bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative genetics of temperature performance curves ofNeurospora crassa
Authors: Moghadam Neda N. , Sidhu Karendeep , Summanen Pauliina A. M. , Ketola Tarmo , Kronholm Ilkka 
Published: January 2020

AbstractEarth’s temperature is increasing due to anthropogenic CO2emissions; and organisms need either to adapt to higher temperatures, migrate into colder areas, or face extinction. Temperature affects nearly all aspects of an organism’s physiology via its influence on metabolic rate and protein structure, therefore genetic adaptation to increased temperature may be much harder to achieve compared to other abiotic stresses. There is still much to be learned about the evolutionary potential for adaptation to higher temperatures, therefore we studied the quantitative genetics of growth rates in different temperatures that make up the thermal performance curve of the fungal model systemNeurospora crassa. We studied the amount of genetic variation for thermal performance curves and examined possible genetic constraints by estimating theG-matrix. We observed a substantial amount of genetic variation for growth in different temperatures, and most genetic variation was for performance curve elevation. Contrary to common theoretical assumptions, we did not find strong evidence for genetic trade-offs for growth between hotter and colder temperatures. We also simulated short term evolution of thermal performance curves ofN. crassa, and suggest that they can have versatile responses to selection.
Bumblebee worker body size affects new worker production in different resource environments
Authors: Kerr Natalie Z. , Malfi Rosemary L. , Williams Neal M. , Crone Elizabeth E. 
Published: January 2020

ABSTRACTBehavior and organization of social groups is thought to be vital to the functioning of societies, yet the contributions of various roles within social groups have been difficult to quantify. A common approach to quantifying these role-based contributions is evaluating the performance of individuals at conducting certain roles, these studies ignore how these performances might scale up to effects at the population-level. Manipulative experiments are another common approach to determine population-level effects, but they often ignore potential feedbacks associated with these various roles.Here, we evaluate the effects of worker size distribution in bumblebee colonies on worker production, using functional linear models. Functional linear models are a recent correlative technique that has been used to assess lag effects of environmental drivers on plant performance. We demonstrate potential applications of this technique to explore contributions of social animals to ecological phenomenon.We found that the worker size distribution differentially affected new worker production across three resource environments. Specifically, more larger workers had mostly positive effects and more smaller workers had negative effects on worker production. Most of these effects were only detected under low or fluctuating resource environments suggesting that the advantage of colonies with larger-bodied workers becomes more apparent under stressful conditions.We demonstrate the wider ecological application of functional linear models. We highlight the advantages and limitations when considering these models, and how they are a valuable complement to many of these performance-based and manipulative experiments.
Hierarchical complexity of the macro-scale neonatal brain
Authors: Blesa Manuel , Galdi Paola , Cox Simon R. , Sullivan Gemma , Stoye David Q. , Lamb Gillian J. , Quigley Alan J. , Thrippleton Michael J. , Escudero Javier , Bastin Mark E. , Smith Keith M. , Boardman James P. 
Published: January 2020

AbstractThe human adult structural connectome has a rich nodal hierarchy, with highly diverse connectivity patterns aligned to the diverse range of functional specializations in the brain. The emergence of this hierarchical complexity in human development is unknown. Here, we substantiate the hierarchical tiers and hierarchical complexity of brain networks in the newborn period; assess correspondences with hierarchical complexity in adulthood; and investigate the effect of preterm birth, a leading cause of atypical brain development and later neurocognitive impairment, on hierarchical complexity. We report that neonatal and adult structural connectomes are both composed of distinct hierarchical tiers, and that hierarchical complexity is greater in term born neonates than in preterms. This is due to diversity of connectivity patterns of regions within the intermediate tiers, which consist of regions that underlie sensorimotor processing and its integration with cognitive information. For neonates and adults, the highest tier (hub regions) is ordered, rather than complex, with more homogeneous connectivity patterns in structural hubs. This suggests that the brain develops first a more rigid structure in hub regions allowing for the development of greater and more diverse functional specialization in lower level regions, while connectivity underpinning this diversity is dysmature in infants born preterm.
Isolation and complete genome sequencing of Pectobacterium phage Jarilo, representing a novel genus of bacteriophages within the subfamilyAutographivirinae
Authors: Pedersen Julie Stenberg , Carstens Alexander Byth , Djurhuus Amaru Miranda , Kot Witold , Hansen Lars Hestbjerg 
Published: January 2020

