bluuebunny/crossref_metadata_2025_split huggingface dataset:
A precisely adjustable, variation-suppressed eukaryotic transcriptional controller to enable genetic discovery
Authors: Azizoğlu Asli , Brent Roger , Rudolf Fabian 
Published: December 2019

AbstractMethods to express genes conditionally into phenotype remain central to biological experimentation and biotechnology. Current methods enable either on/off or imprecisely controlled graded gene expression. We developed a “well-tempered” controller, WTC846, for precisely adjustable, graded and growth condition independent conditional expression of genes inSaccharomyces cerevisiae. In WTC846strains, the controlled genes are expressed from a strong, native promoter engineered to be repressed by the prokaryotic TetR protein and induced by tetracycline and analogues. A second instance of this promoter drives TetR itself. This autorepression loop exhibits low cell-to-cell variation in gene expression and allows precise adjustment of the steady state abundance of any protein with inducer. A second, constitutively expressed zeroing repressor abolishes basal expression in the absence of inducer. WTC846-controlled, stable (Cdc42, Tpi1) and unstable (Ipl1) proteins recapitulated known knockout and overexpression phenotypes.WTC846::CDC20strains enabled inducer regulated cell cycle synchronization. WTC846alleles ofCDC28,TOR1,PBR1andPMA1exhibited expected gene dosage-dependent growth rates and morphological phenotypes, andWTC846::WHI5strains exhibited inducer controlled differences in cell volume. WTC846controlled genes comprise a new kind of “expression clamped” allele, for which variation in expression is minimized and gene dosage can be set by the experimenter across the range of cellular protein abundances. In yeast, we expect WTC846alleles to find use in assessment of phenotypes now incompletely penetrant due to variable dosage of the causative protein, and in genome-wide epistasis screens. Implementation in higher cells should enable experiments now impossible due to cell-to-cell variation and imprecise control.
A fast and simple method for detecting identity by descent segments in large-scale data
Authors: Zhou Ying , Browning Sharon R. , Browning Brian L. 
Published: December 2019

AbstractSegments of identity by descent (IBD) are used in many genetic analyses. We present a method for detecting identical-by-descent haplotype segments that is optimized for large-scale genotype data. Our method, called hap-IBD, combines a compressed representation of genotype data, the positional Burrows-Wheeler transform, and multi-threaded execution to produce very fast analysis times. An attractive feature of hap-IBD is its simplicity: the input parameters clearly and precisely define the IBD segments that are reported, so that program correctness can be confirmed by users.We evaluate hap-IBD and four state-of-the-art IBD segment detection methods (GERMLINE, iLASH, RaPID, and TRUFFLE) using UK Biobank chromosome 20 data and simulated sequence data. We show that hap-IBD detects IBD segments faster and more accurately than competing methods, and that hap-IBD is the only method that can rapidly and accurately detect short 2-4 cM IBD segments in the full UK Biobank data. Analysis of 485,346 UK Biobank samples using hap-IBD with 12 computational threads detects 231.5 billion autosomal IBD segments with length ≥2 cM in 24.4 hours.
ASTRAL-Pro: quartet-based species tree inference despite paralogy
Authors: Zhang Chao , Scornavacca Celine , Molloy Erin K. , Mirarab Siavash 
Published: December 2019

AbstractSpecies tree inference via summary methods that combine gene trees has become an increasingly common analysis in recent phylogenomic studies. This broad adoption has been partly due to the greater availability of genome-wide data and ample recognition that gene trees and species trees can differ due to biological processes such as gene duplication and gene loss. This increase has also been encouraged by the recent development of accurate and scalable summary methods, such as ASTRAL. However, most of these methods, including ASTRAL, can only handle single-copy gene trees and do not attempt to model gene duplication and gene loss. In this paper, we introduce a measure of quartet similarity between single-copy and multi-copy trees (accounting for orthology and paralogy relationships) that can be optimized via a scalable dynamic programming similar to the one used by ASTRAL. We then present a new quartet-based species tree inference method: ASTRAL-Pro (ASTRAL for PaRalogs and Orthologs). By studying its performance on an extensive collection of simulated datasets and on a real plant dataset, we show that ASTRAL-Pro is more accurate than alternative methods when gene trees differ from the species tree due to the simultaneous presence of gene duplication, gene loss, incomplete lineage sorting, and estimation errors.
Phase of Firing Coding of Learning Variables across Prefrontal Cortex, Anterior Cingulate Cortex and Striatum during Feature Learning
Authors: Voloh Benjamin , Oemisch Mariann , Womelsdorf Thilo 
Published: December 2019

