bluuebunny/crossref_metadata_2025_split huggingface dataset:
Higher-order effects, continuous species interactions, and trait evolution shape microbial spatial dynamics
Authors: Swain Anshuman , Fussell Levi , Fagan William F 
Published: February 2021

AbstractThe assembly and maintenance of microbial diversity in natural communities, despite the abundance of toxin-based antagonistic interactions, presents major challenges for biological understanding. A common framework for investigating such antagonistic interactions involve cyclic dominance games with pairwise interactions. The incorporation of higher-order interactions in such models permits increased levels of microbial diversity, especially in communities where antibiotic producing, sensitive, and resistant strains co-exist. However, most such models involve a small number of discrete species, assume a notion of pure cyclic dominance, and focus on low mutation rate regimes, none of which well represents the highly interlinked, quickly evolving, and continuous nature of microbial phenotypic space. Here, we present an alternative vision of spatial dynamics for microbial communities based on antagonistic interactions—one in which a large number of species interact in continuous phenotypic space, are capable of rapid mutation, and engage in both direct and higher-order interactions mediated by production of and resistance to antibiotics. Focusing on toxin production, vulnerability, and inhibition among species, we observe highly divergent patterns of diversity and spatial community dynamics. We find that species interaction constraints (rather than mobility) best predict spatiotemporal disturbance regimes, whereas community formation time, mobility, and mutation size best explain patterns of diversity. We also report an intriguing relationship among community formation time, spatial disturbance regimes, and diversity dynamics. This relationship, which suggests that both higher-order interactions and rapid evolution are critical for the origin and maintenance of microbial diversity, has broad-ranging links to the maintenance of diversity in other systems.Significance StatementPersistently diverse microbial communities are one of biology’s great puzzles. Using a novel continuous trait space modeling framework that accommodates high mutation rates, elevated species richness, and direct and higher-order antagonistic species interactions, we find that two parameters characterizing mutation size and mobility best explain patterns of microbial diversity. Moreover, community formation time (the duration of the transient phase in community assembly) provides an unexpectedly clear guide to the diversity profiles of the resulting communities. These discoveries showcase how complex, antagonistic interactions mediated by the production of, inhibition of, and vulnerability to toxins (antibiotics) can shape microbial communities, allowing for extraordinarily high levels of diversity and temporal persistence.
A development guide for evaluating the maximum yield potential stage in barley
Authors: Thirulogachandar Venkatasubbu , Schnurbusch Thorsten 
Published: February 2021

AbstractDetermining the grain yield potential contributed by grain number is a step towards advancing cereal crops’ yield. To achieve this aim, it is pivotal to recognize the maximum yield potential (MYP) of the crop. In barley (Hordeum vulgareL.), the MYP is defined as the maximum spikelet primordia number of a spike. Previous barley studies often assumed the awn primordium (AP) stage as the MYP stage regardless of genotypes and growth conditions. From our spikelet-tracking experiments using the two-rowed cultivar Bowman, we found that the MYP stage can be different from the AP stage. Importantly, we find that the occurrence of inflorescence meristem (IM) deformation and its loss of activity coincided with the MYP stage, indicating the end of further spikelet initiation. Thus, we recommend validating the barley MYP stage with the IM’s shape and propose this approach (named Spikelet Stop) for MYP staging. Following this approach, we compared the MYP stage and the MYP in 27 two- and six-rowed barley accessions grown in the greenhouse and field. Our results reveal that the MYP stage can be reached at various developmental stages, which majorly depend on the genotype and growth conditions. Furthermore, we found that two-rowed barleys’ MYP and the duration reaching the MYP stage may determine their yield potential. Based on our findings, we suggest key steps for the identification of the MYP in barley that can also be applied in a related crop such as wheat.HighlightWe show that the maximum yield potential stage in barley can be different from the awn primordium stage as proposed in earlier studies and it varies depending on the genotype and growth conditions. We suggest key steps to identify maximum yield potential in barley that might apply to related cereals.
A model of the appearance of the moving human eye
Authors: Aguirre Geoffrey K 
Published: February 2021