AbstractPectobacterium carotovorumis the causative agent of bacterial soft rot on various plant species. The use of phages for plant disease control have gained increased awareness over the past years. We here describe the isolation and characterization of Pectobacterium phage Jarilo, representing a novel genus of bacteriophages within the subfamilyAutographivirinae. Jarilo possesses a double-stranded DNA genome of 40557 bp with a G+C% content of 50.08% and 50 predicted open reading frames (ORFs). Gene synteny and products seem to be somewhat conserved between Pectobacterium phage Jarilo and Enterobacteria phage T7, but limited nucleotide similarity is found between Jarilo and other phages within the subfamilyAutographivirinae.We propose Pectobacterium phage Jarilo as the first member of a new genus of bacteriophages within the subfamilyAutographivirinae.
Expanded Phylogenetic Diversity and Metabolic Flexibility of Microbial Mercury Methylation
Authors: McDaniel Elizabeth A. , Peterson Benjamin , Stevens Sarah L.R. , Tran Patricia Q. , Anantharaman Karthik , McMahon Katherine D. 
Published: January 2020

ABSTRACTMethylmercury is a potent, bioaccumulating neurotoxin that is produced by specific microorganisms by methylation of inorganic mercury released from anthropogenic sources. ThehgcABgenes were recently discovered to be required for microbial methylmercury production in diverse anaerobic bacteria and archaea. However, the full phylogenetic and metabolic diversity of mercury methylating microorganisms has not been fully explored due to the limited number of cultured, experimentally verified methylators and the limitations of primer-based molecular methods. Here, we describe the phylogenetic diversity and metabolic flexibility of putative mercury methylating microorganisms identified byhgcAsequence identity from publicly available isolate genomes and metagenome-assembled genomes (MAGs), as well as novel freshwater MAGs. We demonstrate that putative mercury methylators are much more phylogenetically diverse than previously known, and the distribution ofhgcAis most likely due to several independent horizontal gene transfer events. Identified methylating microorganisms possess diverse metabolic capabilities spanning carbon fixation, sulfate reduction, nitrogen fixation, and metal resistance pathways. Using a metatranscriptomic survey of a thawing permafrost gradient from which we identified 111 putative mercury methylators, we demonstrate that specific methylating populations may contribute tohgcAexpression at different depths. Overall, we provide a framework for illuminating the microbial basis of mercury methylation using genome-resolved metagenomics and metatranscriptomics to identify methylators based uponhgcApresence and describe their putative functions in the environment.IMPORTANCESpecific anaerobic microorganisms among theDeltaproteobacteria, Firmicutes, andEuryarchaeotahave been shown to produce the bioaccumulating neurotoxin methylmercury. Accurately assessing the sources of microbial methylmercury production in the context of phylogenetic identification, metabolic guilds, and activity in the environment is crucial for understanding the constraints and effects of mercury impacted sites. Advances in next-generation sequencing technologies have enabled large-scale, cultivation-independent surveys of diverse and poorly characterized microorganisms of numerous ecosystems. We used genome-resolved metagenomics and metatranscriptomics to highlight the vast phylogenetic and metabolic diversity of putative mercury methylators, and their depth-discrete activities in the environment. This work underscores the importance of using genome-resolved metagenomics to survey specific putative methylating populations of a given mercury-impacted ecosystem.
Progesterone modulates theta oscillations in the frontal-parietal network
Authors: Riddle Justin , Ahn Sangtae , McPherson Trevor , Girdler Susan , Frohlich Flavio 
Published: January 2020

AbstractThe neuroactive metabolites of the steroid hormones progesterone (P4) and testosterone (T) are GABAergic modulators that influence cognitive control, yet the specific effect of P4 and T on brain network activity remains poorly understood. Here, we investigated if a fundamental oscillatory network activity pattern related to cognitive control, frontal midline theta (FMT) oscillations, are modulated by steroids hormones, P4 and T. We measured the concentration P4 and T using salivary enzyme immunoassay and FMT oscillations using high-density electroencephalography (EEG) during the eyes-open resting state in fifty-five healthy female and male participants. Electrical brain activity was analyzed using Morlet wavelet convolution, beamformer source localization, background noise spectral fitting, and phase amplitude coupling analysis. Steroid hormone concentrations and biological sex were used as predictors for scalp and source-estimated theta oscillations and for top-down theta-gamma phase amplitude coupling. Elevated concentrations of P4 predicted increased FMT oscillatory amplitude across both sexes, and no relationship was found with T. The positive correlation with P4 was specific to the frontal-midline electrodes and survived correction for the background noise of the brain. Using source localization, FMT oscillations were localized to the frontal-parietal network. Additionally, theta amplitude within the frontal-parietal network, but not the default mode network, positively correlated with P4 concentration. Finally, P4 concentration correlated with increased coupling between FMT phase and posterior gamma amplitude. Our results suggest that P4 concentration modulates brain activity via upregulation of theta oscillations in the frontal-parietal network and increased top-down control over posterior cortical sites.Significance StatementThe neuroactive metabolites of the steroid hormones progesterone (P4) and testosterone (T) are GABAergic modulators that influence cognitive control, yet the specific effect of P4 and T on brain network activity remains poorly understood. Here, we investigated if a fundamental oscillatory network activity pattern related to cognitive control, frontal midline theta (FMT) oscillations, are modulated by steroids hormones, P4 and T. Our results suggest that P4 concentration modulates brain activity via upregulation of theta oscillations in the frontal-parietal network and increased top-down control over posterior cortical sites.
Impact of DNA sequences in the DNA duplex opening by the Rad4/XPC nucleotide excision repair complex
Authors: Paul Debamita , Mu Hong , Dai Qing , Tavakoli Amirrasoul , He Chuan , Broyde Suse , Min Jung-Hyun 
Published: January 2020