AbstractThe prefrontal cortex and striatum form a recurrent network whose spiking activity encodes multiple types of learning-relevant information. This spike-encoded information is evident in average firing rates, but finer temporal coding might allow multiplexing and enhanced readout across the connected the network. We tested this hypothesis in the fronto-striatal network of nonhuman primates during reversal learning of feature values. We found that neurons encoding current choice outcomes, outcome prediction errors, and outcome history in their firing rates also carried significant information in their phase-of-firing at a 10-25 Hz beta frequency at which they synchronized across lateral prefrontal cortex, anterior cingulate cortex and striatum. The phase-of-firing code exceeded information that could be obtained from firing rates alone, was strong for inter-areal connections, and multiplexed information at three different phases of the beta cycle that were offset from the preferred spiking phase of neurons. Taken together, these findings document the multiplexing of three different types of information in the phase-of-firing at an interareally shared beta oscillation frequency during goal-directed behavior.HighlightsLateral prefrontal cortex, anterior cingulate cortex and striatum show phase-of-firing encoding for outcome, outcome history and reward prediction errors.Neurons with phase-of-firing code synchronize long-range at 10-25 Hz.Spike phases encoding reward prediction errors deviate from preferred synchronization phases.Anterior cingulate cortex neurons show strongest long-range effects.
PREDATION CAPACITY OF SOIL-DWELLING PREDATORY MITES ON TWO GROUND BEETLE IMMATURE STAGES: A BIOLOGICAL CONTROL PERSPECTIVE FOR TWO MAJOR MAIZE PESTS
Authors: Pasquier Antoine , Andrieux Thibault , Martinez-Rodriguez Paloma , Vercken Elodie , Ferrero Maxime 
Published: December 2019

ABSTRACTSoil-dwelling predatory mites already proved their efficiency as biocontrol agents against many pests (Carrillo et al. 2015). Western Corn Rootworm (WCR), (Diabrotica virgifera virgifera)and Wireworm (WW) (Agriotes sordidus) are important pests of various crops (Furlan et al. 2002; Krysan et al., 1986; Ritter and Richter 2013; Wesseler and Fall 2010) whose eggs and first instar larvae also inhabit the first centimeters of soil (Furlan 2004; Vidal et al., 2005). In order to evaluate the potential of predatory mites as biological control agents against WCR and WW, we investigated the predation capacity ofStratiolaelaps scimitus,Gaeolaelaps aculeiferandMacrocheles robustuluson immature stages of these two prey species. First, we observed if one or more species could feed upon eggs and first instar larvae as Prischmann et al. (2011) suggested for WCR. We then explored their predation abilities through time using a survival analysis to identify the best biocontrol agent among the species tested.Surprisingly, none of the predator species tested identified WCR or WW eggs as preys. However, at least 50% of WCR and WW first instar larvae have been attacked byG. aculeiferandM. robustulus.Stratiolaelaps scimitusshowing a slightly lower efficiency (30% of preys attacked). The survival analysis confirmed this trend with slower predation dynamics forS. scimitus.These results show a potential of soil-dwelling predatory mites as biocontrol agents against WCR and WW. Furthermore, targeting the neonate stage instead of the egg stage in pest management strategies seems necessary for maximizing efficiency.
AFM images of open and collapsed states of yeast condensin suggest a scrunching model for DNA loop extrusion
Authors: Ryu Je-Kyung , Katan Allard J. , van der Sluis Eli O. , Wisse Thomas , de Groot Ralph , Haering Christian , Dekker Cees 
Published: December 2019

