bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-disorder genetic analyses implicate dopaminergic signaling as a biological link between Attention-Deficit/Hyperactivity Disorder and obesity measures
Authors: Mota Nina Roth , Poelmans Geert , Klein Marieke , Torrico Bàrbara , Fernàndez-Castillo Noèlia , Cormand Bru , Reif Andreas , Franke Barbara , Arias Vásquez Alejandro 
Published: January 2020

AbstractAttention-Deficit/Hyperactivity Disorder (ADHD) and obesity are frequently comorbid, genetically correlated, and share brain substrates. The biological mechanisms driving this association are unclear, but candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the genetic link between ADHD and obesity measures and investigate associations of overlapping genes with brain volumes. We tested the association of dopaminergic and circadian rhythm gene sets with ADHD, body mass index (BMI), and obesity (using GWAS data of N = 53,293, N = 681,275, and N = 98,697, respectively). We then conducted genome-wide ADHD–BMI and ADHD–obesity gene-based meta-analyses, followed by pathway enrichment analyses. Finally, we tested the association of ADHD–BMI overlapping genes with brain volumes (primary GWAS data N = 10,720–10,928; replication data N = 9428). The dopaminergic gene set was associated with both ADHD (P = 5.81 × 10−3) and BMI (P = 1.63 × 10−5); the circadian rhythm was associated with BMI (P = 1.28 × 10−3). The genome-wide approach also implicated the dopaminergic system, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was enriched in both ADHD–BMI and ADHD–obesity results. The ADHD–BMI overlapping genes were associated with putamen volume (P = 7.7 × 10−3; replication data P = 3.9 × 10−2)—a brain region with volumetric reductions in ADHD and BMI and linked to inhibitory control. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling and involving the putamen, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering shared etiological factors underlying the frequently observed ADHD–obesity comorbidity may have important implications in terms of prevention and/or efficient treatment of these conditions.
Novel syntrophic bacteria in full-scale anaerobic digesters revealed by genome-centric metatranscriptomics
Authors: Hao Liping , Michaelsen Thomas Yssing , Singleton Caitlin Margaret , Dottorini Giulia , Kirkegaard Rasmus Hansen , Albertsen Mads , Nielsen Per Halkjær , Dueholm Morten Simonsen 
Published: January 2020

Abstract
Short-chain fatty acid (SCFA) degradation is an important process in methanogenic ecosystems, and is usually catalyzed by SCFA-oxidizing bacteria in syntrophy with methanogens. Current knowledge of this functional guild is mainly based on isolates or enrichment cultures, but these may not reflect the true diversity and in situ activities of the syntrophs predominating in full-scale systems. Here we obtained 182 medium to high quality metagenome-assembled genomes (MAGs) from the microbiome of two full-scale anaerobic digesters. The transcriptomic response of individual MAG was studied after stimulation with low concentrations of acetate, propionate, or butyrate, separately. The most pronounced response to butyrate was observed for two MAGs of the recently described genus Candidatus Phosphitivorax (phylum Desulfobacterota), expressing a butyrate beta-oxidation pathway. For propionate, the largest response was observed for an MAG of a novel genus in the family Pelotomaculaceae, transcribing a methylmalonyl-CoA pathway. All three species were common in anaerobic digesters at Danish wastewater treatment plants as shown by amplicon analysis, and this is the first time their syntrophic features involved in SCFA oxidation were revealed with transcriptomic evidence. Further, they also possessed unique genomic features undescribed in well-characterized syntrophs, including the metabolic pathways for phosphite oxidation, nitrite and sulfate reduction.
Mycobacterium bovis uses the ESX-1 Type VII secretion system to escape predation by the soil-dwelling amoeba Dictyostelium discoideum
Authors: Butler Rachel E , Smith Alex A , Mendum Tom A , Chandran Aneesh , Wu Huihai , Lefrançois Louise , Chambers Mark , Soldati Thierry , Stewart Graham R 
Published: January 2020

