bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mast cells can produce transforming growth factor β1 and promote tissue fibrosis during the development of Sjögren’s syndrome-related sialadenitis
Authors: Kaieda Shinjiro , Fujimoto Kyoko , Todoroki Keita , Abe Yushi , Kusukawa Jingo , Hoshino Tomoaki , Ida Hiroaki 
Published: October 2021

ABSTRACT

Objectives
This study investigated the associations of mast cells with immune-mediated inflammation and fibrosis in patients with primary Sjögren’s syndrome (pSS); it also explored the underlying pathophysiology of pSS-related sialadenitis.

Methods
Twenty-two patients with pSS and 10 patients with sicca (control individuals) underwent labial salivary gland biopsies. Sections were subjected to staining and immunofluorescence analyses. HMC-1 human mast cells were cocultured with fibroblasts in vitro; fibroblasts were also grown in HMC-1 conditioned medium. mRNA levels of collagen Type I (Col1a) and transforming growth factor (TGF)β1 were analysed in cultured cells.

Results
Mast cell numbers in labial salivary glands were significantly greater in patients with pSS than in control individuals. In salivary glands from patients with pSS, mast cell number was significantly correlated with fibrosis extent; moreover, mast cells were located near fibrous tissue and expressed TGFβ1. Col1a and TGFβ1 mRNAs were upregulated in cocultured fibroblasts and HMC-1 cells, respectively. Fibroblasts cultured in HMC-1 conditioned medium exhibited upregulation of Col1a mRNA; this was abrogated by TGFβ1 neutralizing antibodies.

Conclusions
Mast cell numbers were elevated in patients with pSS-related sialadenitis; these cells were located near fibroblasts and expressed TGFβ1. TGFβ1 could induce collagen synthesis in fibroblasts, which might contribute to fibrosis.
A set of accessible enhancers enables the initial response of breast cancer cells to physiological progestin concentrations
Authors: Zaurin Roser , Ferrari Roberto , Nacht Ana Silvina , Carbonell Jose , Le Dily Francois , Font-Mateu Jofre , de Llobet Cucalon Lara Isabel , Vidal Enrique , Lioutas Antonios , Beato Miguel , Vicent Guillermo P 
Published: October 2021

Abstract
Here, we report that in T47D breast cancer cells 50 pM progestin is sufficient to activate cell cycle entry and the progesterone gene expression program. At this concentration, equivalent to the progesterone blood levels found around the menopause, progesterone receptor (PR) binds only to 2800 genomic sites, which are accessible to ATAC cleavage prior to hormone exposure. These highly accessible sites (HAs) are surrounded by well-organized nucleosomes and exhibit breast enhancer features, including estrogen receptor alpha (ERα), higher FOXA1 and BRD4 (bromodomain containing 4) occupancy. Although HAs are enriched in RAD21 and CTCF, PR binding is the driving force for the most robust interactions with hormone-regulated genes. HAs show higher frequency of 3D contacts among themselves than with other PR binding sites, indicating colocalization in similar compartments. Gene regulation via HAs is independent of classical coregulators and ATP-activated remodelers, relying mainly on MAP kinase activation that enables PR nuclear engagement. HAs are also preferentially occupied by PR and ERα in breast cancer xenografts derived from MCF-7 cells as well as from patients, indicating their potential usefulness as targets for therapeutic intervention.
Phospho-Ku70 induced by DNA damage interacts with RNA Pol II and promotes the formation of phospho-53BP1 foci to ensure optimal cNHEJ
Authors: Schellenbauer Amelie , Guilly Marie-Noelle , Grall Romain , Le Bars Romain , Paget Vincent , Kortulewski Thierry , Sutcu Haser , Mathé Cécile , Hullo Marie , Biard Denis , Leteurtre François , Barroca Vilma , Corre Youenn , Irbah Lamya , Rass Emilie , Theze Benoit , Bertrand Pascale , Demmers Jeroen A A , Guirouilh-Barbat Josée , Lopez Bernard S , Chevillard Sylvie , Delic Jozo 
Published: October 2021