SUMMARYStructural Maintenance of Chromosome (SMC) protein complexes are the key organizers of the spatiotemporal structure of chromosomes. The condensin SMC complex, which compacts DNA during mitosis, was recently shown to be a molecular motor that extrudes large loops of DNA. The mechanism of this unique motor, which takes large steps along DNA at low ATP consumption, remains elusive however. Here, we use Atomic Force Microscopy (AFM) to visualize the structure of yeast condensin and condensin-DNA complexes. Condensin is found to exhibit mainly open ‘O’ shapes and collapsed ‘B’ shapes, and it cycles dynamically between these two states over time. Condensin binds double-stranded DNA via a HEAT subunit and, surprisingly, also via the hinge domain. On extruded DNA loops, we observe a single condensin complex at the loop stem, where the neck size of the DNA loop correlates with the width of the condensin complex. Our results suggest that condensin extrudes DNA by a fast cyclic switching of its conformation between O and B shapes, consistent with a scrunching model.
Millet-based supplement restored microbiota diversity of acute undernourished pigs
Authors: Li Xuejing , Hui Yan , Ren JunLi , Song Yanni , Liu Songling , Che Lianqiang , Peng Xi , Dai Xiaoshuang 
Published: December 2019

AbstractThe strong connection between undernutrition and gut microbiota (GM) has enabled microbiota-targeting to become an evolving strategy, which witnessed urgent need for fortified formula of supplementary food in undernutrition therapy. Using undernourished pigs as models, we investigated how corn- and millet-based nutritional supplement acted differently in modulating microbiota. Undernourished pigs at age of 9 weeks were fed with pure maize diet (Maize), corn-based (CSB+) and millet-based (MSB+) supplementary food for 3 weeks. Compared with Maize group, both CSB+ and MSB+ improved serum total protein and globulin level, but no physiological improvement was observed by short-term food intervention. MSB+ shown superior influence on GM immaturity which were more normally-grown like at both structural and functional level. Higher level of Bacteriodetes, Firmicutes and lower level of Preteobacteria were detected in MSB+ fed piglets in contrast with CSB+.Lachnospira.sppwas significantly raised after nutritional intervention, indicating high correlation with the undernutrition-associated phenotype. Thus, especially from the GM aspect, millet could be one promising source to help undernourished children reconstruct balanced microbiota in short therapeutic term.
Systems-level analysis of peripheral blood gene expression in dementia patients reveals an innate immune response shared across multiple disorders
Authors: Nachun D , Ramos EM , Karydas A , Dokuru D , Gao F , Yang Z , Van Berlo V , Sears R , Kramer J , Boxer AL , Rosen H , Miller BL , Coppola G. 
Published: December 2019

AbstractThe role of peripheral inflammation in dementia is an important but complex topic. We present here the largest cohort of peripheral blood gene expression data ever assembled from patients with dementia and matching controls. Importantly, this cohort includes individuals from a diverse set of dementia disorders, including Alzheimer’s Disease (AD), mild cognitive impairment (MCI), and multiple disorders within the frontotemporal dementia (FTD) spectrum. We found strong transcriptional evidence of an innate immune inflammatory response, mediated by monocytes and neutrophils, in AD, MCI, and two FTD subtypes, PSP and nfvPPA. This transcriptional inflammatory response is enriched for genetic risk for AD, in part because it is also enriched for microglial genes, which have previously been implicated in AD risk. Finally, we show that this transcriptional response is strongly enriched for binding of the transcription factors PU.1 and RELA, which have previously been linked to AD risk and progression.
Early life adversity and borderline intellectual functioning negatively impact limbic system connectivity in childhood: a connectomics-based study
Authors: Blasi Valeria , Pirastru Alice , Cabinio Monia , Di Tella Sonia , Laganà Maria Marcella , Giangiacomo Alice , Baglio Gisella , Zanette Michela , Canevini Maria Paola , Walder Mauro , Clerici Mario , Baglio Francesca 
Published: December 2019

