bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the Dietary Approaches to Stop Hypertension (DASH) diet on glycaemic control and consumption of processed and ultraprocessed foods in pregnant women with pre-gestational diabetes mellitus: a randomised clinical trial
Authors: Fagherazzi Sanmira , Farias Dayana Rodrigues , Belfort Gabriella Pinto , dos Santos Karina , Santana Vieira de Lima Thaissa , Silva dos Santos Mayara , Saunders Cláudia
Published: December 2020

The aim of this study was to evaluate the impact of the Dietary Approaches to Stop Hypertension (DASH) diet on glycaemic control and consumption of processed (PF) and ultraprocessed (UPF) foods in pregnant women with pre-gestational diabetes mellitus (PGDM). This is a randomised, controlled, single-blind clinical trial with forty-nine adult women with PGDM, followed at a public maternity hospital in Rio de Janeiro, Brazil. The control group (CG) received a standard diet consisting of 45–55 % of the total energy intake of carbohydrates, 15–20 % of proteins and 25–30 % of lipids. The DASH group (DG) received an adapted DASH diet, which did not differ from the standard diet in the percentage of macronutrients, but had higher contents of fibre, unsaturated fats and minerals such as Ca, Mg and K; and lower contents of Na and saturated fats than the standard diet. In the analysis by protocol, the DG presented a higher incidence of glycaemic control after 12 weeks of intervention (57·1 v. 8·3 %, P = 0·01, moderate effect size) and a lower mean consumption of UPF (−9·9 %, P = 0·01) compared with the CG. There was no statistically significant difference in fasting and postprandial blood glucose concentrations, or in the consumption of PF between the groups (P > 0·05). The DASH diet may be a strategy for glycaemic control in pregnant women with PGDM, favouring the adoption of a nutritionally adequate diet with lower consumption of UPF. Further studies are needed to investigate the effect of the DASH diet on glycaemic profile, and maternal and perinatal outcomes in women with PGDM.
The Politics of Pleasure: Wajid ‘Ali Shah and his manuscript,‘Ishqnama
Authors: DI PIETRANTONIO NATALIA
Published: December 2020

This article deals with an 1849 semi-autobiographical manuscript,‘Ishqnama, from Avadh (present-day Uttar Pradesh), to explore the courtly politics of the last nawab (ruler) of Avadh, Wajid ‘Ali Shah. I argue that, in the‘Ishqnama, a language of love and sex exists and portends a logic of political comportment and control between ruler and lover, ruler and servant. After surveying the importance and meaning of the manuscript during Wajid ‘Ali Shah's reign, I examine the dissemination of the handwritten manuscript via lithograph copies, tracing the specific textual and visual elements that have been obfuscated and manipulated in the transition from a handwritten design to print technology. I argue that the political content of the‘Ishqnamahas been neglected because of the material differences between the lithograph copies and the manuscript format and because of the sexual nature of the‘Ishqnamanarrative.
Is Arctic governance research in crisis? A pathological diagnosis
Authors: Knecht Sebastian , Laubenstein Paula
Published: December 2020

The governance of the Arctic as a frontier for international environmental and climate cooperation, resource politics and security governance holds the promise to provide important insights into some of the 21st century’s most enduring and pressing global challenges. This article reviews the state of the art of Arctic governance research (AGR) to assess the potential and limitations of a regional studies community for making sense of Northern politics and contributing to the broader discipline of international relations (IR) research. A bibliometric analysis of 398 articles published in 10 outlets between 2008 and 2019 reveals that AGR faces at least four limitations that undermine understanding and explaining the processes and outcomes of regional politics and inhibit generalisable observations applicable to questions of global governance: academic immaturity, methodological monoculturalism, state-centrism and analytical parochialism. The lack particularly of theoretically driven and comparative research is indicative of a deeper crisis in AGR which, if unaddressed, could further solidify the community’s unjustified reputation as quixotic in orientation and negligible in its contributions to IR research.
Application of colour combinations on visual search tasks under vibration environments
Authors: Wang Hailiang , Tao Da , Liu Shuang , Zhou Tuoyang , Qu Xingda
Published: December 2020

Colour is widely utilised as a visual coding system in visual search, but its application under vibration conditions (e.g., in various vehicles) has not been fully explored. This study was designed to examine the effect of colour combinations on performance of visual search tasks conducted in vibration conditions. Forty-eight university students participated in an experiment where they were required to identify target type and location under 24 colour combinations (half in negative polarity and half in positive polarity) and three vibration conditions (static, low, and high). The findings showed that vibration did not significantly affect performance, perceptions, or physiological aspects. Colour combination significantly affected response time, and the participants preferred colour combinations that had the potential to produce better performance. Colour combinations with negative polarity (e.g., yellow on black and white on black) are recommended for presenting search interfaces. These findings are of importance in human–computer interface designs for information display under vibration conditions.
A neural network model for solvency calculations in life insurance
Authors: Fernandez-Arjona Lucio
Published: December 2020

Insurance companies make extensive use of Monte Carlo simulations in their capital and solvency models. To overcome the computational problems associated with Monte Carlo simulations, most large life insurance companies use proxy models such as replicating portfolios (RPs). In this paper, we present an example based on a variable annuity guarantee, showing the main challenges faced by practitioners in the construction of RPs: the feature engineering step and subsequent basis function selection problem. We describe how neural networks can be used as a proxy model and how to apply risk-neutral pricing on a neural network to integrate such a model into a market risk framework. The proposed model naturally solves the feature engineering and feature selection problems of RPs.
Improvement of Drag Coefficient Calculation Under Near‐Neutral Conditions in Light Winds Over land
Authors: Liu Changwei , Li Yubin , Gao Zhiqiu , Zhang Hongsheng , Wu Tongwen , Lu Yixiong , Zhang Xiaoye
Published: December 2020

