold-client relationships among E-rich LCR-containing proteins in the nucleolus, and revealed previously undescribed regions of LCR sequence space with signatures of higher order assemblies, including a teleost-specific T/H-rich sequence space. Thus, this unified view of LCRs enables discovery of how LCRs encode higher order assemblies of organisms.
Determinants of trafficking, conduction, and disease within a K+ channel revealed through multiparametric deep mutational scanning
Authors: Coyote-Maestas Willow , Nedrud David , He Yungui , Schmidt Daniel 
Published: January 2022

AbstractA longstanding goal in protein science and clinical genetics is to develop quantitative models of sequence, structure, and function relationships and delineate the mechanisms by which mutations cause disease. Deep Mutational Scanning (DMS) is a promising strategy to map how amino acids contribute to protein structure and function and to advance clinical variant interpretation. Here, we introduce 7,429 single residue missense mutation into the Inward Rectifier K+ channel Kir2.1 and determine how this affects folding, assembly, and trafficking, as well as regulation by allosteric ligands and ion conduction. Our data provides high-resolution information on a cotranslationally­folded biogenic unit, trafficking and quality control signals, and segregated roles of different structural elements in fold-stability and function. We show that Kir2.1 trafficking mutants are underrepresented in variant effect databases, which has implications for clinical practice. By comparing fitness scores with expert-reviewed variant effects, we can predict the pathogenicity of ‘variants of unknown significance’ and disease mechanisms of know pathogenic mutations. Our study in Kir2.1 provides a blueprint for how multiparametric DMS can help us understand the mechanistic basis of genetic disorders and the structure-function relationships of proteins.
Proteomic Dissection of a Giant Cell
Authors: Lin Athena , Piehowski Paul D. , Tsai Chia-Feng , Makushok Tatyana , Yi Lian , Diaz Ulises , Yan Connie , Summers Diana , Sood Pranidhi , Smith Richard D. , Liu Tao , Marshall Wallace F. 
Published: January 2022

SummaryMany individual proteins have been identified as having defined positions relative to cell polarity axes, raising the question of what fraction of all proteins may have polarized localizations. We took advantage of the giant ciliate Stentor coeruleus to quantify the extent of polarized localization proteome-wide. This trumpet-shaped unicellular organism shows a clear morphological anterior-posterior axis defined by a circular array of cilia known as a membranellar band at one end, and a holdfast at the other end. Because individual Stentor cells are over a millimeter in length, we were able to cut the cells into three pieces along the anterior-posterior axis, followed by proteomic analysis of proteins enriched in each piece. We find that approximately 30% of all detected proteins show a polarized location relative to the anterior-posterior cell axis. Proteins with polarized enrichment include centrin-like proteins, calcium-regulated kinases, orthologs of SFI1 and GAS2, and proteases. At the organelle level, nuclear and mitochondrial proteins are enriched in the anterior half of the cell body, but not in the membranellar band itself, while ribosome related proteins are apparently uniformly distributed. RNAi of signaling proteins enriched in the membranellar band, which is the anterior-most structure in the cell, revealed a protein phosphatase 2 subunit b ortholog required for closure of the membranellar band into the ring shape characteristic of Stentor. These results suggest that a large fraction of the Stentor proteome has a polarized localization, and provide a protein-level framework for future analysis of pattern formation and regeneration in Stentor as well as defining a general strategy for subcellular spatial proteomics based on physical dissection of cells.
Multiomic characterisation of high grade serous ovarian carcinoma enables high resolution patient stratification
Authors: Hollis Robert L , Meynert Alison M , Michie Caroline O , Rye Tzyvia , Churchman Michael , Hallas-Potts Amelia , Croy Ian , McCluggage W. Glenn , Williams Alistair R W , Bartos Clare , Iida Yasushi , Okamoto Aikou , Dougherty Brian , Barrett J. Carl , March Ruth , Matakidou Athena , Roxburgh Patricia , Semple Colin A , Harkin D Paul , Kennedy Richard , Herrington C Simon , Gourley Charlie 
Published: January 2022