AbstractThe entrance pupil and first Purkinje reflection (“glint”) in an image of the human eye serve as important features in 3D, model-based eye tracking applications. Here I present a physically and biologically accurate, ray-traced model that supplies the appearance of the pupil and glint of a moving eye. Once biometrically calibrated for a subject under study, simultaneous fitting of the pupil and glint features by the model supplies eye rotation, radius of the aperture stop, and the translation of the eye relative to the initial camera position. The biometric parameters of the model, including corneal curvature and the depth of the centers of rotation, are obtained by model-based fitting of images of the eye posed at known gaze angles. This approach was applied to eye recordings from 30 people obtained during gaze calibration, and while head position was recorded simultaneously using echoplanar magnetic resonance imaging. The refractive and reflective effects of spectacle and contact lenses worn by some subjects were incorporated into the model. The fitted parameters reveal that the center of rotation for horizontal eye movements is deeper (13.8 mm) than that for vertical eye movements (12.1) mm, consistent with prior studies. Individual differences in the depth of the rotation centers, and in corneal curvature, were well related to biometric measures obtained from these subjects using clinical ophthalmologic instruments. Once biometrically calibrated for each subject, gaze position was modeled with a cross-validated, median (across subject) absolute error of 0.58°, and image-plane translation of the head was estimated with sub-millimeter accuracy. The open-source model described here produces biologically accurate simulations of the appearance of the eye in motion, and may be used in model-based search to derive eye pose and biometric properties from empirical data.
Balanced Input from the tRNA Prenyltransferase MiaA Controls the Stress Resistance and Virulence Potential of Extraintestinal PathogenicEscherichia coli
Authors: Blango Matthew G. , Fleming Brittany A. , Kincannon William M. , Tran Alex , Lewis Adam J. , Russell Colin W. , Zhou Qin , Baird Lisa M. , Brannon John R. , Beebout Connor J. , Bandarian Vahe , Hadjifraniskou Maria , Howard Michael T. , Mulvey Matthew A. 
Published: February 2021

ABSTRACTAn ability to adapt to rapidly changing and often hostile environments is key to the success of many bacterial pathogens. InEscherichia coli, the highly conserved enzymes MiaA and MiaB mediate the sequential prenylation and methylthiolation of adenosine-37 within tRNAs that decode UNN codons. Here, we show that MiaA, but not MiaB, is critical to the fitness and virulence of extraintestinal pathogenicE. coli(ExPEC), a major cause of urinary tract and bloodstream infections. Deletion ofmiaAhas pleiotropic effects, rendering ExPEC especially sensitive to stressors like nitrogen and oxygen radicals and osmotic shock. We find that stress can stimulate striking changes inmiaAexpression, which in turn can increase translational frameshifting and markedly alter the bacterial proteome. Cumulatively, these data indicate that ExPEC, and likely other organisms, can vary MiaA levels as a means to fine-tune translation and the spectrum of expressed proteins in response to changing environmental challenges.
The structural and electrophysiological properties of progesterone receptor expressing neurons vary along the anterior-posterior axis of the ventromedial hypothalamus and undergo local changes across the reproductive cycle
Authors: Dias Inês C. , Gutierrez-Castellanos Nicolas , Ferreira Liliana , Lima Susana Q. 
Published: February 2021

AbstractSex hormone levels continuously fluctuate across the reproductive cycle, changing the activity of neuronal circuits to coordinate female behavior and reproductive capacity. The ventrolateral division of the ventromedial hypothalamus (VMHvl) contains neurons expressing receptors for sex hormones and its function is intimately linked to female sexual receptivity. However, recent findings suggest that the VMHvl is functionally heterogeneous. Here, we used whole cell recordings and intracellular labeling to characterize the electrophysiological and morphological properties of individual VMHvl neurons in naturally cycling females. We found that the properties of progesterone receptor expressing (PR+) neurons, but not PR- neurons, depended systematically on the neuron’s location along the anterior-posterior axis of the VMHvl and the phase within the reproductive cycle. Prominent amongst this, the resting membrane potential of anterior PR+ neurons decreased during the receptive phase, while the excitability of medial PR+ neurons increased during the non-receptive phase. During the receptive phase of the cycle, posterior PR+ neurons simultaneously showed an increase in dendritic complexity and a decrease in spine density. These findings reveal an extensive diversity of local rules driving structural and physiological changes in response to fluctuating levels of sex hormones, supporting the anatomical and functional subdivision of the VMHvl and its possible role in the orchestration of different aspects of female socio-sexual behavior.
A novel vascular endothelial growth factor-trap KP-VR2 with enhanced ligand blocking
Authors: Kim Mi-Ra , kim Bongkyu , Na Yunsu , Yoo Jingon , Kim Se-Ho , Seo In-Ra 
Published: February 2021

