bluuebunny/crossref_metadata_2025 huggingface dataset:
Mercury accumulation in vegetable Houttuynia cordata Thunb. from two different geological areas in southwest China and implications for human consumption
Authors: Wang Qingfeng , Li Zhonggen , Feng Xinbin , Wang Ao , Li Xinyu , Wang Dan , Fan Leilei
Published: January 2021

Houttuynia cordata Thunb. (HCT) is a common vegetable native to southwest China, and grown for consumption. The results suggested that THg contents in all parts and MeHg in underground parts of HCT in Hg mining areas were much higher than those in non-Hg mining areas. The highest THg and MeHg content of HCT were found in the roots, followed by the other tissues in the sequence: roots > leaves > rhizomes > aboveground stems (THg), and roots > rhizomes > aboveground stems > leaves (MeHg). The average THg bioaccumulation factor (BCF) of HCT root in the Hg mining area and in non-Hg mining areas could reach 1.02 ± 0.71 and 0.99 ± 0.71 respectively, indicating that HCT is a Hg accumulator. And the THg and MeHg contents in all tissues of HCT, including the leaves, were significantly correlated with THg and MeHg content in the soil. Additionally, preferred dietary habits of HCT consumption could directly affect the Hg exposure risk. Consuming the aboveground parts (CAP) of HCT potentially poses a high THg exposure risk and consuming the underground parts (CUP) may lead to a relatively high MeHg exposure risk. Only consuming the rhizomes (OCR) of the underground parts could significantly reduce the exposure risk of THg and to some extent of MeHg. In summary, HCT should not be cultivated near the Hg contaminated sites, such as Hg tailings, as it is associated with a greater risk of Hg exposure and high root Hg levels, and the roots should be removed before consumption to reduce the Hg risk.
miR299a-5p promotes renal fibrosis by suppressing the antifibrotic actions of follistatin
Authors: Mehta Neel , Li Renzhong , Zhang Dan , Soomro Asfia , He Juehua , Zhang Ivan , MacDonald Melissa , Gao Bo , Krepinsky Joan C.
Published: January 2021

Caveolin-1 (cav-1), an integral protein of the membrane microdomains caveolae, is required for synthesis of matrix proteins by glomerular mesangial cells (MC). Previously, we demonstrated that the antifibrotic protein follistatin (FST) is transcriptionally upregulated in cav-1 knockout MC and that its administration is protective against renal fibrosis. Here, we screened cav-1 wild-type and knockout MC for FST-targeting microRNAs in order to identity novel antifibrotic therapeutic targets. We identified that miR299a-5p was significantly suppressed in cav-1 knockout MC, and this was associated with stabilization of the FST 3′UTR. Overexpression and inhibition studies confirmed the role of miR299a-5p in regulating FST expression. Furthermore, the profibrotic cytokine TGFβ1 was found to stimulate the expression of miR299a-5p and, in turn, downregulate FST. Through inhibition of FST, miR299a-5p overexpression augmented, while miR299a-5p inhibition diminished TGFβ1 profibrotic responses, whereas miR299a-5p overexpression re-enabled cav-1 knockout MC to respond to TGFβ1. In vivo, miR299a-5p was upregulated in the kidneys of mice with chronic kidney disease (CKD). miR299a-5p inhibition protected these mice against renal fibrosis and CKD severity. Our data demonstrate that miR299a-5p is an important post-transcriptional regulator of FST, with its upregulation an important pathogenic contributor to renal fibrosis. Thus, miR299a-5p inhibition offers a potential novel therapeutic approach for CKD.
Stimulus-evoked phase-locked activity along the human auditory pathway strongly varies across individuals
Authors: Gransier Robin , Hofmann Michael , van Wieringen Astrid , Wouters Jan
Published: January 2021

Phase-locking to the temporal envelope of speech is associated with envelope processing and speech perception. The phase-locked activity of the auditory pathway, across modulation frequencies, is generally assessed at group level and shows a decrease in response magnitude with increasing modulation frequency. With the exception of increased activity around 40 and 80 to 100 Hz. Furthermore, little is known about the phase-locked response patterns to modulation frequencies ≤ 20 Hz, which are modulations predominately present in the speech envelope. In the present study we assess the temporal modulation transfer function (TMTFASSR) of the phase-locked activity of the auditory pathway, from 0.5 to 100 Hz at a high-resolution and by means of auditory steady-state responses. Although the group-averaged TMTFASSR corresponds well with those reported in the literature, the individual TMTFASSR shows a remarkable intersubject variability. This intersubject variability is especially present for ASSRs that originate from the cortex and are evoked with modulation frequencies ≤ 20 Hz. Moreover, we found that these cortical phase-locked activity patterns are robust over time. These results show the importance of the individual TMTFASSR when assessing phase-locked activity to envelope fluctuations, which can potentially be used as a marker for auditory processing.
A novel immune prognostic index for stratification of high-risk patients with early breast cancer
Authors: Lee Hannah , Kwon Mi Jeong , Koo Beom-Mo , Park Hee Geon , Han Jinil , Shin Young Kee
Published: January 2021

