bluuebunny/crossref_metadata_2025 huggingface dataset:
Loci-specific phase separation of FET fusion oncoproteins promotes gene transcription
Authors: Zuo Linyu , Zhang Guanwei , Massett Matthew , Cheng Jun , Guo Zicong , Wang Liang , Gao Yifei , Li Ru , Huang Xu , Li Pilong , Qi Zhi
Published: March 2021

Abnormally formed FUS/EWS/TAF15 (FET) fusion oncoproteins are essential oncogenic drivers in many human cancers. Interestingly, at the molecular level, they also form biomolecular condensates at specific loci. However, how these condensates lead to gene transcription and how features encoded in the DNA element regulate condensate formation remain unclear. Here, we develop an in vitro single-molecule assay to visualize phase separation on DNA. Using this technique, we observe that FET fusion proteins undergo phase separation at target binding loci and the phase separated condensates recruit RNA polymerase II and enhance gene transcription. Furthermore, we determine a threshold number of fusion-binding DNA elements that can enhance the formation of FET fusion protein condensates. These findings suggest that FET fusion oncoprotein promotes aberrant gene transcription through loci-specific phase separation, which may contribute to their oncogenic transformation ability in relevant cancers, such as sarcomas and leukemia.
Single cell transcriptomics reveals lineage trajectory of retinal ganglion cells in wild-type and Atoh7-null retinas
Authors: Wu Fuguo , Bard Jonathan E. , Kann Julien , Yergeau Donald , Sapkota Darshan , Ge Yichen , Hu Zihua , Wang Jie , Liu Tao , Mu Xiuqian
Published: March 2021

Atoh7 has been believed to be essential for establishing the retinal ganglion cell (RGC) lineage, and Pou4f2 and Isl1 are known to regulate RGC specification and differentiation. Here we report our further study of the roles of these transcription factors. Using bulk RNA-seq, we identify genes regulated by the three transcription factors, which expand our understanding of the scope of downstream events. Using scRNA-seq on wild-type and mutant retinal cells, we reveal a transitional cell state of retinal progenitor cells (RPCs) co-marked by Atoh7 and other genes for different lineages and shared by all early retinal lineages. We further discover the unexpected emergence of the RGC lineage in the absence of Atoh7. We conclude that competence of RPCs for different retinal fates is defined by lineage-specific genes co-expressed in the transitional state and that Atoh7 defines the RGC competence and collaborates with other factors to shepherd transitional RPCs to the RGC lineage.
Wildfire smoke impacts respiratory health more than fine particles from other sources: observational evidence from Southern California
Authors: Aguilera Rosana , Corringham Thomas , Gershunov Alexander , Benmarhnia Tarik
Published: March 2021

Wildfires are becoming more frequent and destructive in a changing climate. Fine particulate matter, PM2.5, in wildfire smoke adversely impacts human health. Recent toxicological studies suggest that wildfire particulate matter may be more toxic than equal doses of ambient PM2.5. Air quality regulations however assume that the toxicity of PM2.5 does not vary across different sources of emission. Assessing whether PM2.5 from wildfires is more or less harmful than PM2.5 from other sources is a pressing public health concern. Here, we isolate the wildfire-specific PM2.5 using a series of statistical approaches and exposure definitions. We found increases in respiratory hospitalizations ranging from 1.3 to up to 10% with a 10 μg m−3 increase in wildfire-specific PM2.5, compared to 0.67 to 1.3% associated with non-wildfire PM2.5. Our conclusions point to the need for air quality policies to consider the variability in PM2.5 impacts on human health according to the sources of emission.
Single-cell measurement of plasmid copy number and promoter activity
Authors: Shao Bin , Rammohan Jayan , Anderson Daniel A. , Alperovich Nina , Ross David , Voigt Christopher A.
Published: March 2021

Accurate measurements of promoter activities are crucial for predictably building genetic systems. Here we report a method to simultaneously count plasmid DNA, RNA transcripts, and protein expression in single living bacteria. From these data, the activity of a promoter in units of RNAP/s can be inferred. This work facilitates the reporting of promoters in absolute units, the variability in their activity across a population, and their quantitative toll on cellular resources, all of which provide critical insights for cellular engineering.
Hyocholic acid species as novel biomarkers for metabolic disorders
Authors: Zheng Xiaojiao , Chen Tianlu , Zhao Aihua , Ning Zhangchi , Kuang Junliang , Wang Shouli , You Yijun , Bao Yuqian , Ma Xiaojing , Yu Haoyong , Zhou Jian , Jiang Miao , Li Mengci , Wang Jieyi , Ma Xiaohui , Zhou Shuiping , Li Yitao , Ge Kun , Rajani Cynthia , Xie Guoxiang , Hu Cheng , Guo Yike , Lu Aiping , Jia Weiping , Jia Wei
Published: March 2021

Hyocholic acid (HCA) is a major bile acid (BA) species in the BA pool of pigs, a species known for its exceptional resistance to spontaneous development of diabetic phenotypes. HCA and its derivatives are also present in human blood and urine. We investigate whether human HCA profiles can predict the development of metabolic disorders. We find in the first cohort (n = 1107) that both obesity and diabetes are associated with lower serum concentrations of HCA species. A separate cohort study (n = 91) validates this finding and further reveals that individuals with pre-diabetes are associated with lower levels of HCA species in feces. Serum HCA levels increase in the patients after gastric bypass surgery (n = 38) and can predict the remission of diabetes two years after surgery. The results are replicated in two independent, prospective cohorts (n = 132 and n = 207), where serum HCA species are found to be strong predictors for metabolic disorders in 5 and 10 years, respectively. These findings underscore the association of HCA species with diabetes, and demonstrate the feasibility of using HCA profiles to assess the future risk of developing metabolic abnormalities.
psiCLIP reveals dynamic RNA binding by DEAH-box helicases before and after exon ligation
Authors: Strittmatter Lisa M. , Capitanchik Charlotte , Newman Andrew J. , Hallegger Martina , Norman Christine M. , Fica Sebastian M. , Oubridge Chris , Luscombe Nicholas M. , Ule Jernej , Nagai Kiyoshi
Published: March 2021

