bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lymphatics constitute a novel component of the intestinal stem cell niche
Authors: Goto Norihiro , Imada Shinya , Deshpande Vikram , Yilmaz Ömer H. 
Published: January 2022

SUMMARYIntestinal stem cells (ISCs) depend on niche factors for their proper function. However, the source of these ISC niche factors and how they support ISCs remain controversial due to their redundant expression patterns. Here, we report that the maintenance of ISCs depends on both lymphatic endothelial cells (LECs) and Rspo3+Grem1+ fibroblasts (RGFs). We found that LECs are surrounded by RGFs and located in close proximity to Lgr5+ ISCs. RSPO3 production is restricted to LECs and RGFs and they can partially compensate for each other; however, RSPO3 loss in both of LECs and RGFs drastically compromises ISC numbers, villi length, and repair after irradiation-induced injury. Mechanistically, irradiation-induced damage expands LEC and RGF numbers and enhances the latter’s generation of RSPO3 through IL-1 receptor activation. We propose that LECs represent a novel component of the ISC niche, which together with RGFs, provide essential RSPO3 to sustain ISCs in homeostasis and regeneration.
A role for heritable transcriptomic variation in maize adaptation to temperate environments
Authors: Sun Guangchao , Yu Huihui , Wang Peng , Guerrero Martha Lopez , Mural Ravi V. , Mizero Olivier N. , Grzybowski Marcin , Song Baoxing , van Dijk Karin , Schachtman Daniel P. , Zhang Chi , Schnable James C. 
Published: January 2022

ABSTRACTTranscription bridges genetic information and phenotypes. Here, we evaluated how changes in transcriptional regulation enable maize (Zea mays), a crop originally domesticated in the tropics, to adapt to temperate environments. We generated 572 unique RNA-seq datasets from the roots of 340 maize genotypes. Genes involved in core processes such as cell division, chromosome organization and cytoskeleton organization showed lower heritability of gene expression. While genes involved in anti-oxidation activity exhibited higher expression heritability. An expression genome-wide association study (eGWAS) identified 19,602 expression quantitative trait loci (eQTLs) associated with the expression of 11,444 genes. A GWAS for alternative splicing identified 49,897 splicing QTLs (sQTLs) for 7,614 genes. Rare allele burden within genomic intervals withtrans-eQTLs correlated with extremes of expression in target genes as previously reported forcis-eQTLs. Genes harboring bothcis-eQTLs andcis-sQTLs in linkage disequilibrium were disproportionately likely to encode transcription factors or were annotated as responding to one or more stresses. Independent component analysis of gene expression data identified loci regulating co-expression modules involved in phytohormone pathways, cell wall biosynthesis, lipid metabolism and stress response. Several genes involved in cell proliferation, flower development, DNA replication and gene silencing showed lower gene expression variation explained by genetic factors between temperate and tropical maize lines. A GWAS of 27 previously published phenotypes identified several candidate genes overlapping with genomic intervals showing signatures of selection during adaptation to temperate environments. Our results illustrate how maize transcriptional regulatory networks enable changes in transcriptional regulation to adapt to temperate regions.
Single-cell Transcriptome and Accessible Chromatin Dynamics During Endocrine Pancreas Development
Authors: Duvall Eliza , Benitez Cecil M. , Tellez Krissie , Enge Martin , Pauerstein Philip T. , Li Lingyu , Baek Songjoon , Quake Stephen R. , Smith Jason P. , Sheffield Nathan C. , Kim Seung K. , Arda H. Efsun 
Published: January 2022

ABSTRACTDelineating gene regulatory networks that orchestrate cell-type specification is an ongoing challenge for developmental biology studies. Single-cell analyses offer opportunities to address these challenges and accelerate discovery of rare cell lineage relationships and mechanisms underlying hierarchical lineage decisions. Here, we describe the molecular analysis of pancreatic endocrine cell differentiation using single-cell gene expression, chromatin accessibility assays coupled to genetic labeling and cell sorting. We uncover transcription factor networks that delineate β-, α- and δ-cell lineages. Through genomic footprint analysis we identify transcription factor-regulatory DNA interactions governing pancreatic cell development at unprecedented resolution. Our analysis suggests that the transcription factor Neurog3 may act as a pioneer transcription factor to specify the pancreatic endocrine lineage. These findings could improve protocols to generate replacement endocrine cells from renewable sources, like stem cells, for diabetes therapy.
On the clinical benefit of on-scalp MEG: A modeling study of on-scalp MEG epileptic activity source estimation ability
Authors: Westin Karin , Beniczky Sándor , Hämäläinen Matti , Lundqvist Daniel 
Published: January 2022