The prognostic value of current multigene assays for breast cancer is limited to hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer. Despite the prognostic significance of immune response-related genes in breast cancer, immune gene signatures have not been incorporated into most multigene assays. Here, using public gene expression microarray datasets, we classified breast cancer patients into three risk groups according to clinical risk and proliferation risk. We then developed the immune prognostic index based on expression of five immune response-related genes (TRAT1, IL2RB, CTLA4, IGHM and IL21R) and lymph node status to predict the risk of recurrence in the clinical and proliferation high-risk (CPH) group. The 10-year probability of disease-free survival (DFS) or distant metastasis-free survival (DMFS) of patients classified as high risk according to the immune prognostic index was significantly lower than those of patients classified as intermediate or low risk. Multivariate analysis revealed that the index is an independent prognostic factor for DFS or DMFS. Moreover, the C-index revealed that it is superior to clinicopathological variables for predicting prognosis. Its prognostic significance was also validated in independent datasets. The immune prognostic index identified low-risk patients among patients classified as CPH, regardless of the molecular subtype of breast cancer, and may overcome the limitations of current multigene assays.
Effect of ball collision direction on a wet mechanochemical reaction
Authors: Kozawa Takahiro , Fukuyama Kayo , Kushimoto Kizuku , Ishihara Shingo , Kano Junya , Kondo Akira , Naito Makio
Published: January 2021

Mechanochemical reactions can be induced in a solution by the collision of balls to produce high-temperature and high-pressure zones, with the reactions occurring through a dissolution–precipitation mechanism due to a change in solubility. However, only a fraction of the impact energy contributes to the mechanochemical reactions, while the rest is mainly consumed by the wear of balls and the heat generation. To clarify whether the normal or tangential component of collisions makes a larger contribution on the reaction, herein we studied the effect of collision direction on a wet mechanochemical reaction through combined analysis of the experimental reaction rates and simulated ball motion. Collisions of balls in the normal direction were found to contribute strongly to the wet mechanochemical reaction. These results could be used to improve the synthesis efficiency, predict the reaction, and lower the wear in the wet mechanochemical reactions.
Urban life promotes delayed dispersal and family living in a non-social bird species
Authors: Luna Álvaro , Lois Nicolás A. , Rodríguez-Martinez Sol , Palma Antonio , Sanz-Aguilar Ana , Tella José L. , Carrete Martina
Published: January 2021

In some vertebrate species, family units are typically formed when sexually mature individuals delay dispersal and independent breeding to remain as subordinates in a breeding group. This behaviour has been intensively studied in gregarious species but has also been described in non-social species where ecological and evolutionary drivers are less known. Here, we explore factors that favour delayed dispersal and family living and potential benefits associated with this strategy in a non-social, monogamous species (the burrowing owl,Athene cunicularia) occupying urban and rural habitats. Our results show that family units arise when first-year individuals, mainly males, delay their dispersal to stay in their natal nests with their parents. This delayed dispersal, while still uncommon, was more prevalent in urban (7%) than in rural (3%) habitats, and in areas with high conspecific density and productivity. Birds delaying dispersal contributed to the genetic pool of the offspring in 25% of the families analysed, but did not increase the productivity of the nests where they remained. However, their presence was related to an improvement in the body condition of chicks, which was ultimately linked to a slightly positive effect in offspring future survival probabilities. Finally, delayed dispersers were recruited as breeders in high-quality urban territories and closer to their natal nests than individuals dispersing during their first year of life. Thus, our results suggest that delaying dispersal may be mainly related to opportunities to inheriting a good quality territory, especially for males. Our study contributes to understanding the role played by habitat quality in promoting delayed dispersal and family living, not only in social but also non-social species, highlighting its impact in the ecology and evolution of animal populations.
Assessing ZNF154 methylation in patient plasma as a multicancer marker in liquid biopsies from colon, liver, ovarian and pancreatic cancer patients
Authors: Miller Brendan F. , Petrykowska Hanna M. , Elnitski Laura
Published: January 2021

One epigenetic hallmark of many cancer types is differential DNA methylation occurring at multiple loci compared to normal tissue. Detection and assessment of the methylation state at a specific locus could be an effective cancer diagnostic. We assessed the effectiveness of hypermethylation at the CpG island of ZNF154, a previously reported multi-cancer specific signature for use in a blood-based cancer detection assay. To predict its effectiveness, we compared methylation levels of 3698 primary tumors encompassing 11 solid cancers, 724 controls, 2711 peripheral blood cell samples, and 350 noncancer disease tissues from publicly available methylation array datasets. We performed a single-molecule high-resolution DNA melt analysis on 71 plasma samples from cancer patients and 20 noncancer individuals to assess ZNF154 methylation as a candidate diagnostic metric in liquid biopsy and compared results to KRAS mutation frequency in the case of pancreatic carcinoma. We documented ZNF154 hypermethylation in early stage tumors, which did not increase in most noncancer disease or with respect to age or sex in peripheral blood cells, suggesting it is a promising target in liquid biopsy. ZNF154 cfDNA methylation discriminated cases from healthy donor plasma samples in minimal plasma volumes and outperformed KRAS mutation frequency in pancreatic cancer.
A novel simple risk model to predict the prognosis of patients with paraquat poisoning
Authors: Gao Yanxia , Liu Liwen , Li Tiegang , Yuan Ding , Wang Yibo , Xu Zhigao , Hou Linlin , Zhang Yan , Duan Guoyu , Sun Changhua , Che Lu , Li Sujuan , Sun Pei , Li Yi , Ren Zhigang
Published: January 2021