AbstractEpigenetic factors related to early life adversity (ELA) in childhood are major risk factors for borderline intellectual functioning (BIF). BIF affects both adaptive and intellectual abilities, commonly leading to school failure and to an increased risk to develop mental and social problems in the adulthood. This study aimed to investigate the neurobiological underpinnings of ELA associated with BIF in terms of global topological organization and structural connectivity and their relation with intellectual functioning.BIF (N=32) and age-matched typical development (TD, N=14) children were evaluated for intelligence quotient (IQ), behavioral competencies, and ELA. Children underwent an anatomical and diffusion-weighted MR imaging (DWI) protocol. Global brain topological organization was assessed measuring segregation and integration indexes. Moreover, structural matrices, measuring normalized number of fibers (NFn), were compared between the 2 groups using network-based statistics. Finally, a linear regression model was used to explore the relationship between network parameters and clinical measures.Results showed increased behavioral difficulties and ELA, together with decreased network integration in BIF children. Moreover, significantly lower NFn was observed in the BIF group (p=.039) in a sub-network comprising anterior and posterior cingulate, the pericallosal sulcus, the orbital frontal areas, amygdala, basal ganglia, the accumbens nucleus, and the hippocampus. Linear regression showed that NFn significantly predicted IQ (p<.0001).This study demonstrated that ELA in children with BIF is associated with a decreased information integration at the global level, and with an altered structural connectivity within the limbic system strictly related to the intellectual functioning.
Impaired cholesterol metabolism in the mice model of cystic fibrosis. A vicious circle?
Authors: Amato Felice , Castaldo Alice , Castaldo Giuseppe , Cernera Gustavo , Corso Gaetano , Ferrari Eleonora , Gelzo Monica , Monzani Romina , Villella Valeria Rachela , Raia Valeria 
Published: December 2019

AbstractPatients with cystic fibrosis (CF) have low cholesterol absorption and, despite enhanced endogenous biosynthesis, low serum cholesterol. Herein, we investigated cholesterol metabolism in a murine CF model in comparison towild type(WT) testing serum and liver surrogate biomarkers together with the hepatic expression of genes involved in cholesterol metabolism. CF mice display lower sterols absorption and increased endogenous biosynthesis. Subsequently, we evaluated the effects of a cholesterol-supplemented diet on cholesterol metabolism in CF and WT mice. The supplementation in WT mice determines biochemical changes similar to humans. Instead, CF mice with supplementation did not show significant changes, except for serum phytosterols (−50%), liver cholesterol (+35%) and TNFα mRNA expression, that resulted 5-fold higher than in CF without supplementation. However, liver cholesterol in CF mice with supplementation resulted significantly lower compared to WT supplemented mice. This study shows that in CF mice there is a vicious circle in which the altered bile salts synthesis/secretion contribute to reduce cholesterol digestion/absorption. The consequence is the enhanced liver cholesterol biosynthesis that accumulates in the cell triggering inflammation.
Glucose starvation to rapid death of Nrf1, but not Nrf2, deficient hepatoma cells from its fatal defects in the redox metabolism reprogramming
Authors: Zhu Yu-ping , Zheng Ze , Xiang Yuancai , Zhang Yiguo 
Published: December 2019

AbstractMetabolic reprogramming exists in a variety of cancer cells, with the most relevance to glucose as a source of energy and carbon for survival and proliferation. Of note, Nrf1 was shown to be essential for regulating glycolysis pathway, but it is unknown whether it plays a role in cancer metabolic reprogramming, particularly in response to glucose starvation. Herein, we discover thatNrf1α−/−-derived hepatoma cells are sensitive to rapid death induced by glucose deprivation, such cell death appears to be rescued byNrf2interference, butNrf1/2+/+orNrf2−/−-derived cells are roughly unaffected by glucose starvation. Further evidence revealed thatNrf1α−/−cell death is resulted from severe oxidative stress arising from abberrant redox metabolism. Strikingly, altered gluconeogenesis pathway was aggravated by glucose starvation ofNrf1α−/−cells, as also accompanied by weakened pentose phosphate pathway, dysfunction of serine-to-glutathione synthesis, and accumulation of reactive oxygen species (ROS) and damages, such that the intracellular GSH and NADPH were exhausted. These demonstrate that glucose starvation leads to acute death ofNrf1α−/−, rather thanNrf2−/−, cells resulting from its fatal defects in the redox metabolism reprogramming. This is owing to distinct requirements of Nrf1 and Nrf2 for regulating key genes involved in the redox metabolic reprogramming. Altogether, this work substantiates the preventive and therapeutic strategies againstNrf1α-deficient cancer by limiting its glucose and energy demands.
Inositol pyrophosphates promote the interaction of SPX domains with the coiled-coil motif of PHR transcription factors to regulate plant phosphate homeostasis
Authors: Ried Martina K. , Wild Rebekka , Zhu Jinsheng , Broger Larissa , Harmel Robert K. , Hothorn Ludwig A. , Fiedler Dorothea , Hothorn Michael 
Published: December 2019

