bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell atlas of human oral mucosa reveals a stromal-neutrophil axis regulating tissue immunity in health and inflammatory disease
Authors: Williams DW , Greenwell- Wild T , Brenchley L , Dutzan N , Overmiller A , Sawaya AP , Webb S , Martin D , Hajishengallis G , Divaris K , Morasso M , Haniffa M , Moutsopoulos NM 
Published: April 2021

AbstractThe oral mucosa remains an understudied barrier tissue rich in exposure to antigens, commensals and pathogens. Moreover, it is the tissue where one of the most prevalent human microbe-triggered inflammatory diseases, periodontitis, occurs. To understand this complex environment at the cellular level, we assemble herein a human single-cell transcriptome atlas of oral mucosal tissues in health and periodontitis. Our work reveals transcriptional diversity of stromal and immune cell populations, predicts intercellular communication and uncovers an altered immune responsiveness of stromal cells participating in tissue homeostasis and disease at the gingival mucosa. In health, we define unique populations ofCXCL1,2,8-expressing epithelial cells and fibroblasts mediating immune homeostasis primarily through the recruitment of neutrophils. In disease, we further observe stromal, particularly fibroblast hyper-responsiveness linked to recruitment of leukocytes and neutrophil populations. Ultimately, a stromal-neutrophil axis emerges as a key regulator of mucosal immunity. Pursuant to these findings, most Mendelian forms of periodontitis were shown to be linked to genetic mutations in neutrophil and select fibroblast-expressed genes. Moreover, we document previously unappreciated expression of known pattern- and damage-recognition receptors on stromal cell populations in the setting of periodontitis, suggesting avenues for triggering stromal responses. This comprehensive atlas offers an important reference for in-depth understanding of oral mucosal homeostasis and inflammation and reveals unique stromal–immune interactions implicated in tissue immunity.
Visualizing the organization and differentiation of the male-specific nervous system ofC. elegans
Authors: Tekieli Tessa , Yemini Eviatar , Nejatbakhsh Amin , Varol Erdem , Fernandez Robert W. , Masoudi Neda , Paninski Liam , Hobert Oliver 
Published: April 2021

ABSTRACTSex differences in the brain are prevalent throughout the animal kingdom and particularly well appreciated in the nematodeC. elegans. While 294 neurons are shared between the two sexes, the nervous system of the male contains an additional 93 malespecific neurons, most of which have received very little attention so far. To make these neurons amenable for future study, we describe here how a multicolor, multipromoter reporter transgene, NeuroPAL, is capable of visualizing the distinct identities of all male specific neurons. We used this tool to visualize and characterize a number of features of the male-specific nervous system. We provide several proofs of concept for using NeuroPAL to identify the sites of expression ofgfp-taggedreporter genes. We demonstrate the usage of NeuroPAL for cellular fate analysis by analyzing the effect of removal of developmental patterning genes, including a HOX cluster gene (egl-5), a miRNA (lin-4) and a proneural gene (lin-32/Ato), on neuronal identity acquisition within the male-specific nervous system. We use NeuroPAL and its intrinsic cohort of more than 40 distinct differentiation markers to show that, even though male-specific neurons are generated throughout all four larval stages, they execute their terminal differentiation program in a coordinated manner in the fourth larval stage that is concomitant with male tale retraction. This wave of differentiation couples neuronal maturation programs with the appearance of sexual organs. We call this wave “just-in-time” differentiation by its analogy to the mechanism of “just-in-time” transcription of metabolic pathway genes.
Resurrecting self-cleaving mini-ribozymes from 40-million-year-old LINE-1 elements in human genome
Authors: Zhang Zhe , Xiong Peng , Wang Junfeng , Zhan Jian , Zhou Yaoqi 
Published: April 2021