AbstractAntiangiogenic therapies targeting vascular endothelial growth factor (VEGF)-A have been commonly used in clinics to treat cancers over the past decade. However, their clinical efficacy has been limited, with drawbacks including the acquisition of resistance and activation of compensatory pathways resulting from elevated circulating VEGF-B and placental growth factor (PlGF) levels. Thus, we developed a novel VEGF-Trap, KP-VR2, which can neutralize VEGF-A, VEGF-B, and PlGF to mediate these problems. KP-VR2 consists of two consecutive second Ig-like domains (D2s) of VEGF receptor 1 (VEGFR-1) fused to human IgG1 Fc. KP-VR2 showed more potent decoy activity than the current VEGF-Trap against VEGF and PlGF. Most importantly, two consecutive D2s of VEGFR-1 can generate two putative binding sites, resulting in a significant improvement in binding capacity. These advances resulted in stronger antitumor efficacy in implanted tumor models than aflibercept and bevacizumab. Overall, the results of this study highlight KP-VR2 as a promising therapeutic candidate for further clinical drug development.
Alpha oscillations shape sensory representation and perceptual sensitivity
Authors: Zhou Ying Joey , Iemi Luca , Schoffelen Jan-Mathijs , de Lange Floris P. , Haegens Saskia 
Published: February 2021

AbstractAlpha activity (8–14 Hz) is the dominant rhythm in the awake brain, and thought to play an important role in setting the brain’s internal state. Previous work has associated states of decreased alpha power with enhanced neural excitability. However, evidence is mixed on whether and how such excitability enhancement modulates sensory signals of interest versus noise differently, and what, if any, the consequences are for subsequent perception. Here, human subjects (male and female) performed a visual detection task in which we manipulated their decision criteria in a block-wise manner. While our manipulation led to substantial criterion shifts, these shifts were not reflected in pre-stimulus alpha-band changes. Rather, lower pre-stimulus alpha power in occipital-parietal areas improved perceptual sensitivity and enhanced information content decodable from neural activity patterns. Additionally, oscillatory alpha phase immediately before stimulus presentation modulated accuracy. Together, our results suggest that alpha-band dynamics modulate sensory signals of interest more strongly than noise.Significance statementThe internal state of our brain fluctuates, giving rise to variability in perception and action. Neural oscillations, most prominently in the alpha-band, have been suggested to play a role in setting this internal state. Here, we show that ongoing alpha-band activity in occipital-parietal regions predicts the quality of visual information decodable in neural activity patterns, and subsequently human observer’s sensitivity in a visual detection task. Our results provide comprehensive evidence that visual representation is modulated by ongoing alpha-band activity, and advance our understanding on how, when faced with unchanging external stimuli, internal neural fluctuations influence perception and behavior.
Norepinephrine and glucocorticoids modulate chronic unpredictable stress-induced increase in the type 2 CRF and glucocorticoid receptors in brain structures related to the HPA axis activation
Authors: Malta Marilia B , Martins Joelcimar , Novaes Leonardo S , dos Santos Nilton B , Sita Luciane , Camarini Rosana , Scavone Cristoforo , Bittencourt Jackson , Munhoz Carolina D. 
Published: February 2021