AbstractObjectiveWhole-head on scalp magnetoencephalography (osMEG) is a novel, cutting-edge functional neuroimaging technique that positions MEG sensors closer to the cortical sources. OsMEG allows both for free head movements and improved spatial resolution compared to conventional MEG. OsMEG thus might improve clinical epilepsy evaluations. However, it remains largely unknown how osMEG characterizes epileptic activity. Here, we aimed to compare epileptic activity source estimation accuracy of osMEG, high-density EEG (hd-EEG), conventional MEG (convMEG) and subdural EEG (sbdEEG).MethodIED and seizure onset zone source estimations of osMEG, hdEEG, convMEG and sbdEEG were evaluated using equivalent current dipoles. Cancellation index of all non-invasive modalities were calculated and compared statistically. To further investigate any similarity between osMEG and sbdEEG, representational similarity analysis was used to compare IED source estimations of these two modalities.ResultsWe found that osMEG IED source estimations were significantly (p<0.05) better than both convMEG and hdEEG. Furthermore, osMEG mesial temporal lobe SOZ source estimations were superior to those of convMEG and hdEEG. OsMEG cancellation index did not differ significantly from convMEG. Interestingly, comparing osMEG and sbdEEG IED source estimation demonstrated that osMEG might be less sensitive to source directions than convMEG.ConclusionWe demonstrated that whole-head osMEG exhibited very accurate non-invasive IED and SOZ source estimations, better than both hd-EEG and convMEG.SignificanceOsMEG has a promising potential to become a safe, highly sensitive neuroimaging modality for whole head epilepsy evaluations.HighlightsAnalysis of novel on-scalp MEG (osMEG) sensors in epilepsy evaluationsCompares osMEG, EEG, conventional MEG & intracranial EEG epilepsy source estimationsOur study demonstrates potential great clinical value of osMEG whole-head sensors
Inserting Cre Recombinase into the Prolactin 8a2 gene for Decidua-Specific recombination in Mice
Authors: Dickson Mackenzie J. , Oh Yeong Seok , Gruzdev Artiom , Li Rong , Balaguer Nuria , Kelleher Andrew M. , Spencer Thomas E. , Wu San-Pin , DeMayo Francesco J. 
Published: January 2022

AbstractAn estimated 75% of unsuccessful pregnancies are due to implantation failure. Investigating the causes of implantation failure is difficult as decidualization and embryo implantation is a dynamic process. Here we describe a new decidua specific iCre recombinase mouse strain. Utilizing CRISPR/Cas9-based genome editing, a mouse strain was developed that expresses iCre recombinase under the control of the endogenous prolactin family 8, subfamily a, member 2 (Prl8a2) promoter. iCre recombinase activity was examined by crossing with mTmG or Sun1-GFP reporter alleles. iCre activity initiated reporter expression at gestational day 5.5 in the primary decidual zone and continued into mid-gestation (gestational day 9.5), with expression highly concentrated in the anti-mesometrial region. No reporter expression was observed in the ovary, oviduct, pituitary, or skeletal muscle, supporting the tissue specificity of the Prl8a2iCre in the primary decidual zone. This novel iCre line will be a valuable tool for in vivo genetic manipulation and lineage tracing to investigate functions of genetic networks and cellular dynamics associated with decidualization and infertility.
CRY-BARs: Versatile light-gated molecular tools for the remodeling of membrane architectures
Authors: Wurz Anna I. , Bunner Wyatt Paul , Szatmari Erzsebet M. , Hughes Robert M. 
Published: January 2022