Abstract
Mycobacterium bovis is the causative agent of bovine tuberculosis and the predominant cause of zoonotic tuberculosis in people. Bovine tuberculosis occurs in farmed cattle but also in a variety of wild animals, which form a reservoir of infection. Although direct transmission of tuberculosis occurs between mammals, the low frequency of contact between different host species and abundant shedding of bacilli by infected animals suggests an infectious route via environmental contamination. Other intracellular pathogens that transmit via the environment deploy strategies to survive or exploit predation by environmental amoebae. To explore if M. bovis has this capability, we investigated its interactions with the soil and dung-dwelling amoeba, Dictyostelium discoideum. We demonstrated that M. bovis evades phagocytosis and destruction by D. discoideum and actively transits through the amoeba using the ESX-1 Type VII Secretion System as part of a programme of mechanisms, many of which have been co-opted as virulence factors in the mammalian host. This capacity of M. bovis to utilise an environmental stage between mammalian hosts may enhance its transmissibility. In addition, our data provide molecular evidence to support an evolutionary role for amoebae as training grounds for the pathogenic M. tuberculosis complex.
Organohalide-respiring Desulfoluna species isolated from marine environments
Authors: Peng Peng , Goris Tobias , Lu Yue , Nijsse Bart , Burrichter Anna , Schleheck David , Koehorst Jasper J , Liu Jie , Sipkema Detmer , Sinninghe Damste Jaap S , Stams Alfons J M , Häggblom Max M , Smidt Hauke , Atashgahi Siavash 
Published: January 2020

Abstract
The genus Desulfoluna comprises two anaerobic sulfate-reducing strains, D. spongiiphila AA1T and D. butyratoxydans MSL71T, of which only the former was shown to perform organohalide respiration (OHR). Here we isolated a third strain, designated D. spongiiphila strain DBB, from marine intertidal sediment using 1,4-dibromobenzene and sulfate as the electron acceptors and lactate as the electron donor. Each strain harbors three reductive dehalogenase gene clusters (rdhABC) and corrinoid biosynthesis genes in their genomes, and dehalogenated brominated but not chlorinated organohalogens. The Desulfoluna strains maintained OHR in the presence of 20 mM sulfate or 20 mM sulfide, which often negatively affect other organohalide-respiring bacteria. Strain DBB sustained OHR with 2% oxygen in the gas phase, in line with its genetic potential for reactive oxygen species detoxification. Reverse transcription-quantitative PCR revealed differential induction of rdhA genes in strain DBB in response to 1,4-dibromobenzene or 2,6-dibromophenol. Proteomic analysis confirmed expression of rdhA1 with 1,4-dibromobenzene, and revealed a partially shared electron transport chain from lactate to 1,4-dibromobenzene and sulfate, which may explain accelerated OHR during concurrent sulfate reduction. Versatility in using electron donors, de novo corrinoid biosynthesis, resistance to sulfate, sulfide and oxygen, and concurrent sulfate reduction and OHR may confer an advantage to marine Desulfoluna strains.
Mountain biodiversity and ecosystem functions: interplay between geology and contemporary environments
Authors: Hu Ang , Wang Jianjun , Sun Hang , Niu Bin , Si Guicai , Wang Jian , Yeh Chih-Fu , Zhu Xinxin , Lu Xiancai , Zhou Jizhong , Yang Yongping , Ren Minglei , Hu Yilun , Dong Hailiang , Zhang Gengxin 
Published: January 2020

Abstract
Although biodiversity and ecosystem functions are strongly shaped by contemporary environments, such as climate and local biotic and abiotic attributes, relatively little is known about how they depend on long-term geological processes. Here, along a 3000-m elevational gradient with tectonic faults on the Tibetan Plateau (that is, Galongla Mountain in Medog County, China), we study the joint effects of geological and contemporary environments on biological communities, such as the diversity and community composition of plants and soil bacteria, and ecosystem functions. We find that these biological communities and ecosystem functions generally show consistent elevational breakpoints at 2000–2800 m, which coincide with Indus-Yalu suture zone fault and are similar to the elevational breakpoints of soil bacteria on another mountain range 1000 km away. Mean annual temperature, soil pH and moisture are the primary contemporary determinants of biodiversity and ecosystem functions, which support previous findings. However, compared with the models excluding geological processes, inclusion of geological effects, such as parent rock and weathering, increases 67.9 and 35.9% of the explained variations in plant and bacterial communities, respectively. Such inclusion increases 27.6% of the explained variations in ecosystem functions. The geological processes thus provide additional links to ecosystem properties, which are prominent but show divergent effects on biodiversity and ecosystem functions: parent rock and weathering exert considerable direct effects on biodiversity, whereas indirectly influence ecosystem functions via interactions with biodiversity and contemporary environments. Thus, the integration of geological processes with environmental gradients could enhance our understanding of biodiversity and, ultimately, ecosystem functioning across different climatic zones.
Compensatory mutations modulate the competitiveness and dynamics of plasmid-mediated colistin resistance in Escherichia coli clones
Authors: Yang Qiu E , MacLean Craig , Papkou Andrei , Pritchard Manon , Powell Lydia , Thomas David , Andrey Diego O , Li Mei , Spiller Brad , Yang Wang , Walsh Timothy R 
Published: January 2020