AbstractThe stress response is multifactorial and enrolls circuitries to build a coordinated reaction, leading to behavioral, endocrine, and autonomic changes. These changes are mainly related to the hypothalamus-pituitary-adrenal (HPA) axis activation and the organism’s integrity. However, when self-regulation is ineffective, stress becomes harmful and predisposes the organism to pathologies. The chronic unpredictable stress (CUS) is a widely used experimental model since it induces physiological and behavioral changes and better mimics the stressors variability encountered in daily life. Corticotropin-releasing factor (CRF) and glucocorticoid (GCs) are deeply implicated in the CUS-induced physiological and behavioral changes. Nonetheless, the CUS modulation of CRF receptors and GR and the norepinephrine role in extra-hypothalamic brain areas were not well explored. Here, we show that 14-days of CUS induced a long-lasting HPA axis hyperactivity evidenced by plasmatic corticosterone increase and adrenal gland hypertrophy, which was dependent on both GCs and NE release induced by each stress session. CUS also increased CRF2mRNA expression and GR protein levels in fundamental brain structures related to HPA regulation and behavior, such as the lateral septal nucleus intermedia part (LSI), ventromedial hypothalamic nucleus (VMH), and central nucleus of the amygdala (CeA). We also showed that NE participates in the CUS-induced increase in CRF2and GR levels in the LSI, reinforcing thelocus coeruleus(LC) involvement in the HPA axis modulation. Despite the CUS-induced molecular changes in essential areas related to anxiety-like behavior, this phenotype was not observed in CUS animals 24 h after the last stress session.HighlightsCUS persistently increased plasma CORT levels via GCs and NE signaling.CUS persistently increased CRF2mRNA in extra-hypothalamic brain areas.CUS increased GR protein levels in brain regions related to GCs release control.NE and GCs participate in the CUS-induced increase in CRF2and GR levels.LSI could be the brain nucleus that dictates the fine-tuned response of CUS.CUS animals did not present anxiety-like behavior.
Privacy-Preserving Genotype Imputation in a Trusted Execution Environment
Authors: Dokmai Natnatee , Kockan Can , Zhu Kaiyuan , Wang XiaoFeng , Sahinalp S. Cenk , Cho Hyunghoon 
Published: February 2021

AbstractGenotype imputation is an essential tool in genetics research, whereby missing genotypes are inferred based on a panel of reference genomes to enhance the power of downstream analyses. Recently, public imputation servers have been developed to allow researchers to leverage increasingly large-scale and diverse genetic data repositories for imputation. However, privacy concerns associated with uploading one’s genetic data to a third-party server greatly limit the utility of these services. In this paper, we introduce a practical, secure hardware-based solution for a privacy-preserving imputation service, which keeps the input genomes private from the service provider by processing the data only within a Trusted Execution Environment (TEE) offered by the Intel SGX technology. Our solution features SMac, an efficient, side-channel-resilient imputation algorithm designed for Intel SGX, which employs the hidden Markov model (HMM)-based imputation strategy also utilized by a state-of-the-art imputation software Minimac. SMac achieves imputation accuracies virtually identical to those of Minimac and provides protection against known attacks on SGX while maintaining scalability to large datasets. We additionally show the necessity of our strategies for mitigating side-channel risks by identifying vulnerabilities in existing imputation software and controlling their information exposure. Overall, our work provides a guideline for practical and secure implementation of genetic analysis tools in SGX, representing a step toward privacy-preserving analysis services that can facilitate data sharing and accelerate genetics research.†AvailabilityOur software is available athttps://github.com/ndokmai/sgx-genotype-imputation.
Potential global impact of the N501Y mutation on MHC-II presentation and immune escape
Authors: Castro Andrea , Carter Hannah , Zanetti Maurizio 
Published: February 2021

AbstractThe B.1.1.7 SARS-CoV-2 variant, characterized by the N501Y mutation, is rapidly emerging, raising concerns about its effectiveness on natural as well as vaccine-induced adaptive viral immunity at the population level. Since CD4 T cell responses are of critical importance to the antibody response, we examined the global effects of N501Y mutation on MHC-II presentation compared to the N501 wildtype and found poorer presentation across the majority of MHC-II alleles. This suggests that the N501Y mutation may not only diminish binding of antibodies to the RBD but also interfere with their production by weakening the cooperation between T and B cells, facilitating immune escape.
Characterization of novel regulatory modules controlling leaf angle in maize
Authors: Wang Xianglan , Wang Xiaokun , Sun Shilei , Tu Xiaoyu , Lin Kande , Qin Lei , Wang Xingyun , Li Gang , Zhong Silin , Li Pinghua 
Published: February 2021