RNA helicases remodel the spliceosome to enable pre-mRNA splicing, but their binding and mechanism of action remain poorly understood. To define helicase-RNA contacts in specific spliceosomal states, we develop purified spliceosome iCLIP (psiCLIP), which reveals dynamic helicase-RNA contacts during splicing catalysis. The helicase Prp16 binds along the entire available single-stranded RNA region between the branchpoint and 3′-splice site, while Prp22 binds diffusely downstream of the branchpoint before exon ligation, but then switches to more narrow binding in the downstream exon after exon ligation, arguing against a mechanism of processive translocation. Depletion of the exon-ligation factor Prp18 destabilizes Prp22 binding to the pre-mRNA, suggesting that proofreading by Prp22 may sense the stability of the spliceosome during exon ligation. Thus, psiCLIP complements structural studies by providing key insights into the binding and proofreading activity of spliceosomal RNA helicases.
The stability of subducted glaucophane with the Earth’s secular cooling
Authors: Bang Yoonah , Hwang Huijeong , Kim Taehyun , Cynn Hyunchae , Park Yong , Jung Haemyeong , Park Changyong , Popov Dmitry , Prakapenka Vitali B. , Wang Lin , Liermann Hanns-Peter , Irifune Tetsuo , Mao Ho-Kwang , Lee Yongjae
Published: March 2021

The blueschist to eclogite transition is one of the major geochemical–metamorphic processes typifying the subduction zone, which releases fluids triggering earthquakes and arc volcanism. Although glaucophane is an index hydrous mineral for the blueschist facies, its stability at mantle depths in diverse subduction regimes of contemporary and early Earth has not been experimentally determined. Here, we show that the maximum depth of glaucophane stability increases with decreasing thermal gradients of the subduction system. Along cold subduction geotherm, glaucophane remains stable down ca. 240 km depth, whereas it dehydrates and breaks down at as shallow as ca. 40 km depth under warm subduction geotherm or the Proterozoic tectonic setting. Our results imply that secular cooling of the Earth has extended the stability of glaucophane and consequently enabled the transportation of water into deeper interior of the Earth, suppressing arc magmatism, volcanism, and seismic activities along subduction zones.
Contrasting long-term temperature trends reveal minor changes in projected potential evapotranspiration in the US Midwest
Authors: Basso Bruno , Martinez-Feria Rafael A. , Rill Lydia , Ritchie Joe T.
Published: March 2021

Warming generally leads to increased evaporative demand, altering the amount of water needed for growing crops. For the Midwest, some studies have suggested that reaching yield targets by 2050 will not be possible without additional precipitation or large expansion of irrigation. Here, we show that this claim is not supported by the historical summer climate trends, which indicate that the warming of daily average temperatures is largely driven by increases in minimum temperatures, while maximum temperatures have decreased. This has translated into a net decrease in vapor pressure deficit (VPD) and potential evapotranspiration (PET). With the increasing rainfall, this suggests that crop water deficits have likely become less frequent in the region despite the warming climate. By projecting these trends into 2050 and ancillary use of a crop model, we estimate minor changes in PET that would have minimal effects on corn yields (<6%) under persistence of these trends.
Inherently confinable split-drive systems in Drosophila
Authors: Terradas Gerard , Buchman Anna B. , Bennett Jared B. , Shriner Isaiah , Marshall John M. , Akbari Omar S. , Bier Ethan
Published: March 2021

CRISPR-based gene-drive systems, which copy themselves via gene conversion mediated by the homology-directed repair (HDR) pathway, have the potential to revolutionize vector control. However, mutant alleles generated by the competing non-homologous end-joining (NHEJ) pathway, resistant to Cas9 cleavage, can interrupt the spread of gene-drive elements. We hypothesized that drives targeting genes essential for viability or reproduction also carrying recoded sequences that restore endogenous gene functionality should benefit from dominantly-acting maternal clearance of NHEJ alleles combined with recessive Mendelian culling processes. Here, we test split gene-drive (sGD) systems in Drosophila melanogaster that are inserted into essential genes required for viability (rab5, rab11, prosalpha2) or fertility (spo11). In single generation crosses, sGDs copy with variable efficiencies and display sex-biased transmission. In multigenerational cage trials, sGDs follow distinct drive trajectories reflecting their differential tendencies to induce target chromosome damage and/or lethal/sterile mosaic Cas9-dependent phenotypes, leading to inherently confinable drive outcomes.
Author Correction: Ionic shape-morphing microrobotic end-effectors for environmentally adaptive targeting, releasing, and sampling
Authors: Zheng Zhiqiang , Wang Huaping , Dong Lixin , Shi Qing , Li Jianing , Sun Tao , Huang Qiang , Fukuda Toshio
Published: March 2021

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21986-8
Prediction of crossing nodal-lines and large intrinsic spin Hall conductivity in topological Dirac semimetal Ta3As family
Authors: Hou Wenjie , Liu Jian , Zuo Xi , Xu Jian , Zhang Xueying , Liu Desheng , Zhao Mingwen , Zhu Zhen-Gang , Luo Hong-Gang , Zhao Weisheng
Published: March 2021