Abstract
The emergence of mobile colistin resistance (mcr) threatens to undermine the clinical efficacy of the last antibiotic that can be used to treat serious infections caused by Gram-negative pathogens. Here we measure the fitness cost of a newly discovered MCR-3 using in vitro growth and competition assays. mcr-3 expression confers a lower fitness cost than mcr-1, as determined by competitive ability and cell viability. Consistent with these findings, plasmids carrying mcr-3 have higher stability than mcr-1 plasmids across a range of Escherichia coli strains. Crucially, mcr-3 plasmids can stably persist, even in the absence of colistin. Recent compensatory evolution has helped to offset the cost of mcr-3 expression, as demonstrated by the high fitness of mcr-3.5 as opposed to mcr-3.1. Reconstructing all of the possible evolutionary trajectories from mcr-3.1 to mcr-3.5 reveals a complex fitness landscape shaped by negative epistasis between compensatory and neutral mutations. Our findings highlight the importance of fitness costs and compensatory evolution in driving the dynamics and stability of mobile colistin resistance in bacterial populations, and they highlight the need to understand how processes (other than colistin use) impact mcr dynamics.
The roles of RNA in DNA double-strand break repair
Authors: Bader Aldo S. , Hawley Ben R. , Wilczynska Ania , Bushell Martin 
Published: January 2020

AbstractEffective DNA repair is essential for cell survival: a failure to correctly repair damage leads to the accumulation of mutations and is the driving force for carcinogenesis. Multiple pathways have evolved to protect against both intrinsic and extrinsic genotoxic events, and recent developments have highlighted an unforeseen critical role for RNA in ensuring genome stability. It is currently unclear exactly how RNA molecules participate in the repair pathways, although many models have been proposed and it is possible that RNA acts in diverse ways to facilitate DNA repair. A number of well-documented DNA repair factors have been described to have RNA-binding capacities and, moreover, screens investigating DNA-damage repair mechanisms have identified RNA-binding proteins as a major group of novel factors involved in DNA repair. In this review, we integrate some of these datasets to identify commonalities that might highlight novel and interesting factors for future investigations. This emerging role for RNA opens up a new dimension in the field of DNA repair; we discuss its impact on our current understanding of DNA repair processes and consider how it might influence cancer progression.
B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids
Authors: Sanchez Helia N. , Moroney Justin B. , Gan Huoqun , Shen Tian , Im John L. , Li Tianbao , Taylor Julia R. , Zan Hong , Casali Paolo 
Published: January 2020

AbstractShort-chain fatty acids (SCFAs) butyrate and propionate are metabolites from dietary fiber's fermentation by gut microbiota that can affect differentiation or functions of T cells, macrophages and dendritic cells. We show here that at low doses these SCFAs directly impact B cell intrinsic functions to moderately enhance class-switch DNA recombination (CSR), while decreasing at higher doses over a broad physiological range, AID and Blimp1 expression, CSR, somatic hypermutation and plasma cell differentiation. In human and mouse B cells, butyrate and propionate decrease B cell Aicda and Prdm1 by upregulating select miRNAs that target Aicda and Prdm1 mRNA-3′UTRs through inhibition of histone deacetylation (HDAC) of those miRNA host genes. By acting as HDAC inhibitors, not as energy substrates or through GPR-engagement signaling in these B cell-intrinsic processes, these SCFAs impair intestinal and systemic T-dependent and T-independent antibody responses. Their epigenetic impact on B cells extends to inhibition of autoantibody production and autoimmunity in mouse lupus models.
Conjunction of triboelectric nanogenerator with induction coils as wireless power sources and self-powered wireless sensors
Authors: Zhang Chi , Chen Jinkai , Xuan Weipeng , Huang Shuyi , You Bin , Li Wenjun , Sun Lingling , Jin Hao , Wang Xiaozhi , Dong Shurong , Luo Jikui , Flewitt A. J. , Wang Zhong Lin 
Published: January 2020