To identify risk factors and develop a simple model to predict early prognosis of acute paraquat (PQ) poisoning patients, we performed a retrospective cohort study of acute PQ poisoning patients (n = 1199). Patients (n = 913) with PQ poisoning from 2011 to 2018 were randomly divided into training (n = 609) and test (n = 304) samples. Another two independent cohorts were used as validation samples for a different time (n = 207) and site (n = 79). Risk factors were identified using a logistic model with Markov Chain Monte Carlo (MCMC) simulation and further evaluated using a latent class analysis. The prediction score was developed based on the training sample and was evaluated using the testing and validation samples. Eight factors, including age, ingestion volume, creatine kinase-MB [CK-MB], platelet [PLT], white blood cell [WBC], neutrophil counts [N], gamma-glutamyl transferase [GGT], and serum creatinine [Cr] were identified as independent risk indicators of in-hospital death events. The risk model had C statistics of 0.895 (95% CI 0.855–0.928), 0.891 (95% CI 0.848–0.932), and 0.829 (95% CI 0.455–1.000), and predictive ranges of 4.6–98.2%, 2.3–94.9%, and 0–12.5% for the test, validation_time, and validation_site samples, respectively. In the training sample, the risk model classified 18.4%, 59.9%, and 21.7% of patients into the high-, average-, and low-risk groups, with corresponding probabilities of 0.985, 0.365, and 0.03 for in-hospital death events. We developed and evaluated a simple risk model to predict the prognosis of patients with acute PQ poisoning. This risk scoring system could be helpful for identifying high-risk patients and reducing mortality due to PQ poisoning.
Soil gross nitrogen transformations in forestland and cropland of Regosols
Authors: Ren Xiao , Zhang Jinbo , Bah Hamidou , Müller Christoph , Cai Zucong , Zhu Bo
Published: January 2021

Soil gross nitrogen (N) transformations could be influenced by land use change, however, the differences in inherent N transformations between different land use soils are still not well understood under subtropical conditions. In this study, an 15N tracing experiment was applied to determine the influence of land uses on gross N transformations in Regosols, widely distributed soils in Southwest China. Soil samples were taken from the dominant land use types of forestland and cropland. In the cropland soils, the gross autotrophic nitrification rates (mean 14.54 ± 1.66 mg N kg−1 day−1) were significantly higher, while the gross NH4+ immobilization rates (mean 0.34 ± 0.10 mg N kg−1 day−1) were significantly lower than those in the forestland soils (mean 1.99 ± 0.56 and 6.67 ± 0.74 mg N kg−1 day−1, respectively). The gross NO3− immobilization and dissimilatory NO3− reduction to NH4+ (DNRA) rates were not significantly different between the forestland and cropland soils. In comparison to the forestland soils (mean 0.51 ± 0.24), the cropland soils had significantly lower NO3− retention capacities (mean 0.01 ± 0.01), indicating that the potential N losses in the cropland soils were higher. The correlation analysis demonstrated that soil gross autotrophic nitrification rate was negatively and gross NH4+ immobilization rate was positively related to the SOC content and C/N ratio. Therefore, effective measures should be taken to increase soil SOC content and C/N ratio to enhance soil N immobilization ability and NO3− retention capacity and thus reduce NO3− losses from the Regosols.
Distribution, toxicity load, and risk assessment of dissolved metal in surface and overlying water at the Xiangjiang River in southern China
Authors: Huang Zhifeng , Zheng Saisai , Liu Yan , Zhao Xingru , Qiao Xiaocui , Liu Chengyou , Zheng Binghui , Yin Daqiang
Published: January 2021

Metal pollution in drinking water source has been under scrutiny as it seriously affects human health. This work examined 12 dissolved metals in the surface and overlying water of the Xiangjiang River, an important drinking water source in southern China, and characterized their distribution, identified their possible sources, assessed their toxicity load, and determined their potential ecological and health risk. No significant difference was found in the metal concentration between surface and overlying water. The average metal concentration fell in the order of Mg > Mn > Ba > Fe > Zn > As > Sb > Ni > Cd > V > Cr > Co, and all was lower than the safety threshold in the drinking water guideline of China. Anthropogenic activities were found to be the main source of metals from correlation analysis, principal component analysis (PCA), and cluster analysis (CA). According to the total heavy metal toxicity load (HMTL), 98.20%, 71.54%, 68.88%, and 7.97% of As, Cd, Sb, and Mn should be removed from the surface water to ensure safety. Most water samples from the surveyed area were found to have high ecological risk as was measured by the ecological risk index (RI). Health risk assessment showed that children are more susceptible than adults to the non-carcinogenic risk of dissolved metals, and the potential carcinogenic risk (CR) of As and Cd should be addressed. The results provide guidance for controlling the metal pollution of the Xiangjiang River and improving its quality as a drinking water source.
Unveiling the neuromechanical mechanisms underlying the synergistic interactions in human sensorimotor system
Authors: Honarvar S. , Kim C. , Diaz-Mercado Y. , Koh K. , Kwon H. J. , Kiemel T. , Caminita M. , Hahn J. O. , Shim J. K.
Published: January 2021

Motor synergies are neural organizations of a set of redundant motor effectors that interact with one another to compensate for each other’s error and ensure the stabilization of a performance variable. Recent studies have demonstrated that central nervous system synergistically coordinates its numerous motor effectors through Bayesian multi-sensory integration. Deficiency in sensory synergy weakens the synergistic interaction between the motor effectors. Here, we scrutinize the neuromechanical mechanism underlying this phenomenon through spectral analysis and modeling. We validate our model-generated results using experimental data reported in the literature collected from participants performing a finger force production task with and without tactile feedback (manipulated through injection of anesthetic in fingers). Spectral analysis reveals that the error compensation feature of synergies occurs only at low frequencies. Modeling suggests that the neurophysiological structures involving short-latency back-coupling loops similar to the well-known Renshaw cells explain the deterioration of synergy due to sensory deprivation.
DNA sequences performs as natural language processing by exploiting deep learning algorithm for the identification of N4-methylcytosine
Authors: Wahab Abdul , Tayara Hilal , Xuan Zhenyu , Chong Kil To
Published: January 2021