By analyzing the data collected over a rice paddy field in China, the occurrence of large drag coefficient in light winds (U ≤ 1ms−1) under near‐neutral conditions (−0.1 ≤ z/L ≤ 0.1) is analyzed in this study. It is found that, with the use of either vector‐ or scalar‐averaged wind speed, the drag coefficient under near‐neutral conditions (CDN) always increases with the decrease of wind speed. Such behavior of CDN cannot be interpreted by the change of aerodynamic roughness length z0 because it would need to be enlarged by an order of magnitude. While in light winds, the nonlocal transport, which is caused by large‐scale eddies and overlooked by traditional Monin‐Obukhov Similarity theory, is found to be the main cause of increased CDN. At last, a fixing term related to nonlocal effects is proposed based on our observation, and its applicability is verified with two AmeriFlux observation sites with a landscape of forest and savanna, respectively.
Strong Influence of Changes in Terrestrial Water Storage on Flood Potential in India
Authors: Shah Deep , Mishra Vimal
Published: December 2020

Rapid groundwater depletion due to anthropogenic pumping for irrigation poses enormous challenges on socio‐economic, agricultural, and financial spheres of India. However, the role of groundwater depletion on flood potential in India remains unexplored. We examine the role of changes in terrestrial water and groundwater storage on flood potential using in situ and Gravity Recovery and Climate Experiment (GRACE) satellites observations and the simulations from the Variable Infiltration Capacity (VIC) model. Terrestrial Water Storage (TWS) has declined significantly (p value <0.05) with a rate of −0.63 cm yr−1 during 2002–2016 in the Indian subcontinent. Ganga, Brahmaputra, Indus, Brahmani, and Subernarekha river basins experienced a significant decline while Godavari, Mahi, Tapi, and Narmada basins witnessed a substantial increase in TWS during 2002–2016. The relative contribution of TWS on flood potential is higher than precipitation for the majority of the subcontinental river basins. The significant increase/decline in TWS in the subcontinental river basins is driven by the changes in groundwater storage either due to groundwater pumping or natural variability in climate. A significant decrease (increase) in the flood potential in Ganga, Brahmaputra, and Indus (Godavari, Narmada, and Tapi) is linked to the changes in groundwater storage, which shows the influence of groundwater storage variability beyond water and food security in the region.
Aerosol‐Radiation Interactions of Dust Storm Deteriorate Particle and Ozone Pollution in East China
Authors: Wang Zilin , Huang Xin , Wang Nan , Xu Jiawei , Ding Aijun
Published: December 2020

East Asia features frequent dust storms and intensive anthropogenic emissions. The mixing of natural dust and anthropogenic pollutants exerts complicated impacts on air pollution and regional climate. Studies have focused on chemical interactions of the mixed pollution, while the meteorological feedback and influences on atmospheric chemistry have not been fully investigated. Here, a comprehensive study on a widespread dust storm and its influence on the air quality downwind was conducted by combining multiple observations and modeling. We found that dust originated from Gobi Desert was mixed with anthropogenic pollutants after transported to the Yangtze River Delta (YRD). Through scattering and absorbing radiation, dust aerosol perturbed solar energy budget and led to a more stabilized planetary boundary layer (PBL). A reduction of 15% in PBL height (184 m) weakened the dispersion of locally emitted pollutants and increased primary pollution by 10% in YRD city clusters. Besides, the mixed plume over offshore areas warmed the entire lower atmosphere and increased surface evaporation. Accordingly, ozone formation was accelerated by ∼1 ppbv/h within PBL under higher temperature, and secondary aerosol was increased due to faster photochemical and heterogeneous oxidation. Such enhancements substantially contributed to air quality deterioration in YRD region. This work reveals the complexity of interactions between natural dust and anthropogenic pollutants through both atmospheric chemistry and meteorological feedbacks, which is of great importance in both regional air pollution and climate.
Metagenomic analysis reveals a dynamic microbiome with diversified adaptive functions to utilize high lignocellulosic forages in the cattle rumen
Authors: Gharechahi Javad , Vahidi Mohammad Farhad , Bahram Mohammad , Han Jian-Lin , Ding Xue-Zhi , Salekdeh Ghasem Hosseini
Published: December 2020

Rumen microbiota play a key role in the digestion and utilization of plant materials by the ruminant species, which have important implications for greenhouse gas emission. Yet, little is known about the key taxa and potential gene functions involved in the digestion process. Here, we performed a genome-centric analysis of rumen microbiota attached to six different lignocellulosic biomasses in rumen-fistulated cattle. Our metagenome sequencing provided novel genomic insights into functional potential of 523 uncultured bacteria and 15 mostly uncultured archaea in the rumen. The assembled genomes belonged mainly to Bacteroidota, Firmicutes, Verrucomicrobiota, and Fibrobacterota and were enriched for genes related to the degradation of lignocellulosic polymers and the fermentation of degraded products into short chain volatile fatty acids. We also found a shift from copiotrophic to oligotrophic taxa during the course of rumen fermentation, potentially important for the digestion of recalcitrant lignocellulosic substrates in the physiochemically complex and varying environment of the rumen. Differential colonization of forages (the incubated lignocellulosic materials) by rumen microbiota suggests that taxonomic and metabolic diversification is an evolutionary adaptation to diverse lignocellulosic substrates constituting a major component of the cattle’s diet. Our data also provide novel insights into the key role of unique microbial diversity and associated gene functions in the degradation of recalcitrant lignocellulosic materials in the rumen.
Inhibition of EZH2 ameliorates bacteria-induced liver injury by repressing RUNX1 in dendritic cells
Authors: Wang Yanan , Wang Qiwei , Wang Bei , Gu Yuting , Yu Hongshuang , Yang Wanlin , Ren Xiaohui , Qian Fengtao , Zhao Xiaonan , Xiao Yichuan , Zhang Yanyun , Jin Min , Zhu Meiling
Published: December 2020