AbstractBAR (Bin, Amphiphysin and Rvs) protein domains are responsible for the generation of membrane curvature and represent a critical mechanical component of cellular functions. Thus, BAR domains have great potential as components of membrane-remodeling tools for cell biologists. In this work, we describe the design and implementation of a family of versatile light-gated I-BAR domain containing tools (‘CRY-BARs’) with applications in the remodeling of membrane architectures and the control of cellular dynamics. By taking advantage of the intrinsic membrane binding propensity of the I-BAR domain, CRY-BARs can be used for spatial and temporal control of cellular processes that require induction of membrane protrusions. Using cell lines and primary neuron cultures, we demonstrate that the CRY-BAR optogenetic tool reports membrane dynamic changes associated with cellular activity. Moreover, we provide evidence that Ezrin acts as a relay between the plasma membrane and the actin cytoskeleton and therefore is an important mediator of switch function. Overall, CRY-BARs hold promise as a useful addition to the optogenetic toolkit to study membrane remodeling in live cells.
Evaluation of P. aeruginosa attachment on mineralized collagen scaffolds and addition of manuka honey to increase mesenchymal stem cell osteogenesis
Authors: Dewey Marley J. , Collins Alan J. , Tiffany Aleczandria , Barnhouse Victoria R. , Lu Crislyn , Kolliopoulos Vasiliki , Hickok Noreen J. , Harley Brendan A.C. 
Published: January 2022

ABSTRACTThe design of biomaterials to regenerate bone is likely to increasingly require modifications that reduce bacterial attachment and biofilm formation as infection during wound regeneration can significantly impede tissue repair and typically requires surgical intervention to restart the healing process. Here, we investigate the ability of a mineralized collagen biomaterial to natively resist infection as well as how the addition of manuka honey affects bacterial colonization and mesenchymal stem cell osteogenesis. We incorporate manuka honey into these scaffolds via either direct fabrication into the scaffold microarchitecture or via soaking the scaffold in a solution of Manuka honey after fabrication. Direct incorporation results in a change in the surface characteristics and porosity of mineralized collagen scaffolds. Soaking scaffolds in honey concentrations greater than 10% had significant negative effects on mesenchymal stem cell metabolic activity but soaking or incorporating 5% honey had no impact on endothelial cell tube formation. Soaking and incorporating 5% honey into scaffolds reduced metabolic activity of mesenchymal stem cells, however, soaking 5% honey into scaffolds increased calcium and phosphorous mineral formation, osteoprotegerin release, and alkaline phosphatase activity. The addition of manuka honey did not prevent P. aeruginosa attachment but may be able to limit attachment of other common wound-colonizing bacteria. Overall, our results demonstrate the potential for soaking mineralized collagen scaffolds in 5% manuka honey to increase osteogenesis of mesenchymal stem cells.
Molecular markers of mechanosensation in glycinergic neurons in the avian lumbosacral spinal cord
Authors: Stanchak Kathryn E. , Miller Kimberly E. , Lumsden Eric W. , Shikiar Devany , Davis Calvin , Brunton Bingni W. , Perkel David J. 
Published: January 2022

AbstractBirds are exceptionally adept at controlling their body position. For example, they can coordinate rapid movements of their body while stabilizing their head. Intriguingly, this ability may rely in part on a mechanosensory organ in the avian lower spinal cord called the lumbosacral organ (LSO). However, molecular mechanotransduction mechanisms have not been identified in the avian spinal cord. Here, we report the presence of glycinergic neurons in the LSO that exhibit immunoreactivity for myosin7a and epsin, molecules essential for function and maintenance of hair cells in the inner ear. Specifically, we find glycinergic cell bodies near the central canal and processes that extend laterally to the accessory lobes and spinal ligaments. These LSO neurons are reminiscent of glycinergic neurons in a recently-described lateral spinal proprioceptive organ in zebrafish that detects spinal bending. The avian LSO, however, is located inside a series of fused vertebrae called the synsacrum, which constrains spinal bending. We suggest the LSO may be a modification and elaboration of a pre-existing mechanosensory spinal network in vertebrates. A mechanistic understanding of its function may be an important clue to understanding the evolution and development of avian locomotion.
Cryo-EM structure of RNA-induced tau fibrils reveals a small C-terminal core that may nucleate fibril formation
Authors: Abskharon Romany , Sawaya Michael R. , Boyer David R. , Cao Qin , Nguyen Binh A. , Cascio Duilio , Eisenberg David S. 
Published: January 2022