AbstractHere we demonstrate a magnetic resonance coupling based wireless triboelectric nanogenerator (TENG) and fully self-powered wireless sensors. By integrating a microswitch and an inductor with the TENG, the pulsed voltage output is converted into a sinusoidal voltage signal with a fixed frequency. This can be transmitted wirelessly from the transmit coil to the resonant-coupled receiver coil with an efficiency of 73% for a 5 cm distance between the two coils (10 cm diameter). Analytic models of the oscillating and coupled voltage signals for the wireless energy transfer are developed, showing excellent agreement with the experimental results. A TENG of 40 × 50 mm2 can wirelessly light up 70 LEDs or charge up a 15 μF capacitor to 12.5 V in ~90 s. The system is further utilized for two types of fully self-powered wireless chipless sensors with no microelectronic components. The technologies demonstrate an innovative strategy for a wireless ‘green’ power source and sensing.
In vivo functional analysis of non-conserved human lncRNAs associated with cardiometabolic traits
Authors: Ruan Xiangbo , Li Ping , Chen Yi , Shi Yu , Pirooznia Mehdi , Seifuddin Fayaz , Suemizu Hiroshi , Ohnishi Yasuyuki , Yoneda Nao , Nishiwaki Megumi , Shepherdson James , Suresh Abhilash , Singh Komudi , Ma Yonghe , Jiang Cheng-fei , Cao Haiming 
Published: January 2020

AbstractUnlike protein-coding genes, the majority of human long non-coding RNAs (lncRNAs) are considered non-conserved. Although lncRNAs have been shown to function in diverse pathophysiological processes in mice, it remains largely unknown whether human lncRNAs have such in vivo functions. Here, we describe an integrated pipeline to define the in vivo function of non-conserved human lncRNAs. We first identify lncRNAs with high function potential using multiple indicators derived from human genetic data related to cardiometabolic traits, then define lncRNA’s function and specific target genes by integrating its correlated biological pathways in humans and co-regulated genes in a humanized mouse model. Finally, we demonstrate that the in vivo function of human-specific lncRNAs can be successfully examined in the humanized mouse model, and experimentally validate the predicted function of an obesity-associated lncRNA, LINC01018, in regulating the expression of genes in fatty acid oxidation in humanized livers through its interaction with RNA-binding protein HuR.
Retinoic acid degradation shapes zonal development of vestibular organs and sensitivity to transient linear accelerations
Authors: Ono Kazuya , Keller James , López Ramírez Omar , González Garrido Antonia , Zobeiri Omid A. , Chang Hui Ho Vanessa , Vijayakumar Sarath , Ayiotis Andrianna , Duester Gregg , Della Santina Charles C. , Jones Sherri M. , Cullen Kathleen E. , Eatock Ruth Anne , Wu Doris K. 
Published: January 2020

AbstractEach vestibular sensory epithelium in the inner ear is divided morphologically and physiologically into two zones, called the striola and extrastriola in otolith organ maculae, and the central and peripheral zones in semicircular canal cristae. We found that formation of striolar/central zones during embryogenesis requires Cytochrome P450 26b1 (Cyp26b1)-mediated degradation of retinoic acid (RA). In Cyp26b1 conditional knockout mice, formation of striolar/central zones is compromised, such that they resemble extrastriolar/peripheral zones in multiple features. Mutants have deficient vestibular evoked potential (VsEP) responses to jerk stimuli, head tremor and deficits in balance beam tests that are consistent with abnormal vestibular input, but normal vestibulo-ocular reflexes and apparently normal motor performance during swimming. Thus, degradation of RA during embryogenesis is required for formation of highly specialized regions of the vestibular sensory epithelia with specific functions in detecting head motions.
Measuring local-directional resolution and local anisotropy in cryo-EM maps
Authors: Vilas Jose Luis , Tagare Hemant D. , Vargas Javier , Carazo Jose Maria , Sorzano Carlos Oscar S. 
Published: January 2020

AbstractThe introduction of local resolution has enormously helped the understanding of cryo-EM maps. Still, for any given pixel it is a global, aggregated value, that makes impossible the individual analysis of the contribution of the different projection directions. We introduce MonoDir, a fully automatic, parameter-free method that, starting only from the final cryo-EM map, decomposes local resolution into the different projection directions, providing a detailed level of analysis of the final map. Many applications of directional local resolution are possible, and we concentrate here on map quality and validation.
Identification of recurrent FHL2-GLI2 oncogenic fusion in sclerosing stromal tumors of the ovary
Authors: Kim Sarah H. , Da Cruz Paula Arnaud , Basili Thais , Dopeso Higinio , Bi Rui , Pareja Fresia , da Silva Edaise M. , Gularte-Mérida Rodrigo , Sun Zhen , Fujisawa Sho , Smith Caitlin G. , Ferrando Lorenzo , Martins Sebastião Ana Paula , Bykov Yonina , Li Anqi , Silveira Catarina , Ashley Charles W. , Stylianou Anthe , Selenica Pier , Samore Wesley R. , Jungbluth Achim A. , Zamarin Dmitriy , Abu-Rustum Nadeem R. , Helin Kristian , Soslow Robert A. , Reis-Filho Jorge S. , Oliva Esther , Weigelt Britta 
Published: January 2020