N4-methylcytosine is a biochemical alteration of DNA that affects the genetic operations without modifying the DNA nucleotides such as gene expression, genomic imprinting, chromosome stability, and the development of the cell. In the proposed work, a computational model, 4mCNLP-Deep, used the word embedding approach as a vector formulation by exploiting deep learning based CNN algorithm to predict 4mC and non-4mC sites on theC.elegansgenome dataset. Diversity of ranges employed for the experimental such as corpus k-mer and k-fold cross-validation to obtain the prevailing capabilities. The 4mCNLP-Deep outperform from the state-of-the-art predictor by achieving the results in five evaluation metrics by following; Accuracy (ACC) as 0.9354, Mathew’s correlation coefficient (MCC) as 0.8608, Specificity (Sp) as 0.89.96, Sensitivity (Sn) as 0.9563, and Area under curve (AUC) as 0.9731 by using 3-mer corpus word2vec and 3-fold cross-validation and attained the increment of 1.1%, 0.6%, 0.58%, 0.77%, and 4.89%, respectively. At last, we developed the online webserverhttp://nsclbio.jbnu.ac.kr/tools/4mCNLP-Deep/, for the experimental researchers to get the results easily.
A bi-specific lectin from the mushroom Boletopsis grisea and its application in glycoanalytical workflows
Authors: Ganatra Mehul B. , Potapov Vladimir , Vainauskas Saulius , Francis Anthony Z. , McClung Colleen M. , Ruse Cristian I. , Ong Jennifer L. , Taron Christopher H.
Published: January 2021

The BLL lectin from the edible Japanese “Kurokawa” mushroom (Boletopsis leucomelaena) was previously reported to bind to N-glycans harboring terminal N-acetylglucosamine (GlcNAc) and to induce apoptosis in a leukemia cell line. However, its gene has not been reported. In this study, we used a transcriptomics-based workflow to identify a full-length transcript of a BLL functional ortholog (termed BGL) from Boletopsis grisea, a close North American relative of B. leucomelaena. The deduced amino acid sequence of BGL was an obvious member of fungal fruit body lectin family (Pfam PF07367), a highly conserved group of mushroom lectins with a preference for binding O-glycans harboring the Thomsen–Friedenreich antigen (TF-antigen; Galβ1,3GalNAc-α-) and having two ligand binding sites. Functional characterization of recombinant BGL using glycan microarray analysis and surface plasmon resonance confirmed its ability to bind both the TF-antigen and β-GlcNAc-terminated N-glycans. Structure-guided mutagenesis of BGL’s two ligand binding clefts showed that one site is responsible for binding TF-antigen structures associated with O-glycans, whereas the second site specifically recognizes N-glycans with terminal β-GlcNAc. Additionally, the two sites show no evidence of allosteric communication. Finally, mutant BGL proteins having single functional bindings site were used to enrich GlcNAc-capped N-glycans or mucin type O-glycopeptides from complex samples in glycomics and glycoproteomics analytical workflows.
Factors associated with left ventricular reverse remodelling after percutaneous coronary intervention in patients with left ventricular systolic dysfunction
Authors: Adachi Yusuke , Kiyosue Arihiro , Ando Jiro , Kawahara Takuya , Kodera Satoshi , Minatsuki Shun , Kikuchi Hironobu , Inaba Toshiro , Kiriyama Hiroyuki , Hirose Kazutoshi , Shinohara Hiroki , Saito Akihito , Fujiwara Takayuki , Hara Hironori , Ueda Kazutaka , Sakakura Kenichi , Hatano Masaru , Harada Mutsuo , Takimoto Eiki , Akazawa Hiroshi , Morita Hiroyuki , Momomura Shin-ichi , Fujita Hideo , Komuro Issei
Published: January 2021

Percutaneous coronary intervention (PCI) is sometimes considered as an alternative therapeutic strategy to surgical revascularization in patients with coronary artery disease (CAD) and reduced left ventricular ejection fraction (LVEF). However, the types or conditions of patients that receive the clinical benefit of left ventricular reverse remodelling (LVRR) remain unknown. The purpose of this study was to investigate the determinants of LVRR following PCI in CAD patients with reduced LVEF. From 4394 consecutive patients who underwent PCI, a total of 286 patients with reduced LV systolic function (LVEF < 50% at initial left ventriculography) were included in the analysis. LVRR was defined as LV end-systolic volume reduction ≥ 15% and improvement of LVEF ≥ 10% at 6 months follow-up left ventriculography. Patients were divided into LVRR (n = 63) and non-LVRR (n = 223) groups. Multivariate logistic regression analysis revealed that unprotected left main coronary artery (LMCA) intervention was significantly associated with LVRR (P = 0.007, odds ratios [OR] 4.70, 95% confidence interval [CI] 1.54–14.38), while prior PCI (P = 0.001, OR 0.35, 95% CI 0.19–0.66), presence of in-stent restenosis (P = 0.016, OR 0.32, 95% CI 0.12–0.81), and presence of de-novo stenosis (P = 0.038, OR 0.36, 95% CI 0.14–0.95) were negatively associated with LVRR. These data suggest the potential prognostic benefit of unprotected LMCA intervention for LVRR and importance of angiographic follow-up in patients with CAD and LV systolic dysfunction.
Early age at menarche and metabolic cardiovascular risk factors: mediation by body composition in adulthood
Authors: Bubach Susana , Horta Bernardo Lessa , Gonçalves Helen , Assunção Maria Cecília Formoso
Published: January 2021