Topological insulators (TIs) are considered as ideal platforms for generating large spin Hall conductivity (SHC), however, the bulk carrier problem, which is unavoidable in TIs, hinders their practical applications. Recently, topological semimetals (TSMs) have been proposed to achieve large SHC to replace TIs. However, the ideal TSM candidates with large SHC are still lacking. In terms of first-principles calculations, we predict that Ta3As family compounds exhibit complex crossing nodal-lines (CNL) properties in absence of the spin-orbit coupling (SOC). However, they transfer to Dirac TSMs under the influence of strong SOC, and present large SHC around Fermi level in particular. Remarkably, the SHC value of Ta3Y (Y = As, Sb, Bi) is around 1500–1700 $$(\hbar /e)({\mathrm{{\Omega}}} \cdot {\mathrm{cm}})^{ - 1}$$

(

ħ
/
e

)

(

Ω
⋅
cm

)

−
1

, which is comparable to noble metal Pt and much larger than TIs, Weyl TSMs, and 4d/5d transition metals. Our work not only suggests a kind of TSM family with interesting Dirac CNL around Fermi level, but also paves the way for searching large intrinsic SHC materials in complex CNL TSM systems.
The Prostate Health Index aids multi-parametric MRI in diagnosing significant prostate cancer
Authors: Fan Yu-Hua , Pan Po-Hsun , Cheng Wei-Ming , Wang Hsin-Kai , Shen Shu-Huei , Liu Hsian-Tzu , Cheng Hao-Min , Chen Wei-Ren , Huang Tzu-Hao , Wei Tzu-Chun , Huang I-Shen , Lin Chih-Chieh , Huang Eric Y. H. , Chung Hsiao-Jen , Huang William J. S. , Lin Tzu-Ping
Published: March 2021

To evaluate the performance of the Prostate Health Index (PHI) in magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion prostate biopsy for the detection of clinically significant prostate cancer (csPCa). We prospectively enrolled 164 patients with at least one Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) ≥ 3 lesions who underwent MRI-TRUS fusion prostate biopsy. Of the PSA-derived biomarkers, the PHI had the best performance in predicting csPCa (AUC 0.792, CI 0.707–0.877) in patients with PI-RADS 4/5 lesions. Furthermore, the predictive power of PHI was even higher in the patients with PI-RADS 3 lesions (AUC 0.884, CI 0.792–0.976). To minimize missing csPCa, we used a PHI cutoff of 27 and 7.4% of patients with PI-RADS 4/5 lesions could have avoided a biopsy. At this level, 2.0% of cases with csPCa would have been missed, with sensitivity and NPV rates of 98.0% and 87.5%, respectively. However, the subgroup of PI-RADS 3 was too small to define the optimal PHI cutoff. PHI was the best PSA-derived biomarker to predict csPCa in MRI-TRUS fusion prostate biopsies in men with PI-RADS ≥ 3 lesions, especially for the patients with PI-RADS 3 lesions who gained the most value.
RETRACTED ARTICLE: Stay-at-home policy is a case of exception fallacy: an internet-based ecological study
Authors: Savaris R. F. , Pumi G. , Dalzochio J. , Kunst R.
Published: March 2021

A recent mathematical model has suggested that staying at home did not play a dominant role in reducing COVID-19 transmission. The second wave of cases in Europe, in regions that were considered as COVID-19 controlled, may raise some concerns. Our objective was to assess the association between staying at home (%) and the reduction/increase in the number of deaths due to COVID-19 in several regions in the world. In this ecological study, data fromwww.google.com/covid19/mobility/, ourworldindata.org and covid.saude.gov.br were combined. Countries with > 100 deaths and with a Healthcare Access and Quality Index of ≥ 67 were included. Data were preprocessed and analyzed using the difference between number of deaths/million between 2 regions and the difference between the percentage of staying at home. The analysis was performed using linear regression with special attention to residual analysis. After preprocessing the data, 87 regions around the world were included, yielding 3741 pairwise comparisons for linear regression analysis. Only 63 (1.6%) comparisons were significant. With our results, we were not able to explain if COVID-19 mortality is reduced by staying at home in ~ 98% of the comparisons after epidemiological weeks 9 to 34.
Competence-based social status and implicit preference modulate the ability to coordinate during a joint grasping task
Authors: Boukarras Sarah , Era Vanessa , Aglioti Salvatore Maria , Candidi Matteo
Published: March 2021

Studies indicate that social status influences people’s social perceptions. Less information is available about whether induced social status influences dyadic coordination during motor interactions. To explore this issue, we designed a study in which two confederates obtained high or low competence-based status by playing a game together with the participant, while the participant always occupied the middle position of the hierarchy. Following this status-inducing phase, participants were engaged in a joint grasping task with the high- and low-status confederates in different sessions while behavioural (i.e., interpersonal asynchrony and movement start time) indexes were measured. Participants’ performance in the task (i.e., level of interpersonal asynchrony) when interacting with the low-status partner was modulated by their preference for him. The lower participants’ preference for a low- relative to a high-status confederate, the worse participants’ performance when interacting with the low-status confederate. Our results show that participants’ performance during motor interactions changes according to the social status of the interaction partner.
A systematic review and meta-analysis of the hip capsule innervation and its clinical implications
Authors: Tomlinson Joanna , Ondruschka Benjamin , Prietzel Torsten , Zwirner Johann , Hammer Niels
Published: March 2021