AbstractIn neurodegenerative diseases including Alzheimer’s and ALS, proteins that bind RNA are found in aggregated forms in autopsied brains. Evidence suggests that RNA aids nucleation of these pathological aggregates; however, the mechanism has not been investigated at the level of atomic structure. Here we present the 3.4 Å resolution structure of fibrils of full-length recombinant tau protein in the presence of RNA, determined by electron cryo-microscopy (cryoEM). The structure reveals the familiar in-register cross-β amyloid scaffold, but with a small fibril core spanning residues Glu391 to Ala426, a region disordered in the fuzzy coat in all previously studied tau polymorphs. RNA is bound on the fibril surface to the positively charged residues Arg406 and His407 and runs parallel to the fibril axis. The fibrils dissolve when RNAse is added, showing that RNA is necessary for fibril integrity. While this structure cannot exist simultaneously with the tau fibril structures extracted from patients’ brains, it could conceivably account for the nucleating effects of RNA cofactors followed by remodeling as fibrils mature.Significance statementApplication of cryoEM has greatly expanded our understanding of atomic structures of mature pathological amyloid fibrils, but little is known at the molecular level of the initiation of fibril formation. RNA has been shown to be one cofactor for formation of fibrils of tau protein, and is known also to bind to other proteins, including TDP-43, FUS, and HNRNPA2, which form pathological inclusions. Our cryoEM structure of recombinant tau protein with RNA reveals a 36 residue, C-terminal fibril core bound to RNA which runs parallel to the fibril axis. We speculate that this structure could represent an early step in the formation of tau fibrils.
The genome sequence ofHirschfeldia incana, a species with high photosynthetic light-use efficiency
Authors: Garassino Francesco , Wijfjes Raúl Y. , Boesten René , Becker Frank F. M. , Clapero Vittoria , van den Hatert Iris , Holmer Rens , Schranz M. Eric , Harbinson Jeremy , de Ridder Dick , Smit Sandra , Aarts Mark G. M. 
Published: January 2022

AbstractPhotosynthesis is a biophysical and biochemical process that plays a key role in sustaining plant and human life, being the first step in the production of energy-rich molecules and oxygen in the biosphere. Improving the photosynthetic capacity of agricultural crops is highly desirable to increase their yields. While the core mechanisms of photosynthesis are highly conserved, certainly in higher plants, plants that can maintain a high photosynthetic light-use efficiency at high irradiance are exceptional and may be useful to understand and improve high irradiance photosynthesis of crops. One such exceptional species isHirschfeldia incana, a member of the well-studied Brassicaceae family that is easy to grow under standard laboratory conditions, providing an excellent resource for studying the genetic and physiological basis of this trait. Here, we present a reference assembly ofH. incanaand affirm its high photosynthetic efficiency relative to the Brassicaceae speciesBrassica rapa, Brassica nigra, andArabidopsis thaliana. We estimate that it diverged fromB. rapaandB. nigra10-11 million years ago and that its genome has diversified from that of the latter two species through large chromosomal rearrangements, species-specific transposon activity, and differential retention of duplicated genes. Genes present at copy numbers different fromB. rapaandB. nigrainclude those involved in photosynthesis and/or abiotic stress, which may mediate the high photosynthetic efficiency ofH. incana. We expect the reference assembly ofH. incanato be a valuable genomic resource for identifying ways to enhance photosynthetic rates in crop species.
Antibodies to native gluten arise from cross-reactive B cells with implications for epitope spreading in celiac disease
Authors: Zhou Chunyan , Østerbye Thomas , Dahal-Koirala Shiva , Steinsbø Øyvind , Jahnsen Jørgen , Lundin Knut E. A. , Buus Søren , Sollid Ludvig M. , Iversen Rasmus 
Published: January 2022

ABSTRACTAntibodies to deamidated gluten peptides are accurate diagnostic markers of celiac disease (CeD). However, antibody binding to all possible gluten epitopes has not previously been investigated. To map antibody reactivity in detail and to understand the connection between disease-relevant B-cell and T-cell epitopes, we took advantage of a high-density peptide array for assessment of serum antibody specificity in CeD across the wheat gluten proteome. We confirm the importance of peptide deamidation for antibody binding, and we show that the response is remarkably focused on the known epitope QPEQPFP (where E results from deamidation of Q). In addition, we describe a new epitope in native (non-deamidated) gluten, QQPEQII (where E is gene encoded), which was associated with both B-cell and T-cell reactivity. By generating monoclonal antibodies from peptide-binding gut plasma cells of CeD patients, we show that antibodies to this native gluten epitope are cross-reactive with the major deamidated epitope due to recognition of the shared PEQ motif. Hence, antibodies to native gluten appear to arise from cross-reactive B cells that are generated as a side effect of the immune response to deamidated gluten. Since cross-reactive B cells could present peptides to different gluten-specific T cells, we suspect that such B cells can play a role in epitope spreading by engaging T cells with multiple specificities.
Architecture of home in later life: towards a fivefold theoretical model
Authors: Schaff Gwendoline , Petermans Ann , Vanrie Jan , Courtejoie Fabienne , Elsen Catherine 
Published: January 2022