AbstractCanonical non-homologous end-joining (cNHEJ) is the prominent mammalian DNA double-strand breaks (DSBs) repair pathway operative throughout the cell cycle. Phosphorylation of Ku70 at ser27-ser33 (pKu70) is induced by DNA DSBs and has been shown to regulate cNHEJ activity, but the underlying mechanism remained unknown. Here, we established that following DNA damage induction, Ku70 moves from nucleoli to the sites of damage, and once linked to DNA, it is phosphorylated. Notably, the novel emanating functions of pKu70 are evidenced through the recruitment of RNA Pol II and concomitant formation of phospho-53BP1 foci. Phosphorylation is also a prerequisite for the dynamic release of Ku70 from the repair complex through neddylation-dependent ubiquitylation. Although the non-phosphorylable ala-Ku70 form does not compromise the formation of the NHEJ core complex per se, cells expressing this form displayed constitutive and stress-inducible chromosomal instability. Consistently, upon targeted induction of DSBs by the I-SceI meganuclease into an intrachromosomal reporter substrate, cells expressing pKu70, rather than ala-Ku70, are protected against the joining of distal DNA ends. Collectively, our results underpin the essential role of pKu70 in the orchestration of DNA repair execution in living cells and substantiated the way it paves the maintenance of genome stability.
Real-time tracking of ER turnover during ERLAD by a rhenium complex via lifetime imaging
Authors: Hao Liang , Ling Yu-Yi , Huang Zhi-Xin , Pan Zheng-Yin , Tan Cai-Ping , Mao Zong-Wan 
Published: October 2021

AbstractEndoplasmic reticulum (ER) degradation by autophagy (ER-phagy) is a recently revealed selective autophagy pathway that plays important roles in organelle turnover and protein degradation, but the biological functions of ER-phagy are largely unknown. Here, we present an ER-targeting Re(I) tricarbonyl complex (Re-ERLAD) that can accumulate in the ER, induce ER-to-lysosome-associated degradation (ERLAD) upon visible light irradiation, and label ER buds and track their morphological alterations during ER-phagy. The emission of Re-ERLAD is sensitive to viscosity, which is a key parameter reflecting the amount of unfolded protein in the ER. Quantitative detection using two-photon fluorescence lifetime imaging microscopy shows that ER viscosity initially increases and then decreases during ERLAD, which reveals that ERLAD is a pathway for alleviating ER stress caused by unfolded proteins. In conclusion, our work presents the first specific photoinducer and tracker of ERLAD, which can be used in studying the regulatory mechanism and function of this process.
A Better Way to Measure Climate Footprints
Authors: Gordon Deborah 
Published: October 2021

Abstract
Chapter 3 presents the Oil Climate Index plus Gas (OCI+), the first open-source tool that assesses and compares the different climate effects of the wide range of oils produced around the world, taking into account upstream, midstream, and downstream emissions. The chapter walks through the motivation behind creating the OCI+ with collaborators from Stanford University and the University of Calgary. The underlying models composing the OCI+ are discussed and visualized in detail. Model data and uncertainty are fleshed out. The chapter discusses methods for evaluating OCI+ emissions using remote sensing, satellites that spot flares from space, and an expanding array of methane measurement instruments. Possible avenues to build out the OCI+ to include other air pollutants are presented. The chapter concludes by laying out estimated ranges of currently modeled emissions intensities of global oil and gas supplies.
Generalized local ansatz for scale-dependent primordial non-Gaussianities and future galaxy surveys
Authors: Yamauchi Daisuke , Yokoyama Shuichiro , Takahashi Tomo 
Published: October 2021

Abstract
We revisit a possible scale-dependence of local-type primordial non-Gaussianities induced by super-horizon evolution of scalar field perturbations. We develop the formulation based on δN formalism and derive the generalized form of the local-type bispectrum and also trispectrum which allows us to implement the scale-dependence and suitably compare model prediction with observational data. We propose simple but phenomenologically meaningful expressions, which encompass the information of a wide range of physically motivated models. We also formulate a large-scale power spectrum and bispectrum of biased objects in the presence of the scale-dependent primordial non-Gaussianities. We perform the Fisher analysis for future galaxy surveys and give the projected constraints on the parameters of the generalized local-form of primordial non-Gaussianities.
In Planta Cell Wall Engineering: From Mutants to Artificial Cell Walls
Authors: Yoshida Kouki , Sakamoto Shingo , Mitsuda Nobutaka 
Published: October 2021