Fulminant hepatic failure (FHF) is a clinical syndrome characterized by a sudden and severe impairment in liver function. However, the precise mechanism of immune dysregulation that is significant to FHF pathogenesis remains unclear. Enhancer of zeste homolog 2 (EZH2) has been implicated in inflammation as a regulator of immune cell function. In this study, we investigated the role of EZH2 in an animal model of human FHF induced byPropionibacterium acnes(P. acnes) and lipopolysaccharide (LPS). We demonstrated that EZH2 depletion in dendritic cells (DCs) and pharmacological inhibition of EZH2 using GSK126 both significantly ameliorated liver injury and improved the survival rates of mice withP. acnesplus LPS-induced FHF, which could be attributed to the decreased infiltration and activation of CD4+T cells in the liver, inhibition of T helper 1 cells and induction of regulatory T cells. The expression of EZH2 in DCs was increased afterP. acnesadministration, and EZH2 deficiency in DCs suppressed DC maturation and prevented DCs from efficiently stimulating CD4+T-cell proliferation. Further mechanistic analyses indicated that EZH2 deficiency directly increased the expression of the transcription factor RUNX1 and thereby suppressed the immune functions of DCs. The functional dependence of EZH2 on RUNX1 was further illustrated in DC-specificEzh2-deficient mice. Taken together, our findings establish that EZH2 exhibits anti-inflammatory effects through inhibition of RUNX1 to regulate DC functions and that inhibition of EZH2 alleviatesP. acnesplus LPS-induced FHF, probably by inhibiting DC-induced adaptive immune responses. These results highlight the effect of EZH2 on DCs, serving as a guide for the development of a promising immunotherapeutic strategy for FHF.
The carrot monoterpene synthase gene cluster on chromosome 4 harbours genes encoding flavour-associated sabinene synthases
Authors: Reichardt Sven , Budahn Holger , Lamprecht Dominic , Riewe David , Ulrich Detlef , Dunemann Frank , Kopertekh Lilya
Published: December 2020

In plants, low molecular weight terpenes produced by terpene synthases (TPS) contribute to multiple ecologically and economically important traits. The present study investigates a carrot terpene synthase gene cluster on chromosome 4 associated with volatile monoterpene production. Two carrot mutants,yellowandcola, which are contrasting in the content of low molecular weight terpenes, were crossed to develop an F2mapping population. The mapping analysis revealed overlapping QTLs on chromosome 4 for sabinene, α-thujene, α-terpinene, γ-terpinene, terpinen-4-ol and 4-carene. The genomic region of this locus includes a cluster of five terpene synthase genes (DcTPS04,DcTPS26, DcTPS27, DcTPS54andDcTPS55).DcTPS04andDcTPS54displayed genotype- and tissue-specific variation in gene expression. Based on the QTL mapping results and the gene expression patterns,DcTPS04andDcTPS54were selected for functional characterization. In vitro enzyme assays showed thatDcTPS54 is a single-product enzyme catalysing the formation of sabinene, whereasDcTPS04 is a multiple-product terpene synthase producing α-terpineol as a major product and four additional products including sabinene, β-limonene, β-pinene and myrcene. Furthermore, we developed a functional molecular marker that could discriminate carrot genotypes with different sabinene content in a set of 85 accessions.
A chromosome-scale genome assembly of a diploid alfalfa, the progenitor of autotetraploid alfalfa
Authors: Li Ao , Liu Ai , Du Xin , Chen Jin-Yuan , Yin Mou , Hu Hong-Yin , Shrestha Nawal , Wu Sheng-Dan , Wang Hai-Qing , Dou Quan-Wen , Liu Zhi-Peng , Liu Jian-Quan , Yang Yong-Zhi , Ren Guang-Peng
Published: December 2020

Alfalfa (Medicago sativa L.) is one of the most important and widely cultivated forage crops. It is commonly used as a vegetable and medicinal herb because of its excellent nutritional quality and significant economic value. Based on Illumina, Nanopore and Hi-C data, we assembled a chromosome-scale assembly of Medicago sativa spp. caerulea (voucher PI464715), the direct diploid progenitor of autotetraploid alfalfa. The assembled genome comprises 793.2 Mb of genomic sequence and 47,202 annotated protein-coding genes. The contig N50 length is 3.86 Mb. This genome is almost twofold larger and contains more annotated protein-coding genes than that of its close relative, Medicago truncatula (420 Mb and 44,623 genes). The more expanded gene families compared with those in M. truncatula and the expansion of repetitive elements rather than whole-genome duplication (i.e., the two species share the ancestral Papilionoideae whole-genome duplication event) may have contributed to the large genome size of M. sativa spp. caerulea. Comparative and evolutionary analyses revealed that M. sativa spp. caerulea diverged from M. truncatula ~5.2 million years ago, and the chromosomal fissions and fusions detected between the two genomes occurred during the divergence of the two species. In addition, we identified 489 resistance (R) genes and 82 and 85 candidate genes involved in the lignin and cellulose biosynthesis pathways, respectively. The near-complete and accurate diploid alfalfa reference genome obtained herein serves as an important complement to the recently assembled autotetraploid alfalfa genome and will provide valuable genomic resources for investigating the genomic architecture of autotetraploid alfalfa as well as for improving breeding strategies in alfalfa.
Multiomics analyses unveil the involvement of microRNAs in pear fruit senescence under high- or low-temperature conditions
Authors: Gu Chao , Xu Huan-Yu , Zhou Yu-Hang , Yao Jia-Long , Xie Zhi-Hua , Chen Yang-Yang , Zhang Shao-Ling
Published: December 2020