Evidence suggests that early menarche increases cardiometabolic risk, and adiposity would be a possible mediator of this association. We assessed the association between age at menarche and metabolic cardiovascular risk factors and estimated the indirect effect of body composition in adulthood. In 1982, all hospital births in the city of Pelotas/Brazil, were identified and live births were examined and have been prospectively followed. At 30 years, information on age at menarche and metabolic cardiovascular risk factors was available for 1680 women. Mediation analysis was performed using G-computation to estimate the direct effect of age at menarche and the indirect effect of body composition. The prevalence of age at menarche < 12 years was 24.5% and was associated with higher mean diastolic blood pressure [β: 1.98; 95% CI: 0.56, 3.40], total cholesterol (β: 8.28; 95% CI: 2.67, 13.88), LDL-cholesterol (β: 6.53; 95% CI: 2.00, 11.07), triglycerides (β: 0.11; 95% CI: 0.03, 0.19). For diastolic blood pressure, total cholesterol, LDL-cholesterol, triglycerides, body composition assessed by fat mass index captured from 43.8 to 98.9% of the effect of early menarche, except to systolic blood pressure, HDL-cholesterol, C-reactive-protein. Suggesting that the effect of menarche age < 12 years on some metabolic cardiovascular risk factors is mediated partially by body composition in adulthood.
Bioavailable fluoride in calcium-containing dentifrices
Authors: Shen Peiyan , Fernando James R. , Yuan Yi , Walker Glenn D. , Reynolds Coralie , Reynolds Eric C.
Published: January 2021

Calcium added to dentifrices can complex with fluoride ions to reduce intra-oral bioavailability and therefore efficacy in preventing dental caries. Six commercially available dentifrices containing different types of calcium and fluoride were analyzed for total and bioavailable fluoride levels by adding 10 g of dentifrice to 30 mL of distilled deionized water and mixing vigorously for 1 min to simulate toothbrushing. One milliliter of the dentifrice/water slurry was immediately centrifuged and the supernatant removed for bioavailable fluoride analysis and the mixed slurry prior to centrifugation used for total fluoride analysis using a modified microdiffusion method. The concentration of fluoride was determined using a fluoride ion-selective electrode calibrated with internal fluoride standards. All the dentifrices had similar total fluoride concentrations to those indicated on their labels (94% to 105%). However, only one dentifrice that contained calcium in the form of casein phosphopeptide amorphous calcium phosphate (CPP-ACP) had almost 100% (97%) of fluoride in bioavailable form. The other dentifrices contained calcium carbonate and they exhibited significantly (p < 0.001) lower bioavailable fluoride levels (27% to 61%), through the generation of poorly soluble fluoride phases. The saliva biomimetic CPP, as CPP-ACP, in a dentifrice stabilised calcium and fluoride ions to maintain fluoride’s bioavailability.
Nuclear IL-33 restrains the early conversion of fibroblasts to an extracellular matrix-secreting phenotype
Authors: Gatti Francesca , Mia Sobuj , Hammarström Clara , Frerker Nadine , Fosby Bjarte , Wang Junbai , Pietka Wojciech , Sundnes Olav , Hol Johanna , Kasprzycka Monika , Haraldsen Guttorm
Published: January 2021

Interleukin (IL)-33 is a cytokine that appears to mediate fibrosis by signaling via its receptor ST2 (IL-33R/IL1RL1). It is also, however, a protein that after synthesis is sorted to the cell nucleus, where it appears to affect chromatin folding. Here we describe a novel role for nuclear IL-33 in regulating the fibroblast phenotype in murine kidney fibrosis driven by unilateral ureteral obstruction. Transcriptional profiling of IL-33-deficient kidneys 24 h after ligation revealed enhanced expression of fibrogenic genes and enrichment of gene sets involved in extracellular matrix formation and remodeling. These changes relied on intracellular effects of IL-33, because they were not reproduced by treatment with a neutralizing antibody to IL-33 that prevents IL-33R/ST2L receptor signaling nor were they observed in IL-33R/ST2-deficient kidneys. To further explore the intracellular function of IL-33, we established transcription profiles of human fibroblasts, observing that knockdown of IL-33 skewed the transcription profile from an inflammatory towards a myofibroblast phenotype, reflected in higher levels of COL3A1, COL5A1 and transgelin protein, as well as lower expression levels of IL6, CXCL8, CLL7 and CCL8. In conclusion, our findings suggest that nuclear IL-33 in fibroblasts dampens the initial profibrotic response until persistent stimuli, as enforced by UUO, can override this protective mechanism.
Effects of different vibration frequencies on muscle strength, bone turnover and walking endurance in chronic stroke
Authors: Yang Zhenhui , Miller Tiev , Xiang Zou , Pang Marco Y. C.
Published: January 2021