AbstractTo mitigate the effects of global warming and to preserve the limited fossil fuel resources, an increased exploitation of plant-based materials and fuels is required, which would be one of the most important innovations related to sustainable development. Cell walls account for the majority of plant dry biomass and so is the target of such innovations. In this review, we discuss recent advances in in planta cell wall engineering through genetic manipulations, with a focus on wild-type-based and mutant-based approaches. The long history of using a wild-type-based approach has resulted in the development of many strategies for manipulating lignin, hemicellulose and pectin to decrease cell wall recalcitrance. In addition to enzyme-encoding genes, many transcription factor genes important for changing relevant cell wall characteristics have been identified. Although mutant-based cell wall engineering is relatively new, it has become feasible due to the rapid development of genome-editing technologies and systems biology–related research; we will soon enter an age of designed artificial wood production via complex genetic manipulations of many industrially important trees and crops.
miR169q and NUCLEAR FACTOR YA8 enhance salt tolerance by activating PEROXIDASE1 expression in response to ROS
Authors: Xing Lijuan , Zhu Ming , Luan Mingda , Zhang Min , Jin Lian , Liu Yueping , Zou Junjie , Wang Lei , Xu Miaoyun 
Published: October 2021

Abstract
Salt stress signiﬁcantly reduces the productivity of crop plants including maize (Zea mays). miRNAs are major regulators of plant growth and stress responses, but few studies have examined the potential impacts of miRNAs on salt stress responses in maize. Here, we show that ZmmiR169q is responsive to stress-induced ROS signals. After detecting that salt stress and exogenous H2O2 treatment reduced the accumulation of ZmmiR169q, stress assays with transgenic materials showed that depleting ZmmiR169q increased seedling salt tolerance whereas overexpressing ZmmiR169q decreased salt tolerance. Helping explain these observations, we found that ZmmiR169q repressed the transcript abundance of its target NUCLEAR FACTOR YA8 (ZmNF-YA8), and overexpression of ZmNF-YA8 in maize improved salt tolerance, specifically by transcriptionally activating the expression of the efficient antioxidant enzyme PEROXIDASE1. Our study reveals a direct functional link between salt stress and a miR169q-NF-YA8 regulatory module that plants use to manage ROS stress and strongly suggests that ZmNF-YA8 can be harnessed as a resource for developing salt-tolerant crop varieties.
Strigo-D2—a bio-sensor for monitoring spatio-temporal strigolactone signaling patterns in intact plants
Authors: Song Changzheng , Zhao Jiao , Guichard Marjorie , Shi Dongbo , Grossmann Guido , Schmitt Christian , Jouannet Virginie , Greb Thomas 
Published: October 2021

Abstract
Strigolactones (SLs) are a class of plant hormones that mediate biotic interactions and modulate developmental programs in response to endogenous and exogenous stimuli. However, a comprehensive view on the spatio-temporal pattern of SL signaling has not been established, and tools for a systematic in planta analysis do not exist. Here, we present Strigo-D2, a genetically encoded ratiometric SL signaling sensor that enables the examination of SL signaling distribution at cellular resolution and is capable of rapid response to altered SL levels in intact Arabidopsis (Arabidopsis thaliana) plants. By monitoring the abundance of a truncated and fluorescently labeled SUPPRESSOR OF MAX2 1-LIKE 6 (SMXL6) protein, a proteolytic target of the SL signaling machinery, we show that all cell types investigated have the capacity to respond to changes in SL levels but with very different dynamics. In particular, SL signaling is pronounced in vascular cells but low in guard cells and the meristematic region of the root. We also show that other hormones leave Strigo-D2 activity unchanged, indicating that initial SL signaling steps work in isolation from other hormonal signaling pathways. The specificity and spatio-temporal resolution of Strigo-D2 underline the value of the sensor for monitoring SL signaling in a broad range of biological contexts with highly instructive analytical depth.
Can Central Sensitization After Injury Persist as an Autonomous Pain Generator? A Comprehensive Search for Evidence
Authors: Brazenor Graeme A , Malham Gregory M , Teddy Peter J 
Published: October 2021

Abstract

Objective
To conduct a comprehensive search for evidence with regard to whether central sensitization after an injury can act as a persistent autonomous pain generator after the inducing injury has healed.