Senescence leads to declines in fruit quality and shortening of shelf life. It is known that low temperatures (LTs) efficiently delay fruit senescence and that high temperatures (HTs) accelerate senescence. However, the molecular mechanism by which temperature affects senescence is unclear. Herein, through multiomics analyses of fruits subjected to postharvest HT, LT, and room temperature treatments, a total of 56 metabolic compounds and 700 mRNAs were identified to be associated with fruit senescence under HT or LT conditions. These compounds could be divided into antisenescent (I→III) and prosenescent (IV→VI) types. HT affected the expression of 202 mRNAs to enhance the biosynthesis of prosenescent compounds of types V and VI and to inhibit the accumulation of antisenescent compounds of types II and III. LT affected the expression of 530 mRNAs to promote the accumulation of antisenescent compounds of types I and II and to impede the biosynthesis of prosenescent compounds of types IV and V. Moreover, 16 microRNAs were isolated in response to HT or LT conditions and interacted with the mRNAs associated with fruit senescence under HT or LT conditions. Transient transformation of pear fruit showed that one of these microRNAs, Novel_188, can mediate fruit senescence by interacting with its target Pbr027651.1. Thus, both HT and LT conditions can affect fruit senescence by affecting microRNA–mRNA interactions, but the molecular networks are different in pear fruit.
Integrated transcriptome and proteome analysis provides insight into chilling-induced dormancy breaking in Chimonanthus praecox
Authors: Li Zhineng , Liu Ning , Zhang Wei , Wu Chunyu , Jiang Yingjie , Ma Jing , Li Mingyang , Sui Shunzhao
Published: December 2020

Chilling has a critical role in the growth and development of perennial plants. The chilling requirement (CR) for dormancy breaking largely depends on the species. However, global warming is expected to negatively affect chilling accumulation and dormancy release in a wide range of perennial plants. Here, we usedChimonanthus praecoxas a model to investigate the CR for dormancy breaking under natural and artificial conditions. We determined the minimum CR (570 chill units, CU) needed for chilling-induced dormancy breaking and analyzed the transcriptomes and proteomes of flowering and non-flowering flower buds (FBs, anther and ovary differentiation completed) with different CRs. The concentrations of ABA and GA3 in the FBs were also determined using HPLC. The results indicate that chilling induced an upregulation of ABA levels and significant downregulation ofSHORT VEGETATIVE PHASE(SVP) andFLOWERING LOCUS T(FT) homologs at the transcript level in FBs when the accumulated CR reached 570 CU (IB570) compared to FBs in November (FB.Nov, CK) and nF16 (non-flowering FBs after treatment at 16 °C for −300 CU), which suggested that dormancy breaking of FBs could be regulated by the ABA-mediated SVP-FT module. Overexpression inArabidopsiswas used to confirm the function of candidate genes, and early flowering was induced in35S::CpFT1transgenic lines. Our data provide insight into the minimum CR (570 CU) needed for chilling-induced dormancy breaking and its underlying regulatory mechanism inC. praecox, which provides a new tool for the artificial regulation of flowering time and a rich gene resource for controlling chilling-induced blooming.
Genome sequencing and phylogenetic analysis of allotetraploid Salix matsudana Koidz
Authors: Zhang Jian , Yuan Huwei , Li Yujuan , Chen Yanhong , Liu Guoyuan , Ye Meixia , Yu Chunmei , Lian Bolin , Zhong Fei , Jiang Yuna , Xu Jichen
Published: December 2020

Polyploidy is a common phenomenon among willow species. In this study, genome sequencing was conducted for Salix matsudana Koidz (also named Chinese willow), an important greening and arbor tree species, and the genome of this species was compared with those of four other tree species in Salicaceae. The total genome sequence of S. matsudana was 655.72 Mb in size, with repeated sequences accounting for 45.97% of the total length. In total, 531.43 Mb of the genome sequence could be mapped onto 38 chromosomes using the published genetic map as a reference. The genome of S. matsudana could be divided into two groups, the A and B genomes, through homology analysis with the genome of Populus trichocarpa, and the A and B genomes contained 23,985 and 25,107 genes, respectively. 4DTv combined transposon analysis predicted that allotetraploidy in S. matsudana appeared ~4 million years ago. The results from this study will help reveal the evolutionary history of S. matsudana and lay a genetic basis for its breeding.
A macrophage-specific lncRNA regulates apoptosis and atherosclerosis by tethering HuR in the nucleus
Authors: Simion Viorel , Zhou Haoyang , Haemmig Stefan , Pierce Jacob B. , Mendes Shanelle , Tesmenitsky Yevgenia , Pérez-Cremades Daniel , Lee James F. , Chen Alex F. , Ronda Nicoletta , Papotti Bianca , Marto Jarrod A. , Feinberg Mark W.
Published: December 2020