AbstractLong Interspersed Nuclear Element (LINE) retrotransposons play an important role in genomic innovation as well as genomic instability in many eukaryotes including human. Random insertions and extinction through mutational inactivation make them perfectly time-stamped “DNA fossils”. Here, we investigated the origin of a self-cleaving ribozyme in 5’ UTR of LINE-1. We showed that this ribozyme only requires 35 nucleotides for self-cleavage with a simple but previously unknown secondary-structure motif that was determined by deep mutational scanning and covariation analysis. Structure-based homology search revealed the existence of this mini-ribozyme in anthropoids but not in prosimians. In human, the most homologs of this mini-ribozyme were found in lineage L1PA6-10 but essential none in more recent L1PA1-2 or more ancient L1PA13-15. We resurrected mini-ribozymes according to consensus sequences and confirmed that mini-ribozymes were active in L1PA10 and L1PA8 but not in L1PA7 and more recent lineages. The result paints a consistent picture for the emergence of the active ribozyme around 40 million years ago, just before the divergence of the new world monkeys (Platyrrhini) and old-world monkeys (Catarrhini). The ribozyme, however, subsequently went extinct after L1PA7 emerged around 30 million years ago with a deleterious mutation. This work uncovers the rise and fall of the mini-LINE-1 ribozyme recorded in the “DNA fossils” of our own genome. More importantly, this ancient, naturally trans-cleaving ribozyme (after removing the non-functional stem loop) may find its modern usage in bioengineering and RNA-targeting therapeutics.
Elucidating the crosstalk between inflammation and DNA damage pathways in the pancreatic beta-cell through the diabetes susceptibility gene,TCF19
Authors: Yang Grace H. , Fontaine Danielle A. , Lodh Sukanya , Blumer Joseph T. , Roopra Avtar S. , Davis Dawn Belt 
Published: April 2021

AbstractTCF19is a gene that is associated with both type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in genome-wide association studies. Prior studies have demonstrated that TCF19 knockdown impairs β-cell proliferation and increases apoptosis. However, little is known about its role in diabetes pathogenesis or the effects of TCF19 gain-of-function. The aim of this study was to examine the impact of TCF19 overexpression in INS-1 β-cells on proliferation and gene expression. With TCF19 overexpression, there was an increase in nucleotide incorporation without any change in cell cycle gene expression, alluding to an alternate process of nucleotide incorporation. Analysis of RNAseq of TCF19 overexpressing cells revealed increased expression of several DNA damage response (DDR) genes, as well as a tightly linked set of genes involved in cell stress, immune system processes, and inflammation. This connectivity between DNA damage and inflammatory gene expression has not been well studied in the β-cell, and suggests a novel role for TCF19 in regulating these pathways. Future studies determining how TCF19 may modulate these pathways may provide potential targets for β-cell survival.
Antibody responses induced by trivalent inactivated influenza vaccine among pregnant and non-pregnant women in Thailand: a matched cohort study
Authors: Nakphook Sutthichai , Patumanond Jayanton , Shrestha Manash , Prasert Kriengkrai , Chittaganpitch Malinee , Mott Joshua A. , Praphasiri Prabda 
Published: April 2021

AbstractBackgroundWe compared influenza antibody titers among vaccinated and unvaccinated pregnant and non-pregnant women.MethodsDuring 1st June – 30th September 2018, four groups of cohort participants - vaccinated pregnant, unvaccinated pregnant, vaccinated non-pregnant, and unvaccinated non-pregnant women were selected by matching age, gestational age, and the week of vaccination. Serum antibody titers against each strain of 2018 Southern Hemisphere inactivated trivalent influenza vaccine (IIV3) were assessed by hemagglutination inhibition (HI) assay on Day 0 (pre-vaccination) and Day 28 (one month post-vaccination) serum samples. Geometric mean titer (GMT), GMT ratio (GMR), seroconversion (defined as ≥4 fold increase in HI titer), and seroprotection (i.e. HI titer ≥1:40) were compared across the study groups using multilevel regression analyses, controlling for previous year vaccination from medical records and baseline antibody levels.ResultsA total of 132 participants were enrolled in the study (33 in each of the four study groups). The baseline GMTs were similar for influenza A(H1N1), A(H3N2), and B vaccine strains among all four groups (all p-values >0.05). After one month, both vaccinated groups had significantly higher GMT, GMR, seroconversion, and seroprotection than their unvaccinated controls (all p-values <0.05). The seroconversion rate was over 60% for any strain among the vaccinated groups, with the highest (88.8%) observed against A(H1N1) in the vaccinated pregnant group. Similarly, at least 75% of the vaccinated participants developed seroprotective antibody levels against all three strains; the highest seroprotection was found against A(H3N2) at 92.6% among vaccinated non-pregnant participants. Pregnant women had similar antibody responses (post-vaccination GMT, GMR, seroconversion, and seroprotection) to non-pregnant women for all three strains of IIV3 (all p>0.05).ConclusionsThe 2018 seasonal IIV3 was immunogenic against all three vaccine strains and pregnancy did not seem to alter the immune response to IIV3. These findings support the current influenza vaccination recommendations for pregnant women.
The MYB33, MYB65, and MYB101 transcription factors affect Arabidopsis and potato responses to drought by regulating the ABA signaling pathway
Authors: Wyrzykowska Anna , Bielewicz Dawid , Plewka Patrycja , Sołtys-Kalina Dorota , Wasilewicz-Flis Iwona , Marczewski Waldemar , Jarmolowski Artur , Szweykowska-Kulinska Zofia 
Published: April 2021

