bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomimicry of greater club rush (Scirpus grossus L.f) and water mimosa (Neptunia oleracea Lour): Wetland plants inspiring innovative modular design
Authors: Krisdianto  , Haryanti N H , Susilawati I O
Published: February 2022

Intersection of three, terrestrial, aerial and aquatic ecosystems create a rich biodiversity and abundance ecosystem services, wetlands. A study of the Greater Club Rush and Water Mimosa, which are aquatic plants, as provision services has grown well and mosaic ornamented in shallow swampy land, has been carried out in 2021. This research aims to elucidate those plants capability to adapt of flooding situation and may inspire us about basic industrial prototyping products. For those, we calculate population density, basal area, height, biomass, bending moment and cut the stalk section to find out multi-folded a stalk like-stem. Also, we measure the length of leaves and weight of aerenchyma. The result shows the stalk of the Greater Club Rush is very possible to stand still to reduce the speed of flooding water, and Mimosa capability to floating it stem and branches as guaranty for photosynthesis in high tide water. In conclusion, those two plants have strongly possibility to adapt in flooding condition and inspiring us as a natural master copy of floating creative industrial modular designs to overcome the fluctuation of water level in the era of climate change, multi-folded walls and Tsunami floating capsules.
Trachea features and fiber dimensions of fast-growing tree: A case study on wood samples from eastern Indonesia
Authors: Dewi A P , Tihurua E F , Wulansari T Y I
Published: February 2022

Fast-growing plant is one of the characteristics of pioneer plants. Commonly, the plants grow in areas that is exposed to sunlight such as open area and forest edges. Fast-growing plants have different anatomical and physical wood characteristics compare with slow-growing plants. Therefore, this study aims to examine the anatomical characteristics of fast-growing plants, especially trees, namely the fiber cells and trachea features. A total of 33 wood samples from 28 species were used in this study. We used wood samples from Eastern Indonesia deposited at Herbarium Bogoriense. Examined wood samples are taken from branches with 1-2 cm of diameter. The anatomical characters observed were focused on two types of cells, namely fiber cells (fiber length, fiber diameter, fiber cell wall thickness, lumen width, identification of septate fibers and fibers pit) and the trachea (perforation type, pit arrangement, and pit form). From the observations of all wood samples showed that the length of fiber cells are classified as short (18 species) and medium (10 species) fiber. There are two groups of fiber cell wall thickness viz. very thin (16 species) and thin to thick (12 species). Septate fibers only found in 7 species especially Chisocheton and Teijsmanniodendron. Fiber’s pit observed in Horsfieldia parviflora, Mallotus peltatus, dan Neuburgia corynocarpa. All species have simple tracheal perforation with alternate or opposite pit arrangement. Moreover, branch wood samples have polygonal pit shape, oval or combination of those two shapes were found in some species, such as Horsfieldia parviflora, Sandoricum koetjape and Teijsmanniodendron bogoreinse.
Size doesn’t matter shape does: A morphological study of pitcher plant in distinct forest canopy structures
Authors: Harapan T S , Ikhwan A , Amolia R R , Zulaspita W , Ferbriamansyah T A , Bibas E , Sakdiah H T , Diniyati F , Mutashim M , Chairul C , Taufiq A , Nurainas N
Published: February 2022

Light exposure from the sun is the most crucial variable for producing optimal pitcher size and colour variation in Nepenthes. This study aimed to observe the effect of forest canopy structure on morphological character of Nepenthes ampullaria’s pitcher parts (longitudinal, front, and peristome) both on size and shape using Geometric morphometric (GM) approach and its prey diversity. We classified the forest canopy structure into two categories: inside the canopy and open space area (gap). We used Unmanned Aerial Vehicle (UAV) images to build Canopy Height Model (CHM). Then, ForestGapR R package used to analyse and generated the forest gaps area. The prey specimens and photograph samples comprised from 9 individuals with three lower pitchers in open space area with high light exposure as well as shaded area inside the canopy. Total of 54 images were marked by point and curve to generated a landmark analysis using GeoMorph R package. Based on GM analysis, we observed that the forest canopy structure could affect Nepenthes pitcher shape but not in pitcher size. Our field result revealed Nepenthes ampullaria likely dominated by darker colour with a red spot in the shaded area and bright green colour in the open. However, based on our study the pitcher in shaded area inside the canopy have a larger number of prey species than the open area.
Analysis of the mechanical properties and microstructure of titanium surfaces designed by electromagnetic induction nitriding
Authors: Guan Jing , Xiang Qing , Zhang Xiuhua , Liu Jing , Yang Feng
Published: February 2022

Nitride has high hardness and excellent wear resistance. It is frequently prepared on a material surface to improve material performance. The nitriding layer can be prepared in different ways, so the bonding strength and microstructure between the nitriding layer and the matrix differ, which will directly affect the surface mechanical properties of the material. In this study, pure titanium (TA1) was nitrided using electromagnetic induction nitriding, and the microstructure of nitriding layer was analysed using x-ray photoelectron spectroscopy (XPS), scanning electron microscopy-electron backscatter diffraction (SEM-EBSD) and scanning electron microscopy-energy-dispersive x-ray spectroscopy (SEM-EDS). In addition, the mechanical properties of the nitriding layer were studied using a nanoindentation and scratch tester. The experimental result shows a 20 μm induction nitriding layer composed of TiN, Ti2N and α(N)-Ti. The compound layer (Ti2N and TiN) was approximately 3 μm. The surface was contaminated with C and O elements, and evident segregation bands were found between the induction nitriding layer and matrix. The induction nitriding layer can considerably improve the wear resistance of titanium alloy, but the bonding force between the induction nitriding layer and matrix decreases owing to the segregation band.
Numerical study of the effect of coflow argon jet on a laminar argon thermal plasma jet
Authors: ZHOU Xu , CHEN Xianhui , YE Taohong , ZHU Minming , XIA Weidong
Published: February 2022