Long non-coding RNAs (lncRNAs) are emerging regulators of pathophysiological processes including atherosclerosis. Using RNA-seq profiling of the intima of lesions, here we identify a macrophage-specific lncRNA MAARS (Macrophage-Associated Atherosclerosis lncRNA Sequence). Aortic intima expression of MAARS increases by 270-fold with atherosclerotic progression and decreases with regression by 60%. MAARS knockdown reduces atherosclerotic lesion formation by 52% in LDLR−/− mice, largely independent of effects on lipid profile and inflammation, but rather by decreasing macrophage apoptosis and increasing efferocytosis in the vessel wall. MAARS interacts with HuR/ELAVL1, an RNA-binding protein and important regulator of apoptosis. Overexpression and knockdown studies verified MAARS as a critical regulator of macrophage apoptosis and efferocytosis in vitro, in an HuR-dependent manner. Mechanistically, MAARS knockdown alters HuR cytosolic shuttling, regulating HuR targets such as p53, p27, Caspase-9, and BCL2. These findings establish a mechanism by which a macrophage-specific lncRNA interacting with HuR regulates apoptosis, with implications for a broad range of vascular disease states.
Non-invasive focusing and imaging in scattering media with a fluorescence-based transmission matrix
Authors: Boniface Antoine , Dong Jonathan , Gigan Sylvain
Published: December 2020

In biological microscopy, light scattering represents the main limitation to image at depth. Recently, a set of wavefront shaping techniques has been developed in order to manipulate coherent light in strongly disordered materials. The Transmission Matrix approach has shown its capability to inverse the effect of scattering and efficiently focus light. In practice, the matrix is usually measured using an invasive detector or low-resolution acoustic guide stars. Here, we introduce a non-invasive and all-optical strategy based on linear fluorescence to reconstruct the transmission matrices, to and from a fluorescent object placed inside a scattering medium. It consists in demixing the incoherent patterns emitted by the object using low-rank factorizations and phase retrieval algorithms. We experimentally demonstrate the efficiency of this method through robust and selective focusing. Additionally, from the same measurements, it is possible to exploit memory effect correlations to image and reconstruct extended objects. This approach opens up a new route towards imaging in scattering media with linear or non-linear contrast mechanisms.
Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase
Authors: Siedner Mark J. , Moorhouse Michelle A. , Simmons Bryony , de Oliveira Tulio , Lessells Richard , Giandhari Jennifer , Kemp Stephen A. , Chimukangara Benjamin , Akpomiemie Godspower , Serenata Celicia M. , Venter Willem D. F. , Hill Andrew , Gupta Ravindra K.
Published: December 2020

Little is known about the impact of pretreatment drug resistance (PDR) on the efficacy of second generation integrase inhibitors. We sequenced pretreatment plasma specimens from the ADVANCE trial (NCT03122262). Our primary outcome was 96-week virologic success, defined as a sustained viral load <1000 copies/mL from 12 weeks onwards, <200 copies/mL from 24 weeks onwards, and <50 copies/mL after 48 weeks. Here we report how this outcome was impacted by PDR, defined by the World Health Organization (WHO) mutation list. Of 1053 trial participants, 874 (83%) have successful sequencing, including 289 (33%) randomized to EFV-based therapy and 585 (67%) randomized to DTG-based therapy. Fourteen percent (122/874) have ≥1 WHO-defined mutation, of which 98% (120/122) are NNRTI mutations. Rates of virologic suppression are lower in the total cohort among those with PDR 65% (73/112) compared to those without PDR (85% [605/713], P < 0.001), and for those on EFV-based treatment (60% [12/20] vs 86% [214/248], P = 0.002) and for those on DTG-based treatment (61/92 [66%] vs 84% [391/465] P < 0.001, P for interaction by regimen 0.49). Results are similar in multivariable models adjusted for clinical characteristics and adherence. NNRTI resistance prior to treatment is associated with long-term failure of integrase inhibitor-containing first-line regimens, and portends high rates of first-line failure in sub Saharan Africa.
Quantitative modeling predicts mechanistic links between pre-treatment microbiome composition and metronidazole efficacy in bacterial vaginosis
Authors: Lee Christina Y. , Cheu Ryan K. , Lemke Melissa M. , Gustin Andrew T. , France Michael T. , Hampel Benjamin , Thurman Andrea R. , Doncel Gustavo F. , Ravel Jacques , Klatt Nichole R. , Arnold Kelly B.
Published: December 2020

Bacterial vaginosis is a condition associated with adverse reproductive outcomes and characterized by a shift from a Lactobacillus-dominant vaginal microbiota to a polymicrobial microbiota, consistently colonized by strains of Gardnerella vaginalis. Metronidazole is the first-line treatment; however, treatment failure and recurrence rates remain high. To understand complex interactions between Gardnerella vaginalis and Lactobacillus involved in efficacy, here we develop an ordinary differential equation model that predicts bacterial growth as a function of metronidazole uptake, sensitivity, and metabolism. The model shows that a critical factor in efficacy is Lactobacillus sequestration of metronidazole, and efficacy decreases when the relative abundance of Lactobacillus is higher pre-treatment. We validate results in Gardnerella and Lactobacillus co-cultures, and in two clinical cohorts, finding women with recurrence have significantly higher pre-treatment levels of Lactobacillus relative to bacterial vaginosis–associated bacteria. Overall results provide mechanistic insight into how personalized differences in microbial communities influence vaginal antibiotic efficacy.
Functionally impaired plasmacytoid dendritic cells and non-haematopoietic sources of type I interferon characterize human autoimmunity
Authors: Psarras Antonios , Alase Adewonuola , Antanaviciute Agne , Carr Ian M. , Md Yusof Md Yuzaiful , Wittmann Miriam , Emery Paul , Tsokos George C. , Vital Edward M.
Published: December 2020