PurposeMost older people wish to age “in place”. However, as current housing is mainly unsuitable for later life, architects have a key role to play. Yet, there is little architectural consideration for the notion of “ageing in place” and its various facets, beyond a functional focus. Architects seem to lack support to grasp inhabitants' sensible needs, and thus synergies with other human-centred disciplines could be enlightening. To ensure homes are designed in line with people's wellbeing, the authors aim to provide a state-of-the-art view, as to build a model supporting architects through their understanding of older people-environment relationships.Design/methodology/approachIn this paper, the authors investigate the key concepts that could enrich architects' design approaches on “ageing in place”. A narrative literature review scrutinising English- and French-written publications from the last twenty years in various disciplines was conducted, with a focus on older people and non-institutionalised housing.FindingsThe results highlight five essential perspectives to be taken into account when questioning housing for older people: health, affective, social, built and contextual perspectives. Their meaning and ties are developed and then synthesised into considerations, calling for architectural creativity.Originality/valueThis fivefold theoretical model adds to the existing architectural body of knowledge by adopting a multidisciplinary and multidimensional angle, going beyond the predominantly pragmatic vision associated with ageing. It provides stakeholders in architecture with a fresh and clear insight of meaningful relationships between older people and their residential environment.
Shape and topology optimal design problems in electromagnetic casting
Authors: Canelas Alfredo , Roche Jean Rodolphe 
Published: January 2022

PurposeIn this paper the authors review the recent numerical techniques proposed to solve the forward and inverse problems concerning the electromagnetic casting and electromagnetic levitation techniques of the metallurgical industry. In addition, the authors present a new topology optimization method to solve the inverse axisymmetric electromagnetic levitation problem.Design/methodology/approachThe proposed method is based on an exact second-order topological expansion of a Kohn–Vogelius-like functional specially devised for this problem.FindingsThrough some examples the authors show that it can find suitable solutions efficiently.Originality/valueThe new method completes the set of efficient methods available to solve the inverse electromagnetic casting and the inverse axisymmetric electromagnetic levitation problems.
Rohingyas and Sri Lankan Tamil refugees in Tamil Nadu: a replicable model of semi-permanent resettlement in low-resource settings
Authors: Radhakrishnan R.K. , de Wit Emma Emily , Gopikumar Vandana , Bunders Joske G.F. 
Published: January 2022

PurposeAfter being forced to flee their respective home countries, Sri Lankan Tamils and Rohingya refugees resettled in the Indian state of Tamil Nadu. This study attempts to explore the extent to which the state has provided means for integration in the absence of refugee protection laws and citizenship.Design/methodology/approachA qualitative research approach was used, including in-depth interviews (IDIs) and focus group discussions (FGDs) with participants from both refugee groups between 2019 and early 2020. A representative sample of male and female Sri Lankan Tamils, living in or outside government camps, in urban and rural areas, was included (total number = 75). Similarly, a representative sample of the Rohingya refugee community was included for this study (n = 44).FindingsDespite constraints imposed by inadequate infrastructure, the study finds that Sri Lankan Tamils and Rohingyas both show to be progressively integrated in local society and have been capable of fulfilling some important basic livelihood needs, especially with regards to education. Some areas for improvement are identified as well, most urgently in terms of health and accommodation.Practical implicationsOther states in India, as well as in similar low-income countries (LICs), could learn from the current case study with regards to administering workable policies for small groups of refugees.Originality/valueWith minimal state facilitation and within the context of limited legal backing, refugee groups have somewhat managed to re-built their lives. This study identifies the threshold of requirements that make this achievement possible and suggests what more could be done to further advance the current state.