The effects of the velocity and width in coflow argon jet inlet on the flow characteristics of laminar argon thermal plasma jet flowing into the cold air have been studied by the large eddy simulation methods. The Kelvin–Helmholtz instability between argon thermal plasma jet and coflow argon jet causes the transition from a laminar jet to a turbulent jet in the presence of coflow argon jet. Moreover, increasing the velocity and width in coflow argon jet inlet can enhance turbulent transport and provoke coherent structure in the downstream of thermal plasma jet. And the mixing characteristics between argon thermal plasma, coflow argon and ambient air are strengthened. In addition, the width in coflow argon jet inlet has a significant effect on the distribution of temperature in the upstream of thermal plasma jet. It was also found that the transition occurs in advance with the increase of velocity and width in coflow argon jet inlet.
Contrasting impacts of net cloud radiative forcing on the surface temperature trends in India
Authors: Banerjee Ayan Kumar , Dutta Soumi , Dey Sagnik
Published: February 2022

The rise of spatial heterogeneity in surface temperature (T

s
) over India cannot be explained by only the direct effect of enhanced greenhouse gas forcing. Here we propose an analytical framework to estimate the impact of the net cloud radiative forcing (CRF) trend on the observed T

s
trend for the duration of 2000–2019. The cloud sensitivity (

λ

c
l
d

) estimated from the satellite observations vary in the range −0.180 to 0.241 K per W m−2 across the seven T

s
homogeneous zones in India. Net average (±1σ) CRFs over the Indian landmass during 2000–2019 in the shortwave and longwave are −15.5 ±11.3 and 12.4 ± 7.4 W m−2, −28.1 ± 22.4 and 24.6 ± 9.8 W m−2, −75.1 ± 20.4 and 55.0  ± 13.8 W m−2 and −23.3 ± 14.9 and 21.6 ± 14.8 W m−2, respectively for the winter (Dec-Feb), pre-monsoon (Mar–May), monsoon (Jun–Sep) and post-monsoon (Oct–Nov) seasons. We find that in some of the T

s
homogeneous regions, seasonal T

s
trends are suppressed, whereas in some other T

s
homogeneous regions, seasonal T

s
trends are accelerated by the net CRF. Our framework can be useful in studying the role of clouds in observed surface warming trends.
Microbiome Modelling Toolbox 2.0: efficient, tractable modelling of microbiome communities
Authors: Heinken Almut , Thiele Ines
Published: February 2022

Motivation

Constraint-Based Reconstruction and Analysis (COBRA) is a widely used approach for the interrogation and stratification of microbiome samples, yet applications to large-scale cohorts are hampered by limited scalability and efficiency of simulations.

Results

We substantially improved the computation speed and scalability of a previous implementation for the construction and interrogation of personalized constraint-based microbiome models as well as implemented additional functionalities for analysis and visualization.

Availability and implementation

Microbiome Modelling Toolbox and tutorials are freely available as part of the COBRA Toolbox at https://git.io/microbiomeModelingToolbox.
SIRT1 plays an important role in implantation and decidualization during mouse early pregnancy
Authors: Hwang Yeon Jeong , Sung Gi-Jun , Marquardt Ryan , Young Steven L , Lessey Bruce A , Kim Tae Hoon , Cheon Yong-Pil , Jeong Jae-Wook
Published: February 2022

Sirtuin 1 (SIRT1) is a member of the sirtuin family that functions to deacetylate both histones and non-histone proteins. Previous studies have identified significant SIRT1 upregulation in eutopic endometrium from infertile women with endometriosis. However, SIRT1 function in the uterus has not been directly studied. Using immunochemistry analysis, we found SIRT1 to be most strongly expressed at GD4.5 and GD5.5 in decidualized cells and at GD7.5 in secondary decidual cells in mouse. To assess the role of SIRT1 in uterine function, we generated uterine Sirt1 conditional knockout mice (Pgrcre/+Sirt1f/f; Sirt1d/d). A 6-month fertility trial revealed that Sirt1d/d females were subfertile. Implantation site numbers were significantly decreased in Sirt1d/d mice compared with controls at GD5.5. Sirt1d/d implantation sites at GD4.5 could be divided into two groups, Group #1 with luminal closure and nonspecific COX2 expression compared with controls (14/20) and Group #2 with an open lumen and no COX2 (6/20). In Sirt1d/d Group #1, nuclear FOXO1 expression in luminal epithelial cells was significantly decreased. In Sirt1d/d Group #2, nuclear FOXO1 expression was almost completely absent, and there was strong PGR expression in epithelial cells. At GD5.5, stromal PGR and COX2 were significantly decreased in Sirt1d/d uterine in the areas surrounding the embryo compared with controls, indicating defective decidualization. An artificially induced decidualization test revealed that Sirt1d/d females showed defects in decidualization response. All together, these data suggest that SIRT1 is important for decidualization and contributes to preparing a receptive endometrium for successful implantation.
Effects of progesterone and interferon tau on ovine endometrial phosphate, calcium, and vitamin D signaling
Authors: Stenhouse Claire , Halloran Katherine M , Moses Robyn M , Seo Heewon , Gaddy Dana , Johnson Gregory A , Wu Guoyao , Suva Larry J , Bazer Fuller W
Published: February 2022