Autoimmune connective tissue diseases arise in a stepwise fashion from asymptomatic preclinical autoimmunity. Type I interferons have a crucial role in the progression to established autoimmune diseases. The cellular source and regulation in disease initiation of these cytokines is not clear, but plasmacytoid dendritic cells have been thought to contribute to excessive type I interferon production. Here, we show that in preclinical autoimmunity and established systemic lupus erythematosus, plasmacytoid dendritic cells are not effector cells, have lost capacity for Toll-like-receptor-mediated cytokine production and do not induce T cell activation, independent of disease activity and the blood interferon signature. In addition, plasmacytoid dendritic cells have a transcriptional signature indicative of cellular stress and senescence accompanied by increased telomere erosion. In preclinical autoimmunity, we show a marked enrichment of an interferon signature in the skin without infiltrating immune cells, but with interferon-κ production by keratinocytes. In conclusion, non-hematopoietic cellular sources, rather than plasmacytoid dendritic cells, are responsible for interferon production prior to clinical autoimmunity.
Deep learning suggests that gene expression is encoded in all parts of a co-evolving interacting gene regulatory structure
Authors: Zrimec Jan , Börlin Christoph S. , Buric Filip , Muhammad Azam Sheikh , Chen Rhongzen , Siewers Verena , Verendel Vilhelm , Nielsen Jens , Töpel Mats , Zelezniak Aleksej
Published: December 2020

Understanding the genetic regulatory code governing gene expression is an important challenge in molecular biology. However, how individual coding and non-coding regions of the gene regulatory structure interact and contribute to mRNA expression levels remains unclear. Here we apply deep learning on over 20,000 mRNA datasets to examine the genetic regulatory code controlling mRNA abundance in 7 model organisms ranging from bacteria to Human. In all organisms, we can predict mRNA abundance directly from DNA sequence, with up to 82% of the variation of transcript levels encoded in the gene regulatory structure. By searching for DNA regulatory motifs across the gene regulatory structure, we discover that motif interactions could explain the whole dynamic range of mRNA levels. Co-evolution across coding and non-coding regions suggests that it is not single motifs or regions, but the entire gene regulatory structure and specific combination of regulatory elements that define gene expression levels.
Conformational maps of human 20S proteasomes reveal PA28- and immuno-dependent inter-ring crosstalks
Authors: Lesne Jean , Locard-Paulet Marie , Parra Julien , Zivković Dušan , Menneteau Thomas , Bousquet Marie-Pierre , Burlet-Schiltz Odile , Marcoux Julien
Published: December 2020

Hydrogen-Deuterium eXchange coupled to Mass Spectrometry (HDX-MS) is now common practice in structural biology. However, it is most of the time applied to rather small oligomeric complexes. Here, we report on the use of HDX-MS to investigate conformational differences between the human standard 20S (std20S) and immuno 20S (i20s) proteasomes alone or in complex with PA28αβ or PA28γ activators. Their solvent accessibility is analyzed through a dedicated bioinformatic pipeline including stringent statistical analysis and 3D visualization. These data confirm the existence of allosteric differences between the std20S and i20S at the surface of the α-ring triggered from inside the catalytic β-ring. Additionally, binding of the PA28 regulators to the 20S proteasomes modify solvent accessibility due to conformational changes of the β-rings. This work is not only a proof-of-concept that HDX-MS can be used to get structural insights on large multi-protein complexes in solution, it also demonstrates that the binding of the std20S or i20S subtype to any of its PA28 activator triggers allosteric changes that are specific to this 20S/PA28 pair.
Hippocampal adult-born granule cells drive network activity in a mouse model of chronic temporal lobe epilepsy
Authors: Sparks F. T. , Liao Z. , Li W. , Grosmark A. , Soltesz I. , Losonczy A.
Published: December 2020

Temporal lobe epilepsy (TLE) is characterized by recurrent seizures driven by synchronous neuronal activity. The reorganization of the dentate gyrus (DG) in TLE may create pathological conduction pathways for synchronous discharges in the temporal lobe, though critical microcircuit-level detail is missing from this pathophysiological intuition. In particular, the relative contribution of adult-born (abGC) and mature (mGC) granule cells to epileptiform network events remains unknown. We assess dynamics of abGCs and mGCs during interictal epileptiform discharges (IEDs) in mice with TLE as well as sharp-wave ripples (SPW-Rs) in healthy mice, and find that abGCs and mGCs are desynchronized and differentially recruited by IEDs compared to SPW-Rs. We introduce a neural topic model to explain these observations, and find that epileptic DG networks organize into disjoint, cell-type specific pathological ensembles in which abGCs play an outsized role. Our results characterize identified GC subpopulation dynamics in TLE, and reveal a specific contribution of abGCs to IEDs.
The liverwort oil body is formed by redirection of the secretory pathway
Authors: Kanazawa Takehiko , Morinaka Hatsune , Ebine Kazuo , Shimada Takashi L. , Ishida Sakiko , Minamino Naoki , Yamaguchi Katsushi , Shigenobu Shuji , Kohchi Takayuki , Nakano Akihiko , Ueda Takashi
Published: December 2020