Detailed understanding of the innervation of the hip capsule (HC) helps inform surgeons’ and anaesthetists’ clinical practice. Post-interventional pain following radiofrequency nerve ablation (RFA) and dislocation following total hip arthroplasty (THA) remain poorly understood, highlighting the need for more knowledge on the topic. This systematic review and meta-analysis focuses on gross anatomical studies investigating HC innervation. The main outcomes were defined as the prevalence, course, density and distribution of the nerves innervating the HC and changes according to demographic variables. HC innervation is highly variable; its primary nerve supply seems to be from the nerve to quadratus femoris and obturator nerve. Many articular branches originated from muscular branches of the lumbosacral plexus. It remains unclear whether demographic or anthropometric variables may help predict potential differences in HC innervation. Consequently, primary targets for RFA should be the anterior inferomedial aspect of the HC. For THA performed on non-risk patients, the posterior approach with capsular repair appears to be most appropriate with the lowest risk of articular nerve damage. Care should also be taken to avoid damaging vessels and muscles of the hip joint. Further investigation is required to form a coherent map of HC innervation, utilizing combined gross and histological investigation.
Postpartum ovulation and early pregnancy in the menstruating spiny mouse, Acomys cahirinus
Authors: McKenna Jarrod , Bellofiore Nadia , Dimitriadis Evdokia , Temple-Smith Peter
Published: March 2021

Egyptian spiny mice are the only known species to have human-like menstruation and a postpartum ovulation. Unfortunately, no endocrine or morphological evidence has been provided for a postpartum ovulation in spiny mice, and while later stages of pregnancy have been well studied, early events including embryo implantation and spiral artery remodelling have not been reported. This study compared the sex steroid endocrinology and reproductive tract morphology of dams at eight timepoints (n = 40) postpartum to determine the timing of ovulation and the timing and invasiveness of embryo implantation in A. cahirinus. Reproductive tracts were fixed and stained for histology and immunohistochemistry, and plasma was prepared for enzyme-linked immunosorbent assay. Ovarian histology and estradiol-17B concentrations indicate ovulation within 48 h of parturition and then immediate resumption of follicular growth. Uterine histology and immunohistochemistry revealed progressive epithelial repair, endometrial growth and spiral artery assembly and remodelling in dams postpartum. Blastocysts were seen in the uterine lumen at day 4–5 postpartum and embryos had implanted superficially with minimal stromal invasion by day 5–6. This study provides further evidence for the unique, humanesque reproductive biology of spiny mice and for a postpartum ovulation using endocrine and morphological changes observed during early pregnancy. Taken together, our data suggest that spiny mice may act as appropriate models of human pregnancy disorders such as implantation failure or pre-eclampsia.
Exchange biased delta-E effect enables the detection of low frequency pT magnetic fields with simultaneous localization
Authors: Spetzler B. , Bald C. , Durdaut P. , Reermann J. , Kirchhof C. , Teplyuk A. , Meyners D. , Quandt E. , Höft M. , Schmidt G. , Faupel F.
Published: March 2021

Delta-E effect sensors are based on magnetoelectric resonators that detune in a magnetic field due to the delta-E effect of the magnetostrictive material. In recent years, such sensors have shown the potential to detect small amplitude and low-frequency magnetic fields. Yet, they all require external magnetic bias fields for optimal operation, which is highly detrimental to their application. Here, we solve this problem by combining the delta-E effect with exchange biased multilayers and operate the resonator in a low-loss torsion mode. It is comprehensively analyzed experimentally and theoretically using various kinds of models. Due to the exchange bias, no external magnetic bias fields are required, but still low detection limits down to $${{\text{350 pT}} \mathord{\left/ {\vphantom {{\text{350 pT}} {\sqrt {{\text{Hz}}} }}} \right. \kern-\nulldelimiterspace} {\sqrt {{\text{Hz}}} }}$$

350 pT

/

Hz

at 25 Hz are achieved. The potential of this concept is demonstrated with a new operating scheme that permits simultaneous measurement and localization, which is especially desirable for typical biomedical inverse solution problems. The sensor is localized with a minimum spatial resolution of 1 cm while measuring a low-frequency magnetic test signal that can be well reconstructed. Overall, we demonstrate that this class of magnetic field sensors is a significant step towards first biomedical applications and compact large number sensor arrays.
AI-based localization and classification of skin disease with erythema
Authors: Son Ha Min , Jeon Wooho , Kim Jinhyun , Heo Chan Yeong , Yoon Hye Jin , Park Ji-Ung , Chung Tai-Myoung
Published: March 2021

Although computer-aided diagnosis (CAD) is used to improve the quality of diagnosis in various medical fields such as mammography and colonography, it is not used in dermatology, where noninvasive screening tests are performed only with the naked eye, and avoidable inaccuracies may exist. This study shows that CAD may also be a viable option in dermatology by presenting a novel method to sequentially combine accurate segmentation and classification models. Given an image of the skin, we decompose the image to normalize and extract high-level features. Using a neural network-based segmentation model to create a segmented map of the image, we then cluster sections of abnormal skin and pass this information to a classification model. We classify each cluster into different common skin diseases using another neural network model. Our segmentation model achieves better performance compared to previous studies, and also achieves a near-perfect sensitivity score in unfavorable conditions. Our classification model is more accurate than a baseline model trained without segmentation, while also being able to classify multiple diseases within a single image. This improved performance may be sufficient to use CAD in the field of dermatology.
Novel nanotech antioxidant cocktail prevents medical diagnostic procedures ionizing radiation effects
Authors: Gorenberg Miguel , Agbarya Abed , Groshar David , Volovik Ilya , Avitan Ofir , Sukhotnik Igor
Published: March 2021