Given recent reports of expression of postnatal mineral transport regulators at the maternal–conceptus interface during the peri-implantation period, this study tested the hypothesis that progesterone (P4) and interferon tau (IFNT) regulate phosphate, calcium, and vitamin D signaling in the ovine endometrium. Mature Rambouillet ewes (n = 24) were surgically fitted with intrauterine catheters on day 7 of the estrous cycle. Ewes received daily intramuscular injections of 50 mg of P4 in corn oil vehicle and 75 mg of progesterone receptor antagonist (RU486) in corn oil from days 8 to 15, and twice-daily intrauterine injections of either control proteins (CX) or IFNT (25 μg/uterine horn/day) from days 11 to 15 resulting in four treatment groups: P4 + CX; P4 + IFNT; RU486 + P4 + CX; and RU486 + P4 + IFNT. On day 16, ewes were hysterectomized. RU486 + P4 + CX treated ewes had lower concentrations of 25 (OH) D in plasma than P4 + CX treated ewes (P < 0.05). Endometria from ewes treated with IFNT had greater expression of FGF23 (P < 0.01), S100A9 (P < 0.05), and S100A12 (P = 0.05) mRNAs and lower expression of ADAM10 mRNA (P < 0.01) than of ewes treated with CX proteins. Expression of FGF23 mRNA was greater in endometria of ewes that received RU486 + P4 + IFNT than in ewes that received RU486 + P4 + CX (hormone × protein interaction, P < 0.05). The expression of S100G mRNA was greater in endometria of ewes that received P4 + IFNT compared to ewes that received RU486 + P4 + IFNT (P < 0.05; hormone × protein interaction, P < 0.01). These data implicate P4 and IFNT in the regulation of phosphate, calcium, and vitamin D signaling during the peri-implantation period of pregnancy and provide a platform for continued mechanistic investigations.
Chemokine C-X-C receptor 4 mediates recruitment of bone marrow-derived nonhematopoietic and immune cells to the pregnant uterus
Authors: Fang Yuan-Yuan , Lyu Fang , Abuwala Nafeesa , Tal Aya , Chen Alice Y , Taylor Hugh S , Tal Reshef
Published: February 2022

Bone marrow-derived progenitor cells (BMDPCs) are mobilized to the circulation in pregnancy and get recruited to the pregnant decidua where they contribute functionally to decidualization and successful implantation. However, the molecular mechanisms underlying BMDPCs recruitment to the decidua are unknown. CXCL12 ligand and its CXCR4 receptor play crucial roles in the mobilization and homing of stem/progenitor cells to various tissues. To investigate the role of CXCL12–CXCR4 axis in BMDPCs recruitment to decidua, we created transgenic GFP mice harboring CXCR4 gene susceptible to tamoxifen-inducible Cre-mediated ablation. These mice served as BM donors into wild-type C57BL/6 J female recipients using a 5-fluorouracil-based nongonadotoxic submyeloablation to achieve BM-specific CXCR4 knockout (CXCR4KO). Successful CXCR4 ablation was confirmed by RT-PCR and in vitro cell migration assays. Flow cytometry and immunohistochemistry showed a significant increase in GFP+ BM-derived cells (BMDCs) in the implantation site as compared to the nonpregnant uterus of control (2.7-fold) and CXCR4KO (1.8-fold) mice. This increase was uterus-specific and was not observed in other organs. This pregnancy-induced increase occurred in both hematopoietic (CD45+) and nonhematopoietic (CD45–) uterine BMDCs in control mice. In contrast, in CXCR4KO mice there was no increase in nonhematopoietic BMDCs in the pregnant uterus. Moreover, decidual recruitment of myeloid cells but not NK cells was diminished by BM CXCR4 deletion. Immunofluorescence showed the presence of nonhematopoietic GFP+ cells that were negative for CD45 (panleukocyte) and DBA (NK) markers in control but not CXCR4KO decidua. In conclusion, we report that CXCR4 expression in nonhematopoietic BMDPCs is essential for their recruitment to the pregnant decidua.
Prostaglandin E2 receptor 3 promotes M1 macrophages polarization in unexplained recurrent pregnancy loss
Authors: Ye Yao , Peng Lin , Chelariu-Raicu Anca , Kuhn Christina , Dong Xi , Jeschke Udo , von Schönfeldt Viktoria
Published: February 2022

Unexplained recurrent pregnancy loss (uRPL) is associated with macrophage polarization, which can be modulated by prostaglandin E2 (PGE2). Our previous study demonstrated that PGE2 receptor 3 (EP3) signaling is induced in the first-trimester placentas of uRPL patients compared with its expression in healthy controls. However, whether EP3 plays a role in macrophage polarization at the maternal-fetal interface of uRPL women remains unknown. The positive expression of EP3 in decidual macrophages was confirmed by double immunofluorescence staining in the first-trimester placentas collected from uRPL patients and healthy controls. Antibodies CD68, iNOS, and CD163 were used as immunofluorescence marker for decidual macrophages, M1, and M2 macrophages. To clarify the effects of EP3 on macrophage polarization, THP-1 monocyte cells were applied as M0 macrophages after phorbol 12-myristate 13-acetate (PMA) treatment for in vitro study. The mRNA levels of representative M1 markers (interleukin-1β and interleukin-6) and M2 markers (interleukin-10 and arginase-1) were quantified with qPCR in M0 macrophages being stimulated with sulprostone (an EP3 agonist) or L-798,106 (an EP3 antagonist). We found that EP3 expression was upregulated in the decidual macrophages of first-trimester placentas from uRPL patients compared with healthy controls. Furthermore, EP3 expression was increased in M1 macrophages compared with that in M2 macrophages in first-trimester placentas of uRPL patients. Sulprostone intensified the mRNA levels of IL-6 together with interferon-γ, whereas L-798,106 stimulated the mRNA expression of IL-10 and Arg-1 in a dose-dependent manner.
ActivatingRAC1variants in the switch II region cause a developmental syndrome and alter neuronal morphology
Authors: Banka Siddharth , Bennington Abigail , Baker Martin J , Rijckmans Ellen , Clemente Giuliana D , Ansor Nurhuda Mohamad , Sito Hilary , Prasad Pritha , Anyane-Yeboa Kwame , Badalato Lauren , Dimitrov Boyan , Fitzpatrick David , Hurst Anna C E , Jansen Anna C , Kelly Melissa A , Krantz Ian , Rieubland Claudine , Ross Meredith , Rudy Natasha L , Sanz Javier , Stouffs Katrien , Xu Zhuo Luan , Malliri Angeliki , Kazanietz Marcelo G , Millard Tom H
Published: February 2022