This randomized controlled trial aimed to evaluate the effects of different whole body vibration (WBV) frequencies on concentric and eccentric leg muscle strength, bone turnover and walking endurance after stroke. The study involved eighty-four individuals with chronic stroke (mean age = 59.7 years, SD = 6.5) with mild to moderate motor impairment (Fugl-Meyer Assessment lower limb motor score: mean = 24.0, SD = 3.5) randomly assigned to either a 20 Hz or 30 Hz WBV intervention program. Both programs involved 3 training sessions per week for 8 weeks. Isokinetic knee concentric and eccentric extension strength, serum level of cross-linked N-telopeptides of type I collagen (NTx), and walking endurance (6-min walk test; 6MWT) were assessed at baseline and post-intervention. An intention-to-treat analysis revealed a significant time effect for all muscle strength outcomes and NTx, but not for 6MWT. The time-by-group interaction was only significant for the paretic eccentric knee extensor work, with a medium effect size (0.44; 95% CI: 0.01, 0.87). Both WBV protocols were effective in improving leg muscle strength and reducing bone resorption. Comparatively greater improvement in paretic eccentric leg strength was observed for the 30 Hz protocol.
Geological and Pleistocene glaciations explain the demography and disjunct distribution of red panda (A. fulgens) in eastern Himalayas
Authors: Dalui Supriyo , Singh Sujeet Kumar , Joshi Bheem Dutt , Ghosh Avijit , Basu Shambadeb , Khatri Hiren , Sharma Lalit Kumar , Chandra Kailash , Thakur Mukesh
Published: January 2021

Pleistocene glaciations facilitated climatic oscillations that caused for enormous heterogeneity in landscapes, and consequently affected demography and distribution patterns of the mountain endemic species. In this context, we investigated demographic history and population genetic structure of red panda, distributed along the geographical proximity in the southern edge of the Qinghai-Tibetan Plateau. Bayesian based phylogeny demonstrated that red panda diverged about 0.30 million years ago (CI 0.23–0.39) into two phylogenetic (sub) species, that correspond to the middle-late Pleistocene transition. The observed intraspecific clades with respect to Himalayan and Chinese red panda indicated restricted gene flow resulting from the Pleistocene glaciations in the eastern and southern Tibetan Plateau. We found Himalayan red panda population at least in KL-India declined abruptly in last 5–10 thousand years after being under demographic equilibrium. We suggest revisiting the ongoing conservation activities through cross border collaboration by developing multi-nationals, and multi-lateral species-oriented conservation action plans to support the red panda populations in transboundary landscapes.
The negative elongation factor NELF promotes induced transcriptional response of Drosophila ecdysone-dependent genes
Authors: Mazina Marina Yu. , Kovalenko Elena V. , Vorobyeva Nadezhda E.
Published: January 2021

For many years it was believed that promoter-proximal RNA-polymerase II (Pol II) pausing manages the transcription of genes inDrosophiladevelopment by controlling spatiotemporal properties of their activation and repression. But the exact proteins that cooperate to stall Pol II in promoter-proximal regions of developmental genes are still largely unknown. The current work describes the molecular mechanism employed by the Negative ELongation Factor (NELF) to control the Pol II pause at genes whose transcription is induced by 20-hydroxyecdysone (20E). According to our data, the NELF complex is recruited to the promoters and enhancers of 20E-dependent genes. Its presence at the regulatory sites of 20E-dependent genes correlates with observed interaction between the NELF-A subunit and the ecdysone receptor (EcR). The complete NELF complex is formed at the 20E-dependent promoters and participates in both their induced transcriptional response and maintenance of the uninduced state to keep them ready for the forthcoming transcription. NELF depletion causes a significant decrease in transcription induced by 20E, which is associated with the disruption of Pol II elongation complexes. A considerable reduction in the promoter-bound level of the Spt5 subunit of transcription elongation factor DSIF was observed at the 20E-dependent genes upon NELF depletion. We presume that an important function of NELF is to participate in stabilizing the Pol II-DSIF complex, resulting in a significant impact on transcription of its target genes. In order to directly link NELF to regulation of 20E-dependent genes in development, we show the presence of NELF at the promoters of 20E-dependent genes during their active transcription in both embryogenesis and metamorphosis. We also demonstrate that 20E-dependent promoters, while temporarily inactive at the larval stage, preserve a Pol II paused state and bind NELF complex.
Biases in ecological research: attitudes of scientists and ways of control
Authors: Zvereva Elena L. , Kozlov Mikhail V.
Published: January 2021

The properties of the human mind affect the quality of scientific knowledge through the insertion of unconscious biases during the research process. These biases frequently cause overestimation of the effects under study, thereby violating the reproducibility of the research and potentially leading to incorrect conclusions in subsequent research syntheses. We explored the level of knowledge about biases and attitudes to this problem by analysing 308 responses of ecology scientists to a specifically developed survey. We show that knowledge about biases and attitude towards biases depend on the scientist’s career stage, gender and affiliation country. Early career scientists are more concerned about biases, know more about measures to avoid biases, and twice more frequently have learned about biases from their university courses when compared with senior scientists. The respondents believe that their own studies are less prone to biases than are studies by other scientists, which hampers the control of biases in one’s own research. We conclude that education about biases is necessary, but not yet sufficient, to avoid biases because the unconscious origin of biases necessitates external intervention to combat them. Obligatory reporting of measures taken against biases in all relevant manuscripts will likely enhance the reproducibility of scientific results.
Longitudinal changes in retinal microvasculature after panretinal photocoagulation in diabetic retinopathy using swept-source OCT angiography
Authors: Kim Kiyoung , Kim Eung Suk , Yu Seung-Young
Published: January 2021