AbstractPhosphorus is an essential nutrient taken up by organisms in the form of inorganic phosphate (Pi). Eukaryotes have evolved sophisticated Pi sensing and signalling cascades, enabling them to maintain cellular Pi concentrations. Pi homeostasis is regulated by inositol pyrophosphate signalling molecules (PP-InsPs), which are sensed by SPX-domain containing proteins. In plants, PP-InsP bound SPX receptors inactivate Myb coiled-coil (MYB-CC) Pi starvation response transcription factors (PHRs) by an unknown mechanism. Here we report that a InsP8– SPX complex targets the plant-unique CC domain of PHRs. Crystal structures of the CC domain reveal an unusual four-stranded anti-parallel arrangement. Interface mutations in the CC domain yield monomeric PHR1, which is no longer able to bind DNA with high affinity. Mutation of conserved basic residues located at the surface of the CC domain disrupt interaction with the SPX receptorin vitroandin planta, resulting in constitutive Pi starvation responses. Together, our findings suggest that InsP8regulates plant Pi homeostasis by controlling the oligomeric state and hence the promoter binding capability of PHRs via their SPX receptors. (173 words)
The compact genome ofGiardia murisreveals important steps in the evolution of intestinal protozoan parasites
Authors: Xu Feifei , Jiménez-González Alejandro , Einarsson Elin , Ástvaldsson Ásgeir , Peirasmaki Dimitra , Eckmann Lars , Andersson Jan O. , Svärd Staffan G. , Jerlström-Hultqvist Jon 
Published: December 2019

AbstractDiplomonad parasites of the genusGiardiahave adapted to colonizing different hosts, most notably the intestinal tract of mammals. The human-pathogenicGiardiaspecies,Giardia intestinalis, has been extensively studied at the genome and gene expression level, but no such information is available for otherGiardiaspecies. Comparative data would be particularly valuable forGiardia muris, which colonizes mice and is commonly used as a prototypicin vivomodel for investigating host responses to intestinal parasitic infection. Here we report the draft-genome ofG. muris. We discovered a highly streamlined genome, amongst the most densely encoded ever described for a nuclear eukaryotic genome.G. murisandG. intestinalisshare many known or predicted virulence factors, including cysteine proteases and a large repertoire of cysteine-rich surface proteins involved in antigenic variation. Different toG. intestinalis, G. murismaintains tandem arrays of pseudogenized surface antigens at the telomeres, whereas intact surface antigens are present centrally in the chromosomes. The two classes of surface antigens engage in genetic exchange. Reconstruction of metabolic pathways from theG. murisgenome suggest significant metabolic differences toG. intestinalis. Additionally,G. murisencodes proteins that might be used to modulate the prokaryotic microbiota. The responsible genes have been introduced in theGiardiagenus via lateral gene transfer from prokaryotic sources. Our findings point to important evolutionary steps in theGiardiagenus as it adapted to different hosts and it provides a powerful foundation for mechanistic exploration of host-pathogen interaction in theG. muris– mouse pathosystem.Author summaryTheGiardiagenus comprises eukaryotic single-celled parasites that infect many animals. TheGiardia intestinalisspecies complex, which can colonize and cause diarrheal disease in humans and different animal hosts has been extensively explored at the genomic and cell biologic levels. OtherGiardiaspecies, such as the mouse parasiteGiardia muris, have remained uncharacterized at the genomic level, hampering our understanding ofin vivohost-pathogen interactions and the impact of host dependence on the evolution of theGiardiagenus. We discovered that theG. murisgenome encodes many of the same virulence factors asG. intestinalis. TheG. murisgenome has undergone genome contraction, potentially in response to a more defined infective niche in the murine host. We describe differences in metabolic and microbiome modulatory gene repertoire, mediated mainly by lateral gene transfer, that could be important for understanding infective success across theGiardiagenus. Our findings provide new insights for the use ofG. murisas a powerful model for exploring host-pathogen interactions in giardiasis.