Methods
We searched Medline on PubMed and the Cochrane Library, screening 3,572 abstracts, from which 937 full-text articles were obtained, with 186 of these discarded as irrelevant to the question being posed. The remaining 751 articles were studied for evidence.

Results
Fourteen publications were judged to provide weak evidence for the hypothesis of central sensitization as a persisting autonomous pain generator, but none addressed the question directly. No strong evidence for the affirmative answer was found. Sixty-one publications were judged to provide weak evidence for a negative answer, and ten were judged to provide strong evidence. Unexpectedly, serious weaknesses were discovered in the literature underpinning the validity of the clinical diagnosis of central sensitization in humans: 1) inappropriate extrapolation, in many publications, of laboratory animal data to humans; 2) failure to demonstrate the absence of peripheral pain generators that might be perpetuating central sensitization; and 3) many factors now shown to confound what is being measured by quantitative sensory testing, conditioned pain modulation, and the Central Sensitization Inventory.

Conclusions
We found no evidence proving that central sensitization can persist as an autonomous pain generator after the initiating injury has healed. Our review has also shown that the evidential basis for the diagnosis of central sensitization in individual patients is seriously in question.
Tensor network approach to two-dimensional Yang–Mills theories
Authors: Fukuma Masafumi , Kadoh Daisuke , Matsumoto Nobuyuki 
Published: October 2021

Abstract
We propose a novel tensor network representation for two-dimensional Yang–Mills theories with arbitrary compact gauge groups. In this method, tensor indices are given directly by group elements with no direct use of the character expansion. We apply the tensor renormalization group method to this tensor network for SU(2) and SU(3), and find that the free energy density and the energy density are accurately evaluated. We also show that the singular value decomposition of a tensor has a group-theoretic structure and can be associated with the character expansion.
Evidence on Job Search Models from a Survey of Unemployed Workers in Germany
Authors: DellaVigna Stefano , Heining Jörg , Schmieder Johannes F , Trenkle Simon 
Published: October 2021

Abstract
The job-finding rate of unemployment insurance (UI) recipients declines in the initial months of unemployment and then exhibits a spike at the benefit exhaustion point. A range of theoretical explanations have been proposed, but those are hard to disentangle using data on job finding alone. To better understand the underlying mechanisms, we conducted a large text-message-based survey of unemployed workers in Germany. We surveyed 6,349 UI recipients twice a week for four months about their job search effort. The panel structure allows us to observe how search effort evolves in individuals over the unemployment spell. We provide three key facts: (i) search effort is flat early on in the UI spell, (ii) search effort exhibits an increase up to UI exhaustion and a decrease thereafter, (iii) UI recipients do not appear to time job start dates to coincide with the UI exhaustion point. A standard search model with unobserved heterogeneity struggles to explain the second fact, and a model of storable offers is not consistent with the third fact. The patterns are well captured by a model of reference-dependent job search or by a model with duration dependence in search cost.
Patent Screening, Innovation, and Welfare
Authors: Schankerman Mark , Schuett Florian 
Published: October 2021

Abstract
Critics claim that patent screening is ineffective, granting low-quality patents that impose unnecessary social costs. We develop an integrated framework, involving patent office examination, fees, and endogenous validity challenges in the courts, to study patent screening both theoretically and quantitatively. In our model, some inventions require the patent incentive while others do not, and asymmetric information creates a need for screening. We show that the endogeneity of challenges implies that courts, even if perfect, cannot solve the screening problem. Simulations of the model, calibrated on U.S. data, indicate that screening is highly imperfect, with almost half of all patents issued on inventions that do not require the patent incentive. While we find that the current patent system generates positive social value, intensifying examination would yield large welfare gains. The social value of the patent system would also be larger if complemented by antitrust limits on licensing.
Body composition in long-standing juvenile dermatomyositis: associations with disease activity, muscle strength and cardiometabolic measures
Authors: Witczak Birgit Nomeland , Bollerslev Jens , Godang Kristin , Schwartz Thomas , Flatø Berit , Molberg Øyvind , Sjaastad Ivar , Sanner Helga 
Published: October 2021

Abstract

Objective
To compare body composition parameters in patients with long-standing JDM and controls and to explore associations between body composition and disease activity/inflammation, muscle strength, health-related quality of life (HRQoL) and cardiometabolic measures.