AbstractAimsDrought is a climate threat limiting crop production. Potato is one of the four most important food crops worldwide and is sensitive to water shortage. The CBP80 gene was shown to affect plant response to drought by regulating the level of microRNA159, and, consequently, the levels of the MYB33 and MYB101 transcription factors. (TF) Our studies aimed to show whether indeed the level of MYB33, MYB65, and MYB101 TFs affects plant response to water shortage.MethodsArabidopsis transgenic plants exhibiting downregulation and Arabidopsis and potato transgenic plants exhibiting overexpression of selected MYB TFs were obtained. Plants response to drought was mainly measured using relative water content (RWC) and stomata closure upon exogenous ABA.ResultsThree MYB TFs studied are involved in plant response to drought. When downregulated in Arabidopsis, the MYB33, MYB65 and MYB101 genes cause stomatal hyposensitivity to ABA, leading to reduced tolerance to drought. Transgenic Arabidopsis and potato plants overexpressing a mutated version of these genes with changed miR159 recognition site, show hypersensitivity to ABA and relatively high tolerance to drought conditions.ConclusionsThe MYB33, MYB65, and MYB101 genes are good be potential targets for innovative breeding to obtain crops with relatively high tolerance to drought.
Charting human subcortical maturation across the adult lifespan within vivo7 T MRI
Authors: Miletić Steven , Bazin Pierre-Louis , Isherwood Scott J. S. , Keuken Max C. , Alkemade Anneke , Forstmann Birte U. 
Published: April 2021

AbstractThe human subcortex comprises hundreds of unique structures. Subcortical functioning is crucial for behavior, and disrupted function is observed in common neurodegenerative diseases. Despite their importance, human subcortical structures continue to be difficult to studyin vivo. Here we provide a detailed account of 17 prominent subcortical structures, describing their approximate iron and myelin contents, morphometry, and their age-related changes across the normal adult lifespan. The results provide compelling insights into the heterogeneity and intricate age-related alterations of these structures. They also show that the locations of many structures shift across the lifespan, which is of direct relevance for the use of standard magnetic resonance imaging atlases. The results further our understanding of subcortical morphometry and neuroimaging properties, and of normal aging processes which ultimately can improve our understanding of neurodegeneration.
Rab10 regulates the sorting of internalised TrkB for retrograde axonal transport
Authors: Lazo Oscar M. , Schiavo Giampietro 
Published: April 2021

AbstractNeurons process real-time information from axon terminals to coordinate gene expression, growth and plasticity. Input from distal axons is encoded as a stream of endocytic organelles, termed signalling endosomes, targeted to the soma. Formation of these organelles depends on target-derived molecules, such as brain-derived neurotrophic factor (BDNF), which is recognised by TrkB receptors on the plasma membrane, endocytosed and transported to the cell body along the microtubules network. Notwithstanding its neuropathological importance, the mechanism controlling the sorting of TrkB to signalling endosomes is currently unknown. In this work, we uncover the small GTPase Rab10 as critical for TrkB sorting and propagation of BDNF signalling from axon terminals to the soma. Our data demonstrate that Rab10 defines a novel class of axonal organelles, rapidly mobilised towards the axon terminal upon BDNF stimulation, enabling the axon to fine-tune retrograde signalling depending on BDNF availability at the synapse. These results help clarifying the neuroprotective phenotype recently associated to Rab10 polymorphisms and provide a new therapeutic target to halt neurodegeneration.
Myeloid and endothelial cells cooperate to promote hematopoietic stem cells expansion in the fetal niche
Authors: Cacialli Pietro , Mailhe Marie-Pierre , Golub Rachel , Bertrand Julien Y. 
Published: April 2021