RAC1 is a highly conserved Rho GTPase critical for many cellular and developmental processes. De novo missense RAC1 variants cause a highly variable neurodevelopmental disorder. Some of these variants have previously been shown to have a dominant negative effect. Most previously reported patients with this disorder have either severe microcephaly or severe macrocephaly.

Here, we describe eight patients with pathogenic missense RAC1 variants affecting residues between Q61 and R68 within the switch II region of RAC1. These patients display variable combinations of developmental delay, intellectual disability, brain anomalies such as polymicrogyria and cardiovascular defects with normocephaly or relatively milder micro- or macrocephaly. Pulldown assays, NIH3T3 fibroblast spreading assays and staining for activated PAK1/2/3 and WAVE2 suggest that these variants increase RAC1 activity and over-activate downstream signalling targets. Axons of neurons isolated from Drosophila embryos expressing the most common of the activating variants are significantly shorter, with an increased density of filopodial protrusions. In vivo, these embryos exhibit frequent defects in axonal organization. Class IV dendritic arborization neurons expressing this variant exhibit a significant reduction in the total area of the dendritic arbour, increased branching and failure of self-avoidance. RNAi knock down of the WAVE regulatory complex component Cyfip significantly rescues these morphological defects.

These results establish that activating substitutions affecting residues Q61–R68 within the switch II region of RAC1 cause a developmental syndrome. Our findings reveal that these variants cause altered downstream signalling, resulting in abnormal neuronal morphology and reveal the WAVE regulatory complex/Arp2/3 pathway as a possible therapeutic target for activating RAC1 variants. These insights also have the potential to inform the mechanism and therapy for other disorders caused by variants in genes encoding other Rho GTPases, their regulators and downstream effectors.
Controversy over the temporal cortical terminations of the left arcuate fasciculus: a reappraisal
Authors: Giampiccolo Davide , Duffau Hugues
Published: February 2022

The arcuate fasciculus has been considered a major dorsal fronto-temporal white matter pathway linking frontal language production regions with auditory perception in the superior temporal gyrus, the so-called Wernicke’s area. In line with this tradition, both historical and contemporary models of language function have assigned primacy to superior temporal projections of the arcuate fasciculus. However, classical anatomical descriptions and emerging behavioural data are at odds with this assumption. On one hand, fronto-temporal projections to Wernicke’s area may not be unique to the arcuate fasciculus. On the other hand, dorsal stream language deficits have been reported also for damage to middle, inferior and basal temporal gyri that may be linked to arcuate disconnection. These findings point to a reappraisal of arcuate projections in the temporal lobe. Here, we review anatomical and functional evidence regarding the temporal cortical terminations of the left arcuate fasciculus by incorporating dissection and tractography findings with stimulation data using cortico–cortical evoked potentials and direct electrical stimulation mapping in awake patients. First, we discuss the fibres of the arcuate fasciculus projecting to the superior temporal gyrus and the functional rostro-caudal gradient in this region where both phonological encoding and auditory-motor transformation may be performed. Caudal regions within the temporoparietal junction may be involved in articulation and associated with temporoparietal projections of the third branch of the superior longitudinal fasciculus, while more rostral regions may support encoding of acoustic phonetic features, supported by arcuate fibres. We then move to examine clinical data showing that multimodal phonological encoding is facilitated by projections of the arcuate fasciculus to superior, but also middle, inferior and basal temporal regions. Hence, we discuss how projections of the arcuate fasciculus may contribute to acoustic (middle-posterior superior and middle temporal gyri), visual (posterior inferior temporal/fusiform gyri comprising the visual word form area) and lexical (anterior-middle inferior temporal/fusiform gyri in the basal temporal language area) information in the temporal lobe to be processed, encoded and translated into a dorsal phonological route to the frontal lobe. Finally, we point out surgical implications for this model in terms of the prediction and avoidance of neurological deficit.
Let’s talk about sex (in translational neuroscience)
Authors: Spires-Jones Tara L.
Published: February 2022

Our editor explores the importance of considering sex and gender in translational neuroscience.
SR-A neutralizing antibody: potential drug candidate for ameliorating osteoclastogenesis in rheumatoid arthritis
Authors: Xie Yang , Jiang Xiang , Wang Ping , Zheng Xi , Song Jing , Bai Mingxin , Tang Yundi , Fang Xiangyu , Jia Yuan , Li Zhanguo , Hu Fanlei
Published: February 2022