Ionizing radiation (IR) exposure results in oxidative damage causing cytotoxic and genotoxic effects. Double-strand breaks (DSBs) are considered the most significant DNA lesions induced by ionizing radiation. The present study evaluates the radio protective effect of a novel antioxidant cocktail through quantification of DSB in peripheral blood lymphocytes (PBL) in vivo. The study included 16 consecutive patients who were divided into 2 groups, 6 patients received the novel antioxidant cocktail and 10 control patients. Blood samples were drawn from the patients undergoing bone scan, before the injection of the 99mTc MDP tracer and 2 h after the injection. Quantification of the IR damage was done by Immunofluorescence analysis of the phosphorylated histone, γ-H2AX, used to monitor DSB induction and repair in PBL. The radiation effect of the control group was measured by 2 variables, the average DBSs foci per nucleus and the percent of the DSB bearing cells in PBL. The findings showed a significant increase in the DSBs after isotope injection with an average increment of 0.29 ± 0.13 of foci/nucleus and 17.07% ± 7.68 more DSB bearing cells (p < 0.05). The cocktail treated group showed a lower difference average of − 2.79% ± 6.13 DSB bearing cells. A paired t-test revealed a significant difference between the groups (p < 0.005) confirming the cocktail’s protective effect. The novel anti-oxidant treatment decreases the oxidative stress-induced DNA damage and can be considered as a preventative treatment before radiation exposure.
Potential of garnet sand as an unconventional resource of the critical high-technology metals scandium and rare earth elements
Authors: Klimpel Franziska , Bau Michael , Graupner Torsten
Published: March 2021

Scandium is a critical raw material that is essential for the EU economy because of its potential application in enabling technologies such as fuel cells and lightweight materials. As there is currently no secure supply of Sc, several projects worldwide evaluate potential Sc sources. While elsewhere in Europe emphasis is placed upon secondary resources such as red mud, we investigated the potential of industrial garnet sand and its waste products. Since Sc readily substitutes for Mg and Fe in the crystal lattice of garnet, the garnet minerals almandine and pyrope, in particular, may show high Sc concentrations. Garnet sand, after being used as an abrasive in the cutting and sandblasting industry, is recycled several times before it is finally considered waste which eventually must be disposed of. Extraction of Sc (and rare earth elements, REE) from such garnet sand may generate added value and thereby reduce disposal cost. The studied garnet sands from different mines in Australia, India and the U.S., and industrial garnet sands commercially available in Germany from different suppliers show average Sc concentrations of 93.7 mg/kg and 90.7 mg/kg, respectively, i.e. similar to red mud. Our data also show that “fresh” and recycled garnet sands yield similar Sc concentrations. Within the framework of a minimum-waste approach, it may be feasible to utilize the industrial waste-product “garnet sand” as an unconventional source of Sc and REE, that reduces disposal cost.
Soil microbial and nutrient dynamics under different sowings environment of Indian mustard (Brassica juncea L.) in rice based cropping system
Authors: Kumar Sunil , Meena Ram Swaroop , Singh Rakesh Kumar , Munir Tariq Muhammad , Datta Rahul , Danish Subhan , Yadav Gulab Singh , Kumar Sandeep
Published: March 2021

Farmers are not growing diversified crops and applying huge amounts of agrochemicals and imbalanced fertilizers in the rice-wheat cropping system (RWCS), since the 1960s. The objective of this study was to evaluate the microbial and nutrient dynamics in Indian mustard (Brassica juncea L.) under various sowing environments and nutrient sources duringRabiseason (October–March), 2015–2016. The experiment was laid out in the split-plot design with three sowing dates in main-plots, and eight nutrient sources in sub-plots. The maximum bacteria, fungi, and actinomycetes population, soil microbial biomass carbon (SMBC), dehydrogenase activities, and available nitrogen, phosphorus, potassium, and sulphur (NPKS) were recorded on November 17 sown crop, and the lowest was observed on December 7 sowing during both the years, and in the pooled analysis. Furthermore, applied nutrient sources, highest bacteria, fungi, and actinomycetes population, available NPKS, SMBC, and dehydrogenase activity were observed in 75% recommended dose of fertilizers (RDF) + 25% N through pressmud (PM) + Azotobacto + phosphorus solubilizing bacteria(PSB) than other nutrient sources. In conclusion, high demand and cost of chemical fertilizers can be replaced by 25% amount easily and locally available organic manures like PM compost to sustain the soil health and crop productivity. It will be helpful to restore the soil biodiversity in the RWCS and provide a roadmap for the researchers, government planners, and policymakers for the use of PM as a source of organic matter and nutrients.
DSS-induced colitis is associated with adipose tissue dysfunction and disrupted hepatic lipid metabolism leading to hepatosteatosis and dyslipidemia in mice
Authors: Kwon Jeonghyeon , Lee Chungho , Heo Sungbaek , Kim Bobae , Hyun Chang-Kee
Published: March 2021