Eukaryotic cells acquired novel organelles during evolution through mechanisms that remain largely obscure. The existence of the unique oil body compartment is a synapomorphy of liverworts that represents lineage-specific acquisition of this organelle during evolution, although its origin, biogenesis, and physiological function are yet unknown. We find that two paralogous syntaxin-1 homologs in the liverwort Marchantia polymorpha are distinctly targeted to forming cell plates and the oil body, suggesting that these structures share some developmental similarity. Oil body formation is regulated by an ERF/AP2-type transcription factor and loss of the oil body increases M. polymorpha herbivory. These findings highlight a common strategy for the acquisition of organelles with distinct functions in plants, via periodical redirection of the secretory pathway depending on cellular phase transition.
Bioinformatic analysis of membrane and associated proteins in murine cardiomyocytes and human myocardium
Authors: Lee Shin-Haw , Hadipour-Lakmehsari Sina , Kim Da Hye , Di Paola Michelle , Kuzmanov Uros , Shah Saumya , Lee Joseph Jong-Hwan , Kislinger Thomas , Sharma Parveen , Oudit Gavin Y. , Gramolini Anthony O.
Published: December 2020

In the current study we examined several proteomic- and RNA-Seq-based datasets of cardiac-enriched, cell-surface and membrane-associated proteins in human fetal and mouse neonatal ventricular cardiomyocytes. By integrating available microarray and tissue expression profiles with MGI phenotypic analysis, we identified 173 membrane-associated proteins that are cardiac-enriched, conserved amongst eukaryotic species, and have not yet been linked to a ‘cardiac’ Phenotype-Ontology. To highlight the utility of this dataset, we selected several proteins to investigate more carefully, including FAM162A, MCT1, and COX20, to show cardiac enrichment, subcellular distribution and expression patterns in disease. We performed three-dimensional confocal imaging analysis to validate subcellular localization and expression in adult mouse ventricular cardiomyocytes. FAM162A, MCT1, and COX20 were expressed differentially at the transcriptomic and proteomic levels in multiple models of mouse and human heart diseases and may represent potential diagnostic and therapeutic targets for human dilated and ischemic cardiomyopathies. Altogether, we believe this comprehensive cardiomyocyte membrane proteome dataset will prove instrumental to future investigations aimed at characterizing heart disease markers and/or therapeutic targets for heart failure.
Eucalyptus oil reduces allergic reactions and suppresses mast cell degranulation by downregulating IgE-FcεRI signalling
Authors: Nakamura Tomoya , Yoshida Naoki , Yamanoi Yu , Honryo Akira , Tomita Hiroyuki , Kuwabara Hiroki , Kojima Yoshihiko
Published: December 2020

Eucalyptus oil has been used since ancient times for its bactericidal, anti-inflammatory, analgesic and sedative effects. In recent years, the action of Eucalyptus oil has been scientifically proven, and there have been reports that Eucalyptus oil suppresses the production of chemokines, cytokines and lipid mediators in basophils, alveolar macrophages and monocytes. Based on this information, we aimed to verify whether Eucalyptus oil can be used for allergic dermatitis, the incidence of which has been increasing among human skin diseases. This effect was verified using a mouse IgE-mediated local allergic model. In conclusion, topical application of Eucalyptus oil suppressed oedema and vascular permeability enhancement due to IgE-mediated allergic on the skin. In addition, we also verified the degranuration of mast cells, which is a part of its action, and examined whether 1,8-cineole, which is the main component of Eucalyptus oil, suppresses the phosphorylation of PLCγ and p38 directly or indirectly. 1,8-cineole was found to suppress degranulation of mast cells.
Retraction Note: MicroRNA-27a-3p Modulates the Wnt/β-Catenin Signaling Pathway to Promote Epithelial-Mesenchymal Transition in Oral Squamous Carcinoma Stem Cells by Targeting SFRP1
Authors: Qiao Bin , He Bao-Xia , Cai Jing-Hua , Tao Qian , Lam Alfred King-yin
Published: December 2020

Editor's Note: this Article has been retracted; the Retraction Note is available at https://www.nature.com/articles/s41598-020-77203-x
Analysis of recombinant proteins for Q fever diagnostics
Authors: Miller Halie K. , Kersh Gilbert J.
Published: December 2020

Serology is essential for Q fever diagnostics, a disease caused by the bacterial pathogen Coxiella burnetii. The gold standard test is an immunofluorescence assay utilizing whole cell antigens, which are both dangerous and laborious to produce. Complexities of the antigen coupled with the subjective nature of the assay lead to decreased uniformity of test results and underscore the need for improved methodologies. Thirty-three C. burnetii proteins, previously identified as immunoreactive, were screened for reactivity to naturally infected goat serum. Based on reactivity, 10 proteins were analyzed in a secondary screen against human serum from healthy donors. Assay sensitivity and specificity ranged from 21 to 71% and 90 to 100%, respectively. Three promising antigens were identified based on receiver operating characteristic curve analysis (CBU_1718, CBU_0307, and CBU_1398). Five multiplex assays failed to outperform the individual proteins, with sensitivities and specificities ranging from 29 to 57% and 90 to 100%, respectively. Truncating the top antigen, CBU_1718, had no effect on specificity (90%); yet sensitivity decreased dramatically (71% to 21%). Through this study, we have expanded the subset of C. burnetii immunoreactive proteins validated by enzyme-linked immunosorbent assay and demonstrate the effect of novel antigen combinations and protein truncations on assay performance.
Plant growth promotion effect of plasma activated water on Lactuca sativa L. cultivated in two different volumes of substrate
Authors: Stoleru Vasile , Burlica Radu , Mihalache Gabriela , Dirlau Delicia , Padureanu Silvica , Teliban Gabriel-Ciprian , Astanei Dragos , Cojocaru Alexandru , Beniuga Oana , Patras Antoanela
Published: December 2020