AbstractLeaf angle is an important agronomic trait determining maize planting density and light penetration into the canopy, and contributes significantly to the yield gain in modern maize hybrids. However, little is known about its molecular mechanism beyond theLiguless1(LG1) andLiguless2(LG2) genes. In this study, we found that transcription factorZmBEH1is targeted by ZmLG2 and regulates the leaf angle formation by influencing the sclerenchyma cells layers on the adaxial side. ZmBEH1 can interact with transcription factor ZmBZR1, whose expression is directly activated by ZmLG1. Both ZmBEH1 and ZmBZR1 bind to the promoter ofZmSCL28, the third transcription factors that influences the leaf angle. Our study demonstrates novel regulatory modules controlling leaf angle, and provides new gene editing targets for creating optimal maize architecture suitable for dense-planting.
DAZL regulates mRNA deadenylation independently of translation in germ cells
Authors: Smith Richard W. P. , Gorgoni Barbara , Johnston Zoë C. , Richardson William A. , Grieve Kelsey M. , Anderson Ross C. , Gray Nicola K. 
Published: February 2021

ABSTRACTAberrant gene expression during gametogenesis is one of the factors underlying infertility, which affects roughly 15% of couples worldwide.Deleted-in-Azoospermia-Like (DAZL),a member of theDAZ-genefamily, encodes an mRNA-specific regulator of translation which is essential for gametogenesis in both sexes. In this study we show that DAZL controls gene expression in oocytes by regulating the length of the mRNA poly(A) tail, a major determinant of temporal and amplitudinal gene regulation in germ cells, in which gene expression is regulated entirely post-transcriptionally. We show that DAZL does not induce polyadenylation but that binding of DAZL efficiently inhibits mRNA deadenylation induced by oocyte maturation. We reveal that this activity depends on DAZL-mediated recruitment of poly(A)-binding protein, PABP, to the mRNA. Although DAZL also activates mRNA translation via PABP recruitment, mechanistic analysis revealed that neither translation nor translational activation are required for DAZL to stabilise the poly(A) tail, suggesting two mutually independent posttranscriptional roles for the DAZL-PABP complex. We show that recruited PABP must maintain its ability to bind RNA, leading to a model in which DAZL recruits PABP and/or stabilises PABP binding to poly(A) thereby preventing access of deadenylases. These results indicate that the role of DAZL in regulating germ-cell mRNA fate is more complex than previously thought and inform on the poorly understood links between mRNA translation and deadenylation, showing that they can be mechanistically separable.
High Throughput Fitness Profiling Reveals Loss Of GacS-GacA Regulation Improves Indigoidine Production InPseudomonas putida
Authors: Eng Thomas , Banerjee Deepanwita , Lau Andrew K. , Bowden Emily , Herbert Robin A. , Trinh Jessica , Prahl Jan-Philip , Deutschbauer Adam , Tanjore Deepti , Mukhopadhyay Aindrila 
Published: February 2021

AbstractPseudomonas putidaKT2440 is an emerging industrial microbe amenable for use with renewable carbon streams including aromatics such aspara-coumarate (pCA). We examined this microbe under common stirred-tank bioreactor parameters with quantitative fitness assays using a pooled transposon library containing nearly all (4,778) non-essential genes. Assessing differential fitness values by monitoring changes in mutant strain abundance over time identified 31 genes with improved fitness in multiple bioreactor-relevant parameters. Twenty-one genes from this subset were reconstructed, including GacA, a signaling protein, TtgB, an ABC transporter, and PP_0063, a lipid A acyltransferase. Twelve deletion strains with roles in varying cellular functions were evaluated for conversion ofpCA, to a heterologous bioproduct, indigoidine. Several mutants, such as the ΔgacAstrain improved both fitness in a bioreactor and showed an 8-fold improvement in indigoidine production (4.5 g/L, 0.29 g/gpCA, 23% MTY) frompCA as the carbon source.