Considering high prevalence of non-alcoholic fatty liver diseases (NAFLD) in patients with inflammatory bowel disease (IBD), this study aimed to elucidate molecular mechanisms for how intestinal inflammatory conditions are causally linked to hepatic steatosis and dyslipidemia. Both younger and older mice treated with acute or chronic dextran sodium sulfate (DSS) developed colitis, which was evidenced by weight loss, colon length shortening, and elevated disease activity index and inflammation score. They also showed decreased expression of intestinal barrier function-related proteins and elevated plasma lipopolysaccharide level, indicating DSS-induced barrier dysfunction and thereby increased permeability. Interestingly, they displayed phenotypes of hepatic fat accumulation and abnormal blood lipid profiles. This DSS-induced colitis-associated lipid metabolic dysfunction was due to overall disruption of metabolic processes including fatty acid oxidation, lipogenesis, lipolysis, reverse cholesterol transport, bile acid synthesis, and white adipose tissue browning and brown adipose tissue thermogenesis, most of which are mediated by key regulators of energy homeostasis such as FGF21, adiponectin, and irisin, via SIRT1/PGC-1α- and LXRα-dependent pathways. Our study suggests a potential molecular mechanism underlying the comorbidity of NAFLD and IBD, which could provide a key to understanding how the two diseases are pathogenically linked and discovering critical therapeutic targets for their treatment.
Outcome of endovascular treatment within and beyond 6 h without perfusion software
Authors: Jing Zhen , Li Hao , Huang Shengming , Guan Min , Li Yongxin , Lu Kui , Wu Jianzhou , Zhong Wangtao , Huang Li’an
Published: March 2021

Endovascular treatment (EVT) has been accepted as the standard of care for patients with acute ischemic stroke. The aim of the present study was to compare clinical outcomes of patients who received EVT within and beyond 6 h from symptom onset to groin puncture without perfusion software in Guangdong district, China. Between March 2017 and May 2018, acute ischemic stroke patients who received EVT from 6 comprehensive stroke centers, were enrolled into the registry study. In this subgroup study, we included all patients who had acute proximal large vessel occlusion in the anterior circulation. The demographic, clinical and neuroimaging data were collected from each center. A total of 192 patients were included in this subgroup study. They were divided into two groups: group A (n = 125), within 6 h; group B (n = 67), 6–24 h from symptom onset to groin puncture. There were no substantial differences between these two groups in terms of 90 days favorable outcome (modified Rankin scale [mRS] ≤ 2, P = 0.051) and mortality (P = 0.083), and the risk of symptomatic intracranial hemorrhage at 24 h (P = 0.425). The NIHSS (median 16, IQR12-20, group A; median 12, IQR8-18, group B; P = 0.009) and ASPECTS (median 10, IQR8-10, group A; median 9, IQR8-10, group B; P = 0.034) at baseline were higher in group A. The anesthesia method (general anesthesia, 21.3%, group A vs. 1.5% group B, P = 0.001) were also statistically different between the two groups. The NIHSS and ASPECTS were higher, and general anesthesia was also more widely used in group A. Clinical outcomes were not significantly different within 6 h versus 6–24 h from symptom onset to groin puncture in this real world study.
Deep-learning system to improve the quality and efficiency of volumetric heart segmentation for breast cancer
Authors: Zeleznik Roman , Weiss Jakob , Taron Jana , Guthier Christian , Bitterman Danielle S. , Hancox Cindy , Kann Benjamin H. , Kim Daniel W. , Punglia Rinaa S. , Bredfeldt Jeremy , Foldyna Borek , Eslami Parastou , Lu Michael T. , Hoffmann Udo , Mak Raymond , Aerts Hugo J. W. L.
Published: March 2021

Although artificial intelligence algorithms are often developed and applied for narrow tasks, their implementation in other medical settings could help to improve patient care. Here we assess whether a deep-learning system for volumetric heart segmentation on computed tomography (CT) scans developed in cardiovascular radiology can optimize treatment planning in radiation oncology. The system was trained using multi-center data (n = 858) with manual heart segmentations provided by cardiovascular radiologists. Validation of the system was performed in an independent real-world dataset of 5677 breast cancer patients treated with radiation therapy at the Dana-Farber/Brigham and Women’s Cancer Center between 2008–2018. In a subset of 20 patients, the performance of the system was compared to eight radiation oncology experts by assessing segmentation time, agreement between experts, and accuracy with and without deep-learning assistance. To compare the performance to segmentations used in the clinic, concordance and failures (defined as Dice < 0.85) of the system were evaluated in the entire dataset. The system was successfully applied without retraining. With deep-learning assistance, segmentation time significantly decreased (4.0 min [IQR 3.1–5.0] vs. 2.0 min [IQR 1.3–3.5]; p < 0.001), and agreement increased (Dice 0.95 [IQR = 0.02]; vs. 0.97 [IQR = 0.02], p < 0.001). Expert accuracy was similar with and without deep-learning assistance (Dice 0.92 [IQR = 0.02] vs. 0.92 [IQR = 0.02]; p = 0.48), and not significantly different from deep-learning-only segmentations (Dice 0.92 [IQR = 0.02]; p ≥ 0.1). In comparison to real-world data, the system showed high concordance (Dice 0.89 [IQR = 0.06]) across 5677 patients and a significantly lower failure rate (p < 0.001). These results suggest that deep-learning algorithms can successfully be applied across medical specialties and improve clinical care beyond the original field of interest.
Recent genetic connectivity and clinal variation in chimpanzees
Authors: Lester Jack D. , Vigilant Linda , Gratton Paolo , McCarthy Maureen S. , Barratt Christopher D. , Dieguez Paula , Agbor Anthony , Álvarez-Varona Paula , Angedakin Samuel , Ayimisin Emmanuel Ayuk , Bailey Emma , Bessone Mattia , Brazzola Gregory , Chancellor Rebecca , Cohen Heather , Danquah Emmanuel , Deschner Tobias , Egbe Villard Ebot , Eno-Nku Manasseh , Goedmakers Annemarie , Granjon Anne-Céline , Head Josephine , Hedwig Daniela , Hernandez-Aguilar R. Adriana , Jeffery Kathryn J. , Jones Sorrel , Junker Jessica , Kadam Parag , Kaiser Michael , Kalan Ammie K. , Kehoe Laura , Kienast Ivonne , Langergraber Kevin E. , Lapuente Juan , Laudisoit Anne , Lee Kevin , Marrocoli Sergio , Mihindou Vianet , Morgan David , Muhanguzi Geoffrey , Neil Emily , Nicholl Sonia , Orbell Christopher , Ormsby Lucy Jayne , Pacheco Liliana , Piel Alex , Robbins Martha M. , Rundus Aaron , Sanz Crickette , Sciaky Lilah , Siaka Alhaji M. , Städele Veronika , Stewart Fiona , Tagg Nikki , Ton Els , van Schijndel Joost , Vyalengerera Magloire Kambale , Wessling Erin G. , Willie Jacob , Wittig Roman M. , Yuh Yisa Ginath , Yurkiw Kyle , Zuberbuehler Klaus , Boesch Christophe , Kühl Hjalmar S. , Arandjelovic Mimi
Published: March 2021