AbstractDuring embryonic development, very few hematopoietic stem cells (HSCs) are produced from the hemogenic endothelium, that will be expanded in a very specific niche. This fetal HSC niche comprises a complex and dynamic molecular network of interactions between multiple cell types, including endothelial cells (ECs) and mesenchymal stromal cells. It is known that functional changes in the hematopoietic niche, such as aging, vascular cell remodelling or inflammation can directly affect HSCs. Among all these inflammatory regulators, the eicosanoid prostaglandin E (PGE2) has been shown to be very important during embryonic life. However, the precise source of PGE2 in the embryo is still elusive. Here we show that all the genes involved in PGE2 synthesis and transport are expressed by distinct cells of the caudal hematopoietic tissue (CHT) in the zebrafish embryo and in the mouse fetal liver, suggesting that each cell type acts sequentially and collaboratively with the others to produce PGE2 and ultimately expand HSCs. Among these cells, we found myeloid cells (both neutrophils and macrophages) to be absolutely necessary, as they concur to the production of PGH2, the precursor of PGE2. To measure the impact of myeloid cells, we generated a genetic model of myeloid ablation, which caused a loss of HSCs in the CHT, that could be rescued by supplementing zebrafish embryos with PGE2 or PGH2. ECs expressed theslco2b1transporter to import PGH2, andptges3, the necessary enzyme to convert this latter into PGE2. Taken altogether, our data show that the triad composed of neutrophils, macrophages and ECs concurs to HSC expansion in the CHT.
CD95 expression in triple negative breast cancer blocks induction of an inflammatory state through differential regulation of NF-κB Signaling
Authors: Guégan Jean-Philippe , Pollet Justine , Ginestier Christophe , Charafe-Jauffret Emmanuelle , Peter Marcus E. , Legembre Patrick 
Published: April 2021

AbstractCD95L is expressed by tumor-infiltrating lymphocytes to eliminate CD95-expressing tumor cells and thereby CD95 loss by tumor cells is often considered as a consequence of an immunoediting process. Nonetheless CD95 expression is maintained in most triple negative breast cancers (TNBCs), and we recently reported that CD95 loss in TNBC cells triggers the induction of a pro-inflammatory program promoting the recruitment of cytotoxic NK and CD8+ T-cells and impairing tumor growth. Using a comprehensive proteomic approach, we have identified two yet unknown CD95 interaction partners, Kip1 ubiquitination-promoting complex protein 2 (KPC2) and p65. KPC2 contributes to the partial degradation of p105 (NFκB1) and the subsequent generation of p50 homodimers, which transcriptionally represses pro-inflammatory NF-κB-driven gene expression. Mechanistically, KPC2 directly interacts with the C-terminal region of CD95 and links the receptor to RelA (p65) and KPC1, the catalytic subunit of the KPC complex that acts as E3 ubiquitin-protein ligase promoting the partial degradation of p105 into p50. Loss of CD95 in TNBC cells releases KPC2, limiting the formation of the NF-κB inhibitory homodimer complex (p50/p50), promoting NF-κB activation and the production of pro-inflammatory cytokines including CSF1, CSF2, CXCL1 and IL1 members, known to promote recruitment and differentiation of certain adaptive and innate immune effector cells.
Somite morphogenesis is required for axial blood vessel formation
Authors: Paulissen Eric , Palmisano Nicholas J. , Waxman Joshua , Martin Benjamin L. 
Published: April 2021

ABSTRACTAngioblasts that form the major axial blood vessels of the dorsal aorta and cardinal vein migrate towards the embryonic midline from distant lateral positions. Little is known about what controls the precise timing of angioblast migration and their final destination at the midline. Using zebrafish, we found that midline angioblast migration requires neighboring tissue rearrangements generated by somite morphogenesis. The somitic shape changes cause the adjacent notochord to separate from the underlying endoderm, creating a ventral midline cavity that provides a physical space for the angioblasts to migrate into. The anterior to posterior progression of midline angioblast migration is facilitated by retinoic acid induced anterior to posterior somite maturation and the subsequent progressive opening of the ventral midline cavity. Our work demonstrates a critical role for somite morphogenesis in organizing surrounding tissues to facilitate notochord positioning and angioblast migration, which is ultimately responsible for creating a functional cardiovascular system.Summary statementRetinoic acid induced somite morphogenesis generates a midline cavity that accommodates migrating angioblasts, which form the axial blood vessels.
Actuator model for spacecraft attitude control simulation
Authors: Zhang Chengxi , Wu Jin , Sun Ran , Wang Mingjiang , Ran Dechao 
Published: April 2021

Purpose
The purpose of this paper is to study the general actuator modeling in spacecraft attitude control systems.