Rheumatoid arthritis (RA) is an autoimmune disease characterized by proliferative synovitis with deterioration of cartilage and bone. Osteoclasts (OCs) are the active participants in the bone destruction of RA. Although with great advances, most current therapeutic strategies for RA have limited effects on bone destruction. Macrophage scavenger receptor A (SR-A) is a class of pattern recognition receptors (PRRs) involved in bone metabolism and OC differentiation. More recently, our study revealed the critical role of SR-A in RA diagnosis and pathogenesis. Here, we further demonstrated that serum SR-A levels were positively correlated with bone destruction in patients with RA. Anti-SR-A neutralizing antibodies significantly inhibited OC differentiation and bone absorption in vitro in patients with RA, but not in healthy individuals, dampening the expression of OC-specific genes such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTSK), and matrix metalloproteinase-9 (MMP-9). Similar results were also seen in collagen-induced arthritis (CIA) mice in vitro. Moreover, the anti-SR-A neutralizing antibody could further ameliorate osteoclastogenesis in vivo and ex vivo in CIA mice, accompanied by decreased serum levels of C-terminal telopeptide and IL-6, exhibiting potential protective effects. These results suggest that blockade of SR-A using anti-SR-A neutralizing antibodies might provide a promising therapeutic strategy for bone destruction in the RA.
Differential expression of insulin-like growth factor type 1 receptor identifies heterogeneous intrahepatic regulatory T subsets in mouse hepatocellular carcinoma
Authors: Huang Yabing , Huang Ling , Zhu Jiling , Wu Yin , Shi Jinzhi , Dai Kai
Published: February 2022

Understanding regulatory T-cell (Treg)-mediated tumor tolerance is critical for designing immunotherapy against hepatocellular carcinoma (HCC). In this study, we characterized the expression of insulin-like growth factor type 1 receptor (IGF1R) in intrahepatic Tregs in a chemical-induced mouse HCC model. We found two intrahepatic Treg subsets with differential IGF1R expression: IGF1Rhi Tregs and IGF1Rlo/– Tregs. Functional assays indicated that compared with IGF1Rlo/– Tregs, IGF1Rhi Tregs produced more TGF-β and IL-10 and were more proliferative in vivo. Furthermore, IGF1Rhi Tregs exhibited higher phosphorylation of the mammalian target of the rapamycin complex 1 (mTORC1) in vivo. However, in vitro stimulation and immunosuppression assay revealed that the immunosuppressive capacity of the two Treg subsets was equivalent, as evidenced by comparable cytokine production and immunosuppressive effect over conventional T cells. The transcriptome sequencing analysis revealed up-regulation of genes that encode proteins essential for glycolysis, oxidative phosphorylation, and electron transport chain in IGF1Rhi Tregs. Consistently, IGF1Rhi Tregs produces more adenosine triphosphate (ATP), lactate, and reactive oxygen species (ROS). Furthermore, malignant cells in the tumor nodules induced IGF1R down-regulation in Tregs at the mRNA level. In summary, we identified the heterogeneity of intrahepatic Tregs in HCC which might play significant roles in tumor immunity.
Exposure of female NZBWF1 mice to imiquimod-induced lupus nephritis at an early age via a unique mechanism that differed from spontaneous onset
Authors: Hayakawa Kunihiro , Fujishiro Maki , Yoshida Yuko , Kataoka Yuko , Sakuma Shota , Nishi Takuya , Ikeda Keigo , Morimoto Shinji , Takamori Kenji , Sekigawa Iwao
Published: February 2022

Systemic lupus erythematosus (SLE) is a chronic inflammatory and representative autoimmune disease. Extremely complicated and multifactorial interactions between various genetic factors and individual susceptibility to environmental factors are involved in the pathogenesis of SLE. Several studies have reported that mutation and activation of toll-like receptor (TLR) 7 are involved in the onset of autoimmunity, including SLE. Thus, we investigated the response of SLE-prone mice to continuous environmental factors, particularly TLR7 agonist exposure, and changes in their phenotypes. Female and male NZBWF1 (BWF1) mice were treated from 20 weeks of age with a TLR7 agonist, imiquimod (IMQ), 3 times weekly for up to 12 weeks. IMQ-exposed female BWF1 mice showed worsened lupus nephritis. However, autoantibody production was not enhanced in IMQ-exposed female BWF1 mice. The Th1 cytokine expression was upregulated in the kidney of IMQ-treated mice. In IMQ-exposed BWF1 mice, neutralization of IFN-γ suppressed early-phase lupus nephritis. Additionally, in male BWF1 mice IMQ exposure induced minor aggravation of lupus nephritis. These results suggest that the induction of aggravated lupus nephritis by TLR7 agonist exposure was related to the expression of IFN-γ via acute TLR7 signal-induced renal inflammation, and that the involvement of genetic factors associated with a predisposition to SLE is also essential. Thus, the activation of TLR7 signaling by exposure to environmental factors may upset the balance of factors that maintain SLE remission. We hypothesize that the inhibition of TLR7 signaling and IFN-γ signaling is effective for preventing the onset and flare and maintaining remission of lupus nephritis.
Differentiation of circulating monocytes into macrophages with metabolically activated phenotype regulates inflammation in dyslipidemia patients
Authors: Berenice Martínez-Shio Elena , Martín Cárdenas-Hernández Ángel , Jiménez-Suárez Verónica , Sherell Marín-Jáuregui Laura , Castillo-Martin del Campo Claudia , González-Amaro Roberto , Escobedo-Uribe Carlos D , Monsiváis-Urenda Adriana Elizabeth
Published: February 2022