Plasma activated water (PAW) can represent an alternative to chemical fertilizers in agriculture. The effects of PAW treatment applied in two concentrations (1.5 or 3.0 mg L−1 NO3−) on some morphological, physiological, biochemical parameters and yield of Lactuca sativa L. grown in two different pot volumes (400 or 3200 cm3) were investigated in this study. The results showed that both PAW concentrations did not influence the germination, once the process was initiated. Positive effects of the treatments were registered on the length of radicle and hypocotyls of lettuce at a concentration of 1.5 mg L−1 NO3− (PAW I), the chlorophyll content was significantly increased at a concentration of 3.0 mg L−1 NO3− (PAW II) and bigger pot volume, also the foliar weight and area. No significant differences between the treated and untreated plants were recorded for the root weight, leaf length and width. The dry weight was significantly higher for the lettuce treated with PAW I and II grown in big volume pots at 57 days after transplanting (DAT) and small volume pots at 64 DAT. The nitrites content of the lettuce grown in big pots was lower than of the lettuce grown in small pots, regardless of the PAW treatment. Contrary, the nitrates content was higher in the lettuce grown in big pots (up to 36.4 mg KNO3/g DW), compared to small pots (under 0.3 mg KNO3/g DW).
Epidemical and etiological study on hand, foot and mouth disease following EV-A71 vaccination in Xiangyang, China
Authors: Meng Xiao-Dan , Tong Yeqing , Wei Zhen-Ni , Wang Lei , Mai Jian-Yi , Wu Yang , Luo Zhi-Yu , Li Shaoping , Li Meng , Wang Siquan , Wei Sheng , Gong Wensheng , Zhang Wangsheng , Hu Xingzhou , Huang Jiao , Shi Jing , Yang Gang , Meng Shengli , Wang Zejun , Guan Xuhua , Shen Shuo
Published: December 2020

Coxsackievirus A6 (CV-A6) and Coxsackievirus A10 (CV-A10) have been emerging as the prevailing serotypes and overtaking Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16) in most areas as main pathogens of hand, foot and mouth disease (HFMD) in China since 2013. To investigate whole etiological spectrum following EV-A71 vaccination of approximate 40,000 infants and young children in Xiangyang, enteroviruses were serotyped in 4415 HFMD cases from October 2016 to December 2017 using Real Time and conventional PCR and cell cultures. Of the typeable 3201 specimen, CV-A6 was the predominant serotype followed by CV-A16, CV-A10, CV-A5, CV-A2 and EV-A71 with proportions of 59.54%, 15.31%, 11.56%, 4.56%, 3.78% and 3.03%, respectively. Other 12 minor serotypes were also detected. The results demonstrated that six major serotypes of enteroviruses were co-circulating, including newly emerged CV-A2 and CV-A5. A dramatic decrease of EV-A71 cases was observed, whereas the total cases remained high. Multivalent vaccines against major serotypes are urgently needed for control of HFMD.
XG-ac4C: identification of N4-acetylcytidine (ac4C) in mRNA using eXtreme gradient boosting with electron-ion interaction pseudopotentials
Authors: Alam Waleed , Tayara Hilal , Chong Kil To
Published: December 2020

N4-acetylcytidine (ac4C) is a post-transcriptional modification in mRNA which plays a major role in the stability and regulation of mRNA translation. The working mechanism of ac4C modification in mRNA is still unclear and traditional laboratory experiments are time-consuming and expensive. Therefore, we propose an XG-ac4C machine learning model based on the eXtreme Gradient Boost classifier for the identification of ac4C sites. The XG-ac4C model uses a combination of electron-ion interaction pseudopotentials and electron-ion interaction pseudopotentials of trinucleotide of the nucleotides in ac4C sites. Moreover, Shapley additive explanations and local interpretable model-agnostic explanations are applied to understand the importance of features and their contribution to the final prediction outcome. The obtained results demonstrate that XG-ac4C outperforms existing state-of-the-art methods. In more detail, the proposed model improves the area under the precision-recall curve by 9.4% and 9.6% in cross-validation and independent tests, respectively. Finally, a user-friendly web server based on the proposed model for ac4C site identification is made freely available athttp://nsclbio.jbnu.ac.kr/tools/xgac4c/.
Harvesting energy from sun, outer space, and soil
Authors: Tian Yanpei , Liu Xiaojie , Chen Fangqi , Zheng Yi
Published: December 2020

While solar power systems have offered a wide variety of electricity generation approaches including photovoltaics, solar thermal power systems, and solar thermoelectric generators, the ability to generate electricity at both the daytime and nighttime with no necessity of energy storage remains challenging. Here, we propose and verify an environment-friendly, sustainable, and cost-effective strategy of harvesting solar energy by solar heating during the daytime and harnessing the coldness of the outer space through radiative cooling to produce electricity at night using a commercial thermoelectric module. It enables electricity generation for 24 h a day. We experimentally demonstrate a peak power density of 37 mW/m$$^2$$

2

at night and a peak value of 723 mW/m$$^2$$

2

during the daytime. A theoretical model that accurately predicts the performance of the device is developed and validated. The feature of 24-h electricity generation shows great potential energy applications of off-grid and battery-free lighting and sensing.