Much like humans, chimpanzees occupy diverse habitats and exhibit extensive behavioural variability. However, chimpanzees are recognized as a discontinuous species, with four subspecies separated by historical geographic barriers. Nevertheless, their range-wide degree of genetic connectivity remains poorly resolved, mainly due to sampling limitations. By analyzing a geographically comprehensive sample set amplified at microsatellite markers that inform recent population history, we found that isolation by distance explains most of the range-wide genetic structure of chimpanzees. Furthermore, we did not identify spatial discontinuities corresponding with the recognized subspecies, suggesting that some of the subspecies-delineating geographic barriers were recently permeable to gene flow. Substantial range-wide genetic connectivity is consistent with the hypothesis that behavioural flexibility is a salient driver of chimpanzee responses to changing environmental conditions. Finally, our observation of strong local differentiation associated with recent anthropogenic pressures portends future loss of critical genetic diversity if habitat fragmentation and population isolation continue unabated.
Engineering subtilisin proteases that specifically degrade active RAS
Authors: Chen Yingwei , Toth Eric A. , Ruan Biao , Choi Eun Jung , Simmerman Richard , Chen Yihong , He Yanan , Wang Ruixue , Godoy-Ruiz Raquel , King Harlan , Custer Gregory , Travis Gallagher D. , Rozak David A. , Solomon Melani , Muro Silvia , Weber David J. , Orban John , Fuerst Thomas R. , Bryan Philip N.
Published: March 2021

We describe the design, kinetic properties, and structures of engineered subtilisin proteases that degrade the active form of RAS by cleaving a conserved sequence in switch 2. RAS is a signaling protein that, when mutated, drives a third of human cancers. To generate high specificity for the RAS target sequence, the active site was modified to be dependent on a cofactor (imidazole or nitrite) and protease sub-sites were engineered to create a linkage between substrate and cofactor binding. Selective proteolysis of active RAS arises from a 2-step process wherein sub-site interactions promote productive binding of the cofactor, enabling cleavage. Proteases engineered in this way specifically cleave active RAS in vitro, deplete the level of RAS in a bacterial reporter system, and also degrade RAS in human cell culture. Although these proteases target active RAS, the underlying design principles are fundamental and will be adaptable to many target proteins.
The gut mycobiome of healthy mice is shaped by the environment and correlates with metabolic outcomes in response to diet
Authors: Mims Tahliyah S. , Abdallah Qusai Al , Stewart Justin D. , Watts Sydney P. , White Catrina T. , Rousselle Thomas V. , Gosain Ankush , Bajwa Amandeep , Han Joan C. , Willis Kent A. , Pierre Joseph F.
Published: March 2021

As an active interface between the host and their diet, the gut microbiota influences host metabolic adaptation; however, the contributions of fungi have been overlooked. Here, we investigate whether variations in gut mycobiome abundance and composition correlate with key features of host metabolism. We obtained animals from four commercial sources in parallel to test if differing starting mycobiomes can shape host adaptation in response to processed diets. We show that the gut mycobiome of healthy mice is shaped by the environment, including diet, and significantly correlates with metabolic outcomes. We demonstrate that exposure to processed diet leads to persistent differences in fungal communities that significantly associate with differential deposition of body mass in male mice compared to mice fed standardized diet. Fat deposition in the liver, transcriptional adaptation of metabolically active tissues and serum metabolic biomarker levels are linked with alterations in fungal community diversity and composition. Specifically, variation in fungi from the generaThermomycesandSaccharomycesmost strongly associate with metabolic disturbance and weight gain. These data suggest that host–microbe metabolic interactions may be influenced by variability in the mycobiome. This work highlights the potential significance of the gut mycobiome in health and has implications for human and experimental metabolic studies.
Hyperthermophilic methanogenic archaea act as high-pressure CH4 cell factories
Authors: Mauerhofer Lisa-Maria , Zwirtmayr Sara , Pappenreiter Patricia , Bernacchi Sébastien , Seifert Arne H. , Reischl Barbara , Schmider Tilman , Taubner Ruth-Sophie , Paulik Christian , Rittmann Simon K.-M. R.
Published: March 2021