Macrophages are mediators of inflammation having an important role in the pathogenesis of cardiovascular diseases. Recently, a pro-inflammatory subpopulation, known as metabolically activated macrophages (MMe), has been described in conditions of obesity and metabolic syndrome where they are known to release cytokines that can promote insulin resistance. Dyslipidemia represents an important feature in metabolic syndrome and corresponds to one of the main modifiable risk factors for the development of cardiovascular diseases. Circulating monocytes can differentiate into macrophages under certain conditions. They correspond to a heterogeneous population, which include inflammatory and anti-inflammatory subsets; however, there is a wide spectrum of phenotypes. Therefore, we decided to investigate whether the metabolic activated monocyte (MoMe) subpopulation is already present under dyslipidemia conditions. Secondly, we assessed whether different levels of cholesterol and triglycerides play a role in the polarization towards the metabolic phenotype (MMe) of macrophages. Our results indicate that MoMe cells are found in both healthy and dyslipidemia patients, with cells displaying the following metabolic phenotype: CD14varCD36+ABCA1+PLIN2+. Furthermore, the percentages of CD14++CD68+CD80+ pro-inflammatory monocytes are higher in dyslipidemia than in healthy subjects. When analysing macrophage differentiation, we observed that MMe percentages were higher in the dyslipidemia group than in healthy subjects. These MMe have the ability to produce high levels of IL-6 and the anti-inflammatory cytokine IL-10. Furthermore, ABCA1 expression in MMe correlates with LDL serum levels. Our study highlights the dynamic contributions of metabolically activated macrophages in dyslipidemia, which may have a complex participation in low-grade inflammation due to their pro- and anti-inflammatory function.
The hyper-expression of NLRP4 characterizes the occurrence of macrophage activation syndrome assessing STING pathway in adult-onset Still’s disease
Authors: Ruscitti Piero , Berardicurti Onorina , Di Cola Ilenia , Di Muzio Claudia , Di Nino Elena , Giacomelli Roberto , Cipriani Paola
Published: February 2022

To assess stimulator of interferon genes (STING) pathway in patients with adult-onset Still’s disease (AOSD) who were complicated or not by macrophage activation syndrome (MAS), evaluating peripheral blood mononuclear cells (PBMCs), and synovial tissues. The relative mRNA expression of key molecules of the STING pathway (i.e. CGAS, NLRP4, PKDC, STING1, XRCC5, and XRCC6) and interferon (IFN)-γ was assessed in PBMCs obtained from patients with AOSD, who were complicated or not by MAS, and healthy controls (HCs). A bulky RNA sequencing was performed in synovial tissues from two patients with AOSD. Finally, the ability of heavy ferritin subunit (FeH) to induce the expression of NLRP4 was evaluated in cultured macrophages. Twenty patients with AOSD were analysed. Out of them, seven patients were complicated by MAS. Assessing mRNA relative expression in PBMCs, STING1, NLRP4, XRCC6, and IFN-γ were significantly expressed in AOSD than HCs. The mRNA relative expression of CGAS, PKDC, and XRCC5 did not differ between patients and HCs. Furthermore, NLRP4 and IFN-γ resulted to be significantly increased in patients with AOSD complicated by MAS than others. By RNA-sequencing analysis, we observed that Nlrp4 gene was significantly up-regulated in patients with AOSD. Following the stimulation with FeH, an increased expression of NLRP4 was observed in cultured macrophages. In conclusion, an increased expression of some key molecules of STING pathway characterized patients with AOSD. In addition, our results suggested that a hyper-activity of NLRP4 may be observed in patients with MAS. Furthermore, FeH increased the expression of NLRP4 in cultured macrophages.
Performance scaling for structural MRI surface parcellations: a machine learning analysis in the ABCD Study
Authors: Hahn Sage , Owens Max M , Yuan DeKang , Juliano Anthony C , Potter Alexandra , Garavan Hugh , Allgaier Nicholas
Published: February 2022

The use of predefined parcellations on surface-based representations of the brain as a method for data reduction is common across neuroimaging studies. In particular, prediction-based studies typically employ parcellation-driven summaries of brain measures as input to predictive algorithms, but the choice of parcellation and its influence on performance is often ignored. Here we employed preprocessed structural magnetic resonance imaging (sMRI) data from the Adolescent Brain Cognitive Development Study® to examine the relationship between 220 parcellations and out-of-sample predictive performance across 45 phenotypic measures in a large sample of 9- to 10-year-old children (N = 9,432). Choice of machine learning (ML) pipeline and use of alternative multiple parcellation-based strategies were also assessed. Relative parcellation performance was dependent on the spatial resolution of the parcellation, with larger number of parcels (up to ~4,000) outperforming coarser parcellations, according to a power–law scaling of between 1/4 and 1/3. Performance was further influenced by the type of parcellation, ML pipeline, and general strategy, with existing literature-based parcellations, a support vector-based pipeline, and ensembling across multiple parcellations, respectively, as the highest performing. These findings highlight the choice of parcellation as an important influence on downstream predictive performance, showing in some cases that switching to a higher resolution parcellation can yield a relatively large boost to performance.
The Executive-Led Planning Regime of the Hong Kong Special Administrative Region
Authors: Jhaveri Swati
Published: February 2022