This study evaluated quantitative changes in microvascular parameters after panretinal photocoagulation (PRP) in diabetic retinopathy (DR), using swept-source OCT Angiography (SS-OCTA). A total of 27 treatment-naïve eyes were subjected to PRP and followed-up for > 12 months after the procedure. Foveal avascular zone (FAZ) area, macular perfusion density (PD), and vessel length density (VLD) were calculated on a 3 × 3 mm en face OCTA image and nonperfusion area (NPA) was obtained on a 12 × 12 mm en face OCTA image. One month after PRP, PD and VLD of superficial and deep capillary plexus decreased and subsequently, increased progressively across the next 12 months, with statistically significant differences (P = 0.015 and 0.02). Continuous decreasing trends in total NPA values was observed across 12 months after PRP (P = 0.125). A difference in PD of the superficial capillary plexus between baseline and 6 months post PRP, was significantly associated with the progression of DR, 12 months after PRP (OR 0.528; P = 0.025). We found significant longitudinal retinal microvascular changes after PRP in DR. Overall macular perfusion status was impaired and progressively recovered across the next 12 months, compared to the baseline. Additionally, the early treatment responses in PD can predict the long-term outcomes of PDR after PRP.
Spatial variations in the warming trend and the transition to more severe weather in midlatitudes
Authors: Estrada Francisco , Kim Dukpa , Perron Pierre
Published: January 2021

Due to various feedback processes called Arctic amplification, the high-latitudes’ response to increases in radiative forcing is much larger than elsewhere in the world, with a warming more than twice the global average. Since the 1990’s, this rapid warming of the Arctic was accompanied by no-warming or cooling over midlatitudes in the Northern Hemisphere in winter (the hiatus). The decrease in the thermal contrast between Arctic and midlatitudes has been connected to extreme weather events in midlatitudes via, e.g., shifts in the jet stream towards the equator and increases in the probability of high-latitude atmospheric blocking. Here we present an observational attribution study showing the spatial structure of the response to changes in radiative forcing. The results also connect the hiatus with diminished contrast between temperatures over regions in the Arctic and midlatitudes. Recent changes in these regional warming trends are linked to international actions such as the Montreal Protocol, and illustrate how changes in radiative forcing can trigger unexpected responses from the climate system. The lesson for climate policy is that human intervention with the climate is already large enough that even if stabilization was attained, impacts from an adjusting climate are to be expected.
Slow deformation event between large intraslab earthquakes at the Tonga Trench
Authors: Mitsui Yuta , Muramatsu Hinako , Tanaka Yusaku
Published: January 2021

Slow deformations associated with a subducting slab can affect quasi-static displacements and seismicity over a wide range of depths. Here, we analyse the seismotectonic activities in the Tonga subduction zone, which is the world’s most active area with regard to deep earthquakes. In our study, we combine data from global navigation satellite systems with an earthquake catalogue. We focus on the deep earthquakes that are below 400 km at the lower part of the Wadati–Benioff zone. We find that trenchward transient displacements and quiescence of deep earthquakes, in terms of background seismicity, were bounded in time by large intraslab earthquakes in 2009 and 2013. This “slow deformation event” between 2009 and 2013 may have been triggered by a distant and shallow M8.1 earthquake, which implies a slow slip event at the plate interface or a temporal acceleration of the subduction of the Pacific Plate. These findings provide new insights into the relationship between shallow and deep earthquakes in the subduction zone.
Passivation of InP solar cells using large area hexagonal-BN layers
Authors: Raj Vidur , Chugh Dipankar , Black Lachlan E. , Shehata M. M. , Li Li , Kremer Felipe , Macdonald Daniel H. , Tan Hark Hoe , Jagadish Chennupati
Published: January 2021

Surface passivation is crucial for many high-performance solid-state devices, especially solar cells. It has been proposed that 2D hexagonal boron nitride (hBN) films can provide near-ideal passivation due to their wide bandgap, lack of dangling bonds, high dielectric constant, and easy transferability to a range of substrates without disturbing their bulk properties. However, so far, the passivation of hBN has been studied for small areas, mainly because of its small sizes. Here, we report the passivation characteristics of wafer-scale, few monolayers thick, hBN grown by metalorganic chemical vapor deposition. Using a recently reported ITO/i-InP/p+-InP solar cell structure, we show a significant improvement in solar cell performance utilizing a few monolayers of hBN as the passivation layer. Interface defect density (at the hBN/i-InP) calculated using C–V measurement was 2 × 1012 eV−1cm−2 and was found comparable to several previously reported passivation layers. Thus, hBN may, in the future, be a possible candidate to achieve high-quality passivation. hBN-based passivation layers can mainly be useful in cases where the growth of lattice-matched passivation layers is complicated, as in the case of thin-film vapor–liquid–solid and close-spaced vapor transport-based III–V semiconductor growth techniques.
The role of device asymmetries and Schottky barriers on the helicity-dependent photoresponse of 2D phototransistors
Authors: Quereda Jorge , Hidding Jan , Ghiasi Talieh S. , van Wees Bart J. , van der Wal Caspar H. , Guimarães Marcos H. D.
Published: January 2021