Methods
We included 59 patients (median disease duration 16.7 y; median age 21.5 y) and 59 age- and sex-matched controls in a cross-sectional study. Active and inactive disease were defined by the PRINTO criteria. Body composition was assessed by total body DXA, inflammation by high-sensitivity CRP (hs-CRP) and cytokines, muscle strength by the eight-muscle manual muscle test, HRQoL by the 36-item Short Form Health Survey physical component score and cardiometabolic function by echocardiography (systolic and diastolic function) and serum lipids.

Results
DXA analyses revealed lower appendicular lean mass index (ALMI; reflecting limb skeletal muscle mass), higher body fat percentage (BF%) and a higher android fat:gynoid fat (A:G) ratio (reflecting central fat distribution) in patients than controls, despite similar BMI. Patients with active disease had lower ALMI and higher BF% than those with inactive disease; lower ALMI and higher BF% were associated with inflammation (elevated monocyte attractant protein-1 and hs-CRP). Lower ALMI was associated with reduced muscle strength, while higher BF% was associated with impaired HRQoL. Central fat distribution (higher A:G ratio) was associated with impaired cardiac function and unfavourable serum lipids.

Conclusion
Despite normal BMI, patients with JDM, especially those with active disease, had unfavourable body composition, which was associated with impaired HRQoL, muscle strength and cardiometabolic function. The association between central fat distribution and cardiometabolic alterations is a novel finding in JDM.
Mitochondrial DNA genetic variants are associated with systemic lupus erythematosus susceptibility, glucocorticoids efficacy and prognosis
Authors: Teng Ying , Yan Zi-Ye , Wang Lin-Lin , Wang Yu-Hua , Zhang Ting-Yu , Li Zhen , Liu Shuang , Cai Jing , Chen Yang-Fan , Li Mu , Liu Sheng-Xiu , Xu Zhou-Zhou , Huang Hai-Liang , Wang Fang , Pan Fa-Ming , Pan Hai-Feng , Su Hong , Zou Yan-Feng 
Published: October 2021

Abstract

Objective
To investigate the associations of mitochondrial DNA (mtDNA) genetic variants with SLE susceptibility, glucocorticoid (GC) efficacy and prognosis.

Methods
Our study was done in two stages. First, we performed whole mitochondrial genome sequencing in 100 patients and 100 controls to initially screen potential mtDNA variants associated with disease and GC efficacy. Then, we validated the results in an independent set of samples. In total, 605 SLE patients and 604 normal controls were included in our two-stage study. A two-stage efficacy study was conducted in 512 patients treated with GCs for 12 weeks. We also explored the association between mtDNA variants and SLE prognosis.

Results
In the combined sample, four mtDNA variants (A4833G, T5108C, G14569A, CA514-515-) were associated with SLE susceptibility (all PBH &lt; 0.05). We confirmed that T16362C was related to efficacy of GCs (PBH = 0.014). Significant associations were detected between T16362C and T16519C and the efficacy of GCs in females with SLE (PBH &lt; 0.05). In the prognosis study, variants A4833G (PBH = 0.003) and G14569A (PBH = 9.744 × 10−4) substantially increased SLE relapse risk. Female patients harbouring variants T5108C and T16362C were more prone to relapse (PBH &lt; 0.05). Haplotype analysis showed that haplogroup G was linked with SLE susceptibility (PBH = 0.001) and prognosis (PBH = 0.013). Moreover, mtDNA variant–environment interactions were observed.

Conclusion
We identified novel mtDNA genetic variants that were associated with SLE susceptibility, GC efficacy, and prognosis. Interactions between mtDNA variants and environmental factors were related to SLE risk and GC efficacy. Our findings provide important information for future understanding of the occurrence and development of SLE.