ABSTRACTBackgroundHigh grade serous ovarian carcinoma (HGSOC) is the most common type of ovarian cancer; most patients experience disease recurrence which accumulates chemoresistance, leading to treatment failure. Previous investigations have characterised HGSOC at the genomic and transcriptomic level, identifying subtypes of patients with differential outcome and treatment response. However, the relationship between molecular events identified at the gene sequence, gene copy number and gene expression levels remains poorly defined.MethodsWe perform multi-layer molecular characterisation of a large retrospective HGSOC cohort (n=362) with detailed clinical annotation to interrogate the relationship between patient groups defined by gene mutation, copy number events, gene expression patterns and infiltrating immune cell burden. We construct a high resolution picture of the molecular landscape in HGSOC and identify features of tumours associated with distinct clinical behaviour in patients.ResultsBRCA2-mutant (BRCA2m) andEMSY-overexpressing cases demonstrated prolonged survival (multivariable hazard ratio 0.40 and 0.53) and higher chemotherapy response rates at first- and second-line treatment.CCNE1-gained (CCNE1g) cases demonstrated shorter survival (multivariable hazard ratio 1.52, 95% CI 1.10-2.10), under-representation of FIGO stage IV cases (P=0.017) and no significant difference in treatment response. We demonstrate marked overlap between the TCGA- and derived subtypes: the TCGA DIF, IMR, PRO and MES subtypes correlated with the Tothill C4, C2, C5 and C1 subtypes (P<0.001). IMR/C2 cases displayed higherBRCA1/2m frequency (25.5% and 32.5%) and significantly greater infiltration of immune cells (P<0.001), while PRO/C5 cases had the highestCCNE1g rate (23.9% and 22.2%) and were uniformly low in immune cell infiltration. The survival benefit for cases with aberrations in homologous recombination repair (HRR) genes was apparent across all transcriptomic subtypes (hazard ratio range 0.48-0.68). There was significant co-occurrence of RB loss and HRR gene aberrations (P=0.005); RB loss was further associated with favourable survival within cases harbouring HRR aberrations (multivariable hazard ratio 0.50, 95% CI 0.30-0.84).ConclusionsThese data paint a high resolution picture of the molecular landscape in HGSOC, better defining patients who may benefit most from specific molecular therapeutics and highlighting those for whom novel treatment strategies are needed to improve outcomes.
Using bibliometric analysis to map innovative business models for vertical farm entrepreneurs
Authors: Biancone Paolo Pietro , Brescia Valerio , Lanzalonga Federico , Alam Gazi Mahabubul 
Published: January 2022

PurposeThis paper aims to explore the literature on vertical farming to define key elements to outline a business model for entrepreneurs. The research aims to stimulate entrepreneurship for vertical farming in a smart cities' context, recognising urban agriculture as technology to satisfy increasing food needs.Design/methodology/approachThe research conducts a structured literature review on 186 articles on vertical farming extracted from the Scopus. Moreover, the bibliometric analysis revealed the descriptive statistics on this field and the main themes through the authors' keywords.FindingsDifferent perspectives showed the multidisciplinary nature of the topic and how the intersection of different skills is necessary to understand the subject entirely. The keywords analysis allowed for identifying the topics covered by the authors and the business model's elements.Research limitations/implicationsThe research explores a topic in the embryonic stage to define key strands of literature. It provides business model insights extending George and Bock's (2011) research to stimulate entrepreneurship in vertical farming. Limitations arise from the sources used to develop our analysis and how the topic appears as a frontier innovation.Originality/valueOriginality is the integration of literature strands related to vertical farming, highlighting its multidisciplinary nature to provide a holistic understanding of the themes. In smart cities' context, innovations allow traditional business models to be interpreted in a novel perspective and revealed the elements for transforming vertical farming from innovative technology to an effective source of food sustenance. Finally, the paper suggests a new methodology application for the analysis of word clusters by integrating correspondence analysis and multidimensional scaling analysis.
Gender, talent management and firm performance: MNCs' female-focused talent management practices in Russia
Authors: Latukha Marina , Michailova Snejina , Ott Dana L. , Khasieva Daria , Kostyuk Darya 
Published: January 2022

PurposeThere is a substantial void in the understanding of the effect of talent management (TM) practices specifically targeted at females on firm performance. This paper investigates the relationship between female-focused TM and firm performance with the aim of demonstrating the importance of gender diversity in firms.Design/methodology/approachThe authors developed and empirically tested a contextually embedded model using data from 103 multinational corporations in Russia to examine the effect of female-focused TM on firm performance.FindingsThe authors found an overall positive relationship between female-focused TM and firm performance. The authors’ analysis also revealed significant positive effects of female-focused talent development and talent retention, but not talent attraction, on firm performance.Originality/valueThis paper contributes to the vibrant TM scholarship by focusing on female-focused talent attraction, development and retention practices.