Circular photocurrents (CPC), namely circular photogalvanic (CPGE) and photon drag effects, have recently been reported both in monolayer and multilayer transition metal dichalcogenide (TMD) phototransistors. However, the underlying physics for the emergence of these effects are not yet fully understood. In particular, the emergence of CPGE is not compatible with the D3h crystal symmetry of two-dimensional TMDs, and should only be possible if the symmetry of the electronic states is reduced by influences such as an external electric field or mechanical strain. Schottky contacts, nearly ubiquitous in TMD-based transistors, can provide the high electric fields causing a symmetry breaking in the devices. Here, we investigate the effect of these Schottky contacts on the CPC by characterizing the helicity-dependent photoresponse of monolayer MoSe2 devices both with direct metal-MoSe2 Schottky contacts and with h-BN tunnel barriers at the contacts. We find that, when Schottky barriers are present in the device, additional contributions to CPC become allowed, resulting in emergence of CPC for illumination at normal incidence.
Voltage-independent GluN2A-type NMDA receptor Ca2+ signaling promotes audiogenic seizures, attentional and cognitive deficits in mice
Authors: Bertocchi Ilaria , Eltokhi Ahmed , Rozov Andrey , Chi Vivan Nguyễn , Jensen Vidar , Bus Thorsten , Pawlak Verena , Serafino Marta , Sonntag Hannah , Yang Boyi , Burnashev Nail , Li Shi-Bin , Obenhaus Horst A. , Both Martin , Niewoehner Burkhard , Single Frank N. , Briese Michael , Boerner Thomas , Gass Peter , Rawlins John Nick P. , Köhr Georg , Bannerman David M. , Sprengel Rolf
Published: January 2021

The NMDA receptor-mediated Ca2+ signaling during simultaneous pre- and postsynaptic activity is critically involved in synaptic plasticity and thus has a key role in the nervous system. In GRIN2-variant patients alterations of this coincidence detection provoked complex clinical phenotypes, ranging from reduced muscle strength to epileptic seizures and intellectual disability. By using our gene-targeted mouse line (Grin2aN615S), we show that voltage-independent glutamate-gated signaling of GluN2A-containing NMDA receptors is associated with NMDAR-dependent audiogenic seizures due to hyperexcitable midbrain circuits. In contrast, the NMDAR antagonist MK-801-induced c-Fos expression is reduced in the hippocampus. Likewise, the synchronization of theta- and gamma oscillatory activity is lowered during exploration, demonstrating reduced hippocampal activity. This is associated with exploratory hyperactivity and aberrantly increased and dysregulated levels of attention that can interfere with associative learning, in particular when relevant cues and reward outcomes are disconnected in space and time. Together, our findings provide (i) experimental evidence that the inherent voltage-dependent Ca2+ signaling of NMDA receptors is essential for maintaining appropriate responses to sensory stimuli and (ii) a mechanistic explanation for the neurological manifestations seen in the NMDAR-related human disorders with GRIN2 variant-meidiated intellectual disability and focal epilepsy.
GPR109A mediates the effects of hippuric acid on regulating osteoclastogenesis and bone resorption in mice
Authors: Chen Jin-Ran , Zhao Haijun , Wankhade Umesh D. , Chintapalli Sree V. , Li Can , Gai Dongzheng , Shankar Kartik , Zhan Fenghuang , Lazarenko Oxana P.
Published: January 2021

The G protein-coupled receptor 109 A (GPR109A) is robustly expressed in osteoclastic precursor macrophages. Previous studies suggested that GPR109A mediates effects of diet-derived phenolic acids such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA) on promoting bone formation. However, the role of GPR109A in metabolic bone homeostasis and osteoclast differentiation has not been investigated. Using densitometric, bone histologic and molecular signaling analytic methods, we uncovered that bone mass and strength were significantly higher in tibia and spine of standard rodent diet weaned 4-week-old and 6-month-old GPR109A gene deletion (GPR109A−/−) mice, compared to their wild type controls. Osteoclast numbers in bone and in ex vivo bone marrow cell cultures were significantly decreased in GPR109A−/− mice compared to wild type controls. In accordance with these data, CTX-1 in bone marrow plasma and gene expression of bone resorption markers (TNFα, TRAP, Cathepsin K) were significantly decreased in GPR109A−/− mice, while on the other hand, P1NP was increased in serum from both male and female GPR109A−/− mice compared to their respective controls. GPR109A deletion led to suppressed Wnt/β-catenin signaling in osteoclast precursors to inhibit osteoclast differentiation and activity. Indeed, HA and 3-3-PPA substantially inhibited RANKL-induced GPR109A expression and Wnt/β-catenin signaling in osteoclast precursors and osteoclast differentiation. Resultantly, HA significantly inhibited bone resorption and increased bone mass in wild type mice, but had no additional effects on bone in GPR109A−/− mice compared with their respective untreated control mice. These results suggest an important role for GPR109A during osteoclast differentiation and bone resorption mediating effects of HA and 3-3-PPA on inhibiting bone resorption during skeletal development.
The spatial RNA integrity number assay for in situ evaluation of transcriptome quality
Authors: Kvastad Linda , Carlberg Konstantin , Larsson Ludvig , Villacampa Eva Gracia , Stuckey Alexander , Stenbeck Linnea , Mollbrink Annelie , Zamboni Margherita , Magnusson Jens Peter , Basmaci Elisa , Shamikh Alia , Prochazka Gabriela , Schaupp Anna-Lena , Borg Åke , Fugger Lars , Nistér Monica , Lundeberg Joakim
Published: January 2021

The RNA integrity number (RIN) is a frequently used quality metric to assess the completeness of rRNA, as a proxy for the corresponding mRNA in a tissue. Current methods operate at bulk resolution and provide a single average estimate for the whole sample. Spatial transcriptomics technologies have emerged and shown their value by placing gene expression into a tissue context, resulting in transcriptional information from all tissue regions. Thus, the ability to estimate RNA quality in situ has become of utmost importance to overcome the limitation with a bulk rRNA measurement. Here we show a new tool, the spatial RNA integrity number (sRIN) assay, to assess the rRNA completeness in a tissue wide manner at cellular resolution. We demonstrate the use of sRIN to identify spatial variation in tissue quality prior to more comprehensive spatial transcriptomics workflows.