AbstractSclerosing stromal tumor (SST) of the ovary is a rare type of sex cord-stromal tumor (SCST), whose genetic underpinning is currently unknown. Here, using whole-exome, targeted capture and RNA-sequencing, we report recurrent FHL2-GLI2 fusion genes in 65% (17/26) of SSTs and other GLI2 rearrangements in additional 15% (4/26) SSTs, none of which are detected in other types of SCSTs (n = 48) or common cancer types (n = 9,950). The FHL2-GLI2 fusions result in transcriptomic activation of the Sonic Hedgehog (SHH) pathway in SSTs. Expression of the FHL2-GLI2 fusion in vitro leads to the acquisition of phenotypic characteristics of SSTs, increased proliferation, migration and colony formation, and SHH pathway activation. Targeted inhibition of the SHH pathway results in reversal of these oncogenic properties, indicating its role in the pathogenesis of SSTs. Our results demonstrate that the FHL2-GLI2 fusion is likely the oncogenic driver of SSTs, defining a genotypic–phenotypic correlation in ovarian neoplasms.
An artificial spiking afferent nerve based on Mott memristors for neurorobotics
Authors: Zhang Xumeng , Zhuo Ye , Luo Qing , Wu Zuheng , Midya Rivu , Wang Zhongrui , Song Wenhao , Wang Rui , Upadhyay Navnidhi K. , Fang Yilin , Kiani Fatemeh , Rao Mingyi , Yang Yang , Xia Qiangfei , Liu Qi , Liu Ming , Yang J. Joshua 
Published: January 2020

AbstractNeuromorphic computing based on spikes offers great potential in highly efficient computing paradigms. Recently, several hardware implementations of spiking neural networks based on traditional complementary metal-oxide semiconductor technology or memristors have been developed. However, an interface (called an afferent nerve in biology) with the environment, which converts the analog signal from sensors into spikes in spiking neural networks, is yet to be demonstrated. Here we propose and experimentally demonstrate an artificial spiking afferent nerve based on highly reliable NbOx Mott memristors for the first time. The spiking frequency of the afferent nerve is proportional to the stimuli intensity before encountering noxiously high stimuli, and then starts to reduce the spiking frequency at an inflection point. Using this afferent nerve, we further build a power-free spiking mechanoreceptor system with a passive piezoelectric device as the tactile sensor. The experimental results indicate that our afferent nerve is promising for constructing self-aware neurorobotics in the future.
Genome-scale reconstructions of the mammalian secretory pathway predict metabolic costs and limitations of protein secretion
Authors: Gutierrez Jahir M. , Feizi Amir , Li Shangzhong , Kallehauge Thomas B. , Hefzi Hooman , Grav Lise M. , Ley Daniel , Baycin Hizal Deniz , Betenbaugh Michael J. , Voldborg Bjorn , Faustrup Kildegaard Helene , Min Lee Gyun , Palsson Bernhard O. , Nielsen Jens , Lewis Nathan E. 
Published: January 2020

AbstractIn mammalian cells, >25% of synthesized proteins are exported through the secretory pathway. The pathway complexity, however, obfuscates its impact on the secretion of different proteins. Unraveling its impact on diverse proteins is particularly important for biopharmaceutical production. Here we delineate the core secretory pathway functions and integrate them with genome-scale metabolic reconstructions of human, mouse, and Chinese hamster ovary cells. The resulting reconstructions enable the computation of energetic costs and machinery demands of each secreted protein. By integrating additional omics data, we find that highly secretory cells have adapted to reduce expression and secretion of other expensive host cell proteins. Furthermore, we predict metabolic costs and maximum productivities of biotherapeutic proteins and identify protein features that most significantly impact protein secretion. Finally, the model successfully predicts the increase in secretion of a monoclonal antibody after silencing a highly expressed selection marker. This work represents a knowledgebase of the mammalian secretory pathway that serves as a novel tool for systems biotechnology.