Bioprocesses converting carbon dioxide with molecular hydrogen to methane (CH4) are currently being developed to enable a transition to a renewable energy production system. In this study, we present a comprehensive physiological and biotechnological examination of 80 methanogenic archaea (methanogens) quantifying growth and CH4 production kinetics at hyperbaric pressures up to 50 bar with regard to media, macro-, and micro-nutrient supply, specific genomic features, and cell envelope architecture. Our analysis aimed to systematically prioritize high-pressure and high-performance methanogens. We found that the hyperthermophilic methanococci Methanotorris igneus and Methanocaldococcoccus jannaschii are high-pressure CH4 cell factories. Furthermore, our analysis revealed that high-performance methanogens are covered with an S-layer, and that they harbour the amino acid motif Tyrα444 Glyα445 Tyrα446 in the alpha subunit of the methyl-coenzyme M reductase. Thus, high-pressure biological CH4 production in pure culture could provide a purposeful route for the transition to a carbon-neutral bioenergy sector.
Diselenide crosslinks for enhanced and simplified oxidative protein folding
Authors: Mousa Reem , Hidmi Taghreed , Pomyalov Sergei , Lansky Shifra , Khouri Lareen , Shalev Deborah E. , Shoham Gil , Metanis Norman
Published: March 2021

The in vitro oxidative folding of proteins has been studied for over sixty years, providing critical insight into protein folding mechanisms. Hirudin, the most potent natural inhibitor of thrombin, is a 65-residue protein with three disulfide bonds, and is viewed as a folding model for a wide range of disulfide-rich proteins. Hirudin’s folding pathway is notorious for its highly heterogeneous intermediates and scrambled isomers, limiting its folding rate and yield in vitro. Aiming to overcome these limitations, we undertake systematic investigation of diselenide bridges at native and non-native positions and investigate their effect on hirudin’s folding, structure and activity. Our studies demonstrate that, regardless of the specific positions of these substitutions, the diselenide crosslinks enhanced the folding rate and yield of the corresponding hirudin analogues, while reducing the complexity and heterogeneity of the process. Moreover, crystal structure analysis confirms that the diselenide substitutions maintained the overall three-dimensional structure of the protein and left its function virtually unchanged. The choice of hirudin as a study model has implications beyond its specific folding mechanism, demonstrating the high potential of diselenide substitutions in the design, preparation and characterization of disulfide-rich proteins.
Dynamic chiral self-recognition in aromatic dimers of styrene oxide revealed by rotational spectroscopy
Authors: Domingos Sérgio R. , Pérez Cristóbal , Kreienborg Nora M. , Merten Christian , Schnell Melanie
Published: March 2021

Chiral molecular recognition is a pivotal phenomenon in biomolecular science, governed by subtle balances of intermolecular forces that are difficult to quantify. Non-covalent interactions involving aromatic moieties are particularly important in this realm, as recurring motifs in biomolecular aggregation. In this work, we use high-resolution broadband rotational spectroscopy to probe the dynamic conformational landscape enclosing the self-pairing topologies of styrene oxide, a chiral aromatic system. We reach a definite assignment of four homochiral and two heterochiral dimers using auxiliary quantum chemistry calculations as well as structure-solving methods based on experimental isotopic information. A complete picture of the dimer conformational space is obtained, and plausible routes for conformational relaxation are derived. Molecular structures are discussed in terms of conformational flexibility, the concerted effort of weak intermolecular interactions, and their role in the expression of the molecular fit.
Spin-states in MoS2 thin-film transistors distinguished by operando electron spin resonance
Authors: Tsunetomo Naho , Iguchi Shohei , Wierzbowska Małgorzata , Ueda Akiko , Won Yousang , Heo Sinae , Jeong Yesul , Wakayama Yutaka , Marumoto Kazuhiro
Published: March 2021

Transition metal dichalcogenide MoS2 is a two-dimensional material, attracting much attention for next-generation applications thanks to rich functionalities stemming from its crystal structure. Many experimental and theoretical works have focused on the spin-orbit interaction which couples the valley and spin degrees of freedom so that the spin-states can be electrically controllable. However, the spin-states of charge carriers and atomic vacancies in devices have not been yet elucidated directly from a microscopic viewpoint. Here, we report the spin-states in thin-film transistors using operando electron spin resonance spectroscopy. We have observed clearly different electron spin resonance signals of the conduction electrons and atomic vacancies, and distinguished the corresponding spin-states from the signals and theoretical calculations, evaluating the gate-voltage dependence and the spin-susceptibility and g-factor temperature dependence. This analysis gives deep insight into the MoS2 magnetism and clearly indicates different spin-scattering mechanisms compared to graphene, which will be useful for improvements of the device characteristics and new applications.
Supported bilayer membranes for reducing cell adhesion in microfluidic devices
Authors: Clapis Julia R. , Fan Mengqi Jonathan , Kovarik Michelle L.
Published: March 2021

This work characterizes cell adhesion in microchannels coated with supported lipid bilayers of varying charge.
Investigation of vanadium(iii) and vanadium(iv) compounds supported by the linear diaminebis(phenolate) ligands: correlation between structures and magnetic properties
Authors: Janas Zofia , Jezierska Julia , Ozarowski Andrew , Bieńko Alina , Lis Tadeusz , Jezierski Adam , Krawczyk Marta
Published: March 2021

A family of non-oxidovanadium(iii) and oxido-vanadium(iv)-salan compounds has been prepared and characterized by chemical and physical techniques.
The multifaceted dimensions of potent nanostructures: a comprehensive review
Authors: Jamwal Deepika , Sharma Aashima , Kanwar Rohini , Mehta Surinder Kumar
Published: March 2021

Nanoscience as a powerful general-purpose technology for commercialization.
Structure engineering of van der Waals layered transition metal-containing compounds for aqueous energy storage
Authors: Zhou Jinhao , Lu Xihong , Yu Minghao
Published: March 2021

This review summarizes the recently developed structure engineering strategies for layered transition metal-containing compounds in aqueous energy storage applications.