This paper considers the distribution and accountability of planning powers in the urban planning regime of the Hong Kong SAR. This paper identifies the power holders who are charged with steering urban planning, with a view to demonstrating that despite the existence of a multi-actor and consultative process, there is a still a concentration of power on planning matters in particular organs of the executive branch of government. It is not unusual for planning powers to be concentrated in the executive branch of government: however, in the Hong Kong context it is the particular concentration of powers in a small circle of power holders within the executive branch that might need reform. The discussion concludes with sketching out possible ways of dispersing power, within and outside the executive branch, to enhance the legitimacy of the planning regime, without compromising its efficacy.
Lower marine productivity increases agonistic interactions between sea lions and fur seals in Northern Pacific Patagonia
Authors: Montalva Felipe , Pavés Hector , Pérez-Venegas Diego , Barrientos E Karin G , Valencia Carola , Miranda-Urbina Diego , Seguel Mauricio
Published: February 2022

Interspecific interactions are key drivers of individual and population-level fitness in a wide range of animals. However, in marine ecosystems, it is relatively unknown which biotic and abiotic factors impact behavioral interactions between competing species. We assessed the impact of weather, marine productivity, and population structure on the behavioral agonistic interactions between South American fur seals (SAFSs), Arctocephalus australis, and South American sea lions (SASLs), Otaria byronia, in a breeding colony of SAFS. We hypothesized that agonistic interactions between SAFSs and SASLs respond to biotic and abiotic factors such as SAFS population structure, marine productivity, and weather. We found that SASL and SAFS interactions almost always resulted in negative impacts on the social structure or reproductive success of the SAFS colony. SASL adult males initiated stampedes of SAFS and/or abducted and predated SAFS pups. Adult SAFS males abundance and severe weather events were negatively correlated with agonistic interactions between species. However, proxies for lower marine productivity such as higher sea surface temperature and lower catches of demerso-pelagic fish were the most important predictors of more frequent agonistic interactions between SAFS and SASL. Under the current scenario of decline in marine biomass due to global climate change and overfishing, agonistic interactions between competing marine predators could increase and exacerbate the negative impacts of environmental change in these species.
A Fiscal Constitutional Crisis: Tax Avoidance and Evasion in Inter-war Britain
Authors: Scott Peter
Published: February 2022

Inter-war Britain witnessed rising tax avoidance and evasion, reflecting a combination of elite opposition to higher tax rates and the almost complete absence of any effective legal or reputational sanctions against tax evaders. Legal tax avoidance carried little social stigma and even illegal evasion rarely led to criminal prosecution or public censure, on account of the confidential, non-judicial procedure by which cases were resolved. This paper explores how a combination of elite opposition to higher tax rates, a growing judicial ideology (especially in the higher courts) based around protecting ‘civil liberties’ (essentially construed in terms of private property rights), and an ambiguous stance on tax avoidance among policy-makers, created the conditions for the rapid growth of tax avoidance. This in turn fostered a booming tax avoidance industry that became a persistent feature of the British tax environment. The paper also explores the wider political economy of tax avoidance and evasion and how a political philosophy shared by leading judges, right-wing ‘anti-waste’ movements, some Conservative politicians, and many wealthy taxpayers, formed a precursor of neo-liberal political philosophy. Finally, it charts the changed tax climate of the late 1930s, when the growing threat of total war aligned the interests of the wealthy with those of the rest of society and allowed policy-makers to present tax payment as a patriotic duty. In this context, collective liberty and an ideology of ‘fair shares’ eclipsed the rhetoric of the rights of the propertied individual, thereby undermining the legitimacy of tax avoidance.
Screen capture technology in ELT
Authors: Stannard Russell
Published: February 2022

In this series, we explore technology-related themes and topics. The series aims to discuss and demystify what may be new areas for some readers and to consider their relevance for English language teachers.
Real-time inequality and the welfare state in motion: evidence from COVID-19 in Spain
Authors: Aspachs Oriol , Durante Ruben , Graziano Alberto , Mestres Josep , Montalvo Jose G , Reynal-Querol Marta
Published: February 2022

G. Montalvo and Marta Reynal-Querol?>Official statistics on economic inequality are only available at low frequency and with considerable delay. This makes it challenging to assess the impact on inequality of fast-unfolding crises like the COVID-19 pandemic, and to rapidly evaluate and tailor policy responses. We propose a new methodology to track income inequality at high frequency using anonymized data from bank records for over three million account holders in Spain. Using this approach, we analyse how inequality evolved between February and November 2020 (compared to the same months of 2019). We first show that the wage distribution in our data matches very closely that from official labour surveys. We then document that, in the absence of government intervention, inequality would have increased dramatically, mainly due to job losses and wage cuts experienced by low-wage workers. The increase in pre-transfer inequality was especially pronounced among the young and the foreign-born, and in regions more dependent on services. Public transfers and unemployment insurance schemes were effective at providing a safety net to the most affected segments of the population and at offsetting most of the increase in inequality. Increased inequality is primarily driven by differential changes in employment rate. Indeed, using individual-level regressions, we find that, over the course of the pandemic, the probability of being employed decreased drastically for workers in the lower part of the pre-COVID wage distribution, young cohorts and foreign-born.
Learning curve of visually-guided laser balloon ablation of paroxysmal atrial fibrillation
Authors: Kondo Y , Nakano M , Kajiyama T , Nakano M , Kobayashi Y
Published: February 2022

Funding Acknowledgements

Type of funding sources: None.

Background

The visually-guided laser balloon (VGLB) is a compliant, variable-diameter balloon that delivers laser energy around the pulmonary vein (PV) ostium under real-time endoscopic visualization. However, limited data exist in Japan thus far. Therefore, we determined the safety, efficacy, and learning curve of the VGLB for PV isolation.

Methods

A total of 52 consecutive patients with paroxysmal atrial fibrillation were prospectively enrolled and divided into 3 groups (T1 = 15 patients, T2 = 15 patients, T3 = 22 patients). All patients underwent PV isolation by 2 operators using the VGLB. The operators were experienced in radiofrequency and cryothermal procedures, but not in laser ablations.