Design/methodology/approach
The proposed module in this paper provides various non-ideal factors such as the second-order dynamic time response, time-delay, bias torques, dead-zones and saturation. The actuator module can make the simulation as close to the practical situation as possible.

Findings
This paper presents a practical integrated module for the simulation of attitude control algorithms. Based on theoretical modeling, we give simulation modules and numerical examples. The proposed model can be directly used in spacecraft control simulation. Instead of considering only a few of them, it makes the simulation more convincing. Though it may not be perfect, it is better than totally ignoring the actuator dynamics.

Originality/value
The authors provide an integrated actuator model for spacecraft attitude control simulation, considering as many nonlinear factors as possible once time.
Optimization of profitability and liquidity for residential projects under debt and equity financing
Authors: Cevikcan Emre , Kose Yildiz 
Published: April 2021

PurposeAn appropriate space allocation among different residence types gives higher profitability and liquidity for cash flow management in real estate projects for developers. Thereby, a balance between debt and equity should be kept for capital formation in developers where high level of cost, profit and risk exists. The purpose of this paper is to provide cash flow optimization under debt and equity financing while providing an appropriate space allocation of residence types via synchronous consideration of profitability and liquidity.Design/methodology/approachA novel optimization methodology that includes project financing, optimization and experimental design modules is proposed. The first module, project financing, considers the flexibility of utilizing one or both of debt financing and equity financing when making capital. The optimization module addresses space allocation among different residence types for a construction while maximizing profitability and liquidity using two mixed-integer linear programming models in a pre-emptive manner. The experimental design module assesses the effects of decisive parameters within the methodology via multivariate analysis of variance (MANOVA).FindingsThe proposed methodology is applied to a real-life residential project in Istanbul. The optimization module yielded 42.5% profitability via the first linear programming model and 2.2% trade-off between liquidity and profitability while minimizing the payback period by the second linear programming model. Meanwhile, MANOVA results showed that profit per square meter and sale rate trends are the most prominent factors considering their significant effects on net present value and payback period.Originality/valueTo the best knowledge of the author, related papers focused only on profitability under equity financing. Liquidity (as an objective) and equity financing (as a financing method) have not been handled. Hence, this paper not only performs profitability and liquidity-oriented cash flow optimization under debt and equity financing but also optimizes space allocation of residences for the first time.
Changing the layout of farmers markets can affect cross-contamination
Authors: Acosta Karla M. , Mohammad Zahra H. , Yu Heyao , Kirkwood Kristen , Gibson Kristen , Neal Jack A. , Sirsat Sujata A. 
Published: April 2021

PurposeThe purpose of this study was to investigate whether the layout has an effect on cross-contaminations levels at farmers markets.Design/methodology/approachWe used social cognitive theory's triadic reciprocity model to investigate how influencing the environment could change the behaviors of farmers’ market consumers and reduce the risk of microbial cross-contamination using a Fluorescent Compound (FC). For this purpose, a 3 × 2 experimental between-subject factorial design was utilized in this study: three farmers market layouts (i.e. U-shaped [U-S], L-shaped [L-S] and square-shaped [S–S]) and two different set-ups per market (i.e. produce and non-produce vendors completely separated, and alternating produce and non-produce vendors). FC was utilized to simulate microbial contamination on the participants (n = 54) hands. The participants were allowed to walk through the layout for 3 min and touch items after which a total of 475 swab samples were processed and recorded for absorbance levels.FindingsThe results indicated that the cross-contamination level of the U-S market was significantly lower (p < 0.001) than those of the L-S and S–S markets. The best market layout and set-up based on the average levels of simulated cross-contamination were the U-S market, particularly with the A set-up, where produce and non-produce booths were scattered.Originality/valueThis study is the first to use the quantification of FC to identify the impact of a farmers’ market layout/design on cross-contamination levels. These results can be used to provide guidance to market managers on layout and design from a safety standpoint to reduce the risk of cross-contamination.