Results

Tables show the acute clinical results. Reversible phrenic nerve palsy occurred in 3.8%, with a trend towards a lower complication rate with increasing experience.

Conclusions

The VGLB was safe and effective for PV isolation, even for operators without any previous experience. Procedure time decreased after a learning curve of 30 cases. Abstract Figure. Procedural data and isolation rates
Impact of preprocedural upper gastrointestinal endoscopy for pulmonary vein isolation - single-center experience of 400 patients
Authors: Grosse Meininghaus D , Kleemann T
Published: February 2022

Funding Acknowledgements

Type of funding sources: None.

Introduction

Mucosal esophageal lesions (ELs) are reported in 10-40% after pulmonary vein isolation (PVI) and may be precursors of (almost always lethal) atrio-esophageal fistula (AEF). Although mechanisms of lesion progression are not completely understood, inflammation (e.g. by acidic reflux) is thought to be a major contributor. However, ELs may also be preexisting or due to mechanical instrumentation rather than ablation-induced, and these lesions are not prone to progression. On the other hand, preexisting reflux-induced esophagitis might facilitate lesion generation during ablation.

Therefore, esophagogastroscopy (EGD) before PVI might reveal important information regarding preexisting vulnerability that needs to be considered/is relevant for ablation procedure planning.

Purpose

(1) To study the incidence of preexisting esophageal and upper gastrointestinal pathology detected by EGD in patients undergoing PVI. (2) To assess the impact of preprocedural EGD on procedure planning.

Methods

All consecutive patients undergoing PVI (radiofrequency energy PVI or cryoablation) had routine pre- and post-procedural EGD. The preexisting EGD-findings were analyzed with regard to their impact on PVI planning, postprocedural ELs, and additional endoscopic workup.

Results

From 08/2018 to 08/2021, 396 patients (66 ± 9 years, 58% male) were included. During preprocedural EGD, 207 patients (52%) had esophageal and extraesophageal abnormalities.

In 57 patients, the findings influenced the procedure strategy (e.g. in the presence of inflammation of the lower third of the esophagus, maximum power at the posterior left atrial wall was reduced from 25 to 20 Watts). 9/29 patients with new ELs in postprocedural EGD had preexisting esophagitis.

Ablation was postponed for five patients, thereof two with candida esophagitis, two with gastral and one with duodenal ulcer, respectively). 16 patients received further endoscopic workup with identification of a gastric carcinoma in one. Endoscopic ultrasound identified a patient with a pancreatic head neoplasia. There were no procedure-related complications of EGDs.

Discussion and Conclusion

In an unselected cohort, preprocedural EGD showed incidental findings in a half of the patients, and one-fourth of these were considered to be relevant for procedural aspects of PVI. Of particular interest is the absence of inflammation of the esophageal wall. Ulcer do not affect the safety of the PVI directly, but have impact on anticoagulation issues. EGD before PVI merits consideration. Abstract Figure. EGD-findings before PVI
Oral antithrombotic prescription patterns among hospitalized adult patients with non-valvular atrial fibrillation
Authors: Soco M L , Junia A T
Published: February 2022

Funding Acknowledgements

Type of funding sources: None.

Background

Oral anticoagulant (OAC) therapy reduces stroke risk in patients with atrial fibrillation. Despite extensive recommendations regarding the use of non-vitamin K antagonist oral anticoagulants (NOACs), available data shows that they remain underutilized. Additionally, data on OAC prescription patterns in relation to stroke and bleeding risk scores are scarce; more so in low to middle income countries. The aim of this study was to describe the antithrombotic prescription patterns among Filipino patients with non-valvular AF.

Methods

This retrospective, cross-sectional study included adult patients with non-valvular AF admitted from January to December 2019 in a single center. The antithrombotic therapy prescribed was reviewed for patterns according to the CHA2DS2-VASc and HAS-BLED risk scores. Creatinine clearance was also calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to determine the dose appropriateness of prescribed NOACs.

Results

We reviewed the records of 503 patients, and 302 were included in the study. Of these, 143 (47.35%), 61 (20.19%), 78 (25.83%) and 20 (6.62%) patients were on anticoagulant therapy alone, antiplatelet therapy alone, combination therapy, and no therapy, respectively. A total of 210 (69.54%) patients were prescribed with NOACs, of which 52.8% were dosed appropriately and 41.43% were underdosed. Among patients with high stroke risk but with low bleeding risk, only 39.63% were prescribed with an appropriately dosed NOAC. Thirty-three percent were given an underdosed NOAC while 16.28% received only antiplatelets and 4.65% received no antithrombotic therapy. Patients with low bleeding risk accounted for the majority of NOAC underdosage rates. Furthermore, 59 (20.48%) patients were prescribed with antiplatelets alone despite being stratified as having a high stroke risk. Warfarin use was also documented in 11 (3.64%) patients. Although accounting for only a minority, overdosed NOACs were observed among patients with high bleeding risk.

Conclusion

Over two-thirds of the patients with non-valvular AF were initiated on NOACs but only one-half received the appropriate dose. Rivaroxaban monotherapy or in combination with clopidogrel were the most frequently used agents. Antiplatelet therapy and underdosed NOACs constituted one-half of the antithrombotic therapy prescribed in high risk patients. The prescription patterns observed show that although the rate of NOAC use was high, a significant proportion of patients were still given suboptimal antithrombotic treatment. Abstract Figure. Baseline characteristics  Abstract Figure. Antothrombotic therapy