ABSTRACTRad4/XPC is a key DNA damage sensor for nucleotide excision repair (NER) in eukaryotes. Rad4/XPC recognizes diverse bulky lesions by flipping out two lesion-containing nucleotide pairs and inserting a β-hairpin from the BHD3 domain (β-hairpin3) into the DNA duplex. We have previously observed that Rad4 can form the same ‘open’ structure when covalently tethered to a normal DNA sequence containing consecutive C/G’s (CCC/GGG) and that a similar open-like structure can be formed even when the β-hairpin3 is lacking. Here, we report a crystal structure of the Δβ-hairpin3 mutant tethered to a sequence containing alternating C/G’s (CGC/GCG). In contrast to the previous structures, Rad4 bound to CGC/GCG in a 180°-reversed manner, capping the end of the duplex without flipping out the nucleotides. MD simulations showed that CGC/GCG was inherently less ‘openable’ than CCC/GGG and that Rad4 failed to engage with its minor groove, a hallmark of productive binding towards ‘opening’. These results reveal that DNA sequences significantly influence the thermodynamic barrier for DNA opening by Rad4, which may render certain DNA structures/sequences resistant to ‘opening’ despite a long residence time of Rad4. The reverse- mode may indicate unproductive binding for NER whereas the DNA end-binding may hint at Rad4/XPC’s functions beyond NER.
Cyclodextrin polymer coatings resist protein fouling, mammalian cell adhesion, and bacterial attachment
Authors: Learn Greg D. , Lai Emerson J. , von Recum Horst A. 
Published: January 2020

AbstractUndesired attachment of proteins, cells/bacteria, and organisms on material surfaces is problematic in industrial and health care settings. In this study, polymer coatings are synthesized from subunits of cyclodextrin, an additive/excipient found in food/pharmaceutical formulations. These unique polymers, which have been applied mainly towards sustained drug delivery applications, are evaluated in this study for their ability to mitigate non-specific protein adsorption, mammalian cell (NIH/3T3) adhesion, and bacterial cell (Staphylococcus aureus, Escherichia coli) attachment. Effects of cyclodextrin polymer composition, particularly incorporation of nonpolar crosslinks, on material properties and passive anti-biofouling performance are investigated. Results suggest that lightly-crosslinked cyclodextrin polymers possess excellent passive resistance to protein, cell, and bacterial attachment, likely due to the hydrophilic and electrically neutral surface properties of these coatings. At the same time, anti-biofouling performance decreased with increasing crosslink ratios, possibly a reflection of decreased polymer mobility, increased rigidity, and increased hydrophobic character. Cyclodextrin-based materials may be broadly useful as coatings in industrial or medical applications where biofouling-resistant and/or drug-delivering surfaces are required.
Maturation of human induced pluripotent stem cell-derived cardiomyocytes for modeling hypertrophic cardiomyopathy
Authors: Knight Walter E. , Cao Yingqiong , Lin Ying-Hsi , Sparagna Genevieve C. , Bai Betty , Zhao Yuanbiao , Chi Congwu , Du Yanmei , Londono Pilar , Reisz Julie A. , Brown Benjamin C. , Taylor Matthew R. G. , Ambardekar Amrut V , Cleveland Joseph C. , McKinsey Timothy A. , Jeong Mark Y. , Walker Lori A. , Woulfe Kathleen C. , D’Alessandro Angelo , Chatfield Kathryn C. , Xu Hongyan , Bristow Michael R. , Buttrick Peter M. , Song Kunhua 
Published: January 2020

AbstractRationaleHuman induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are a powerful platform for biomedical research. However, they are immature, which is a barrier to modeling adult-onset cardiovascular disease.ObjectiveWe sought to develop a simple method which could drive cultured hiPSC-CMs towards maturity across a number of phenotypes.Methods and resultsCells were cultured in fatty acid-based media and plated on micropatterned surfaces to promote alignment and elongation. These cells display many characteristics of adult human cardiomyocytes, including elongated cell morphology, enhanced maturity of sarcomeric structures, metabolic behavior, and increased myofibril contractile force. Most notably, hiPSC-CMs cultured under optimal maturity-inducing conditions recapitulate the pathological hypertrophy caused by either a pro-hypertrophic agent or genetic mutations.ConclusionsThe more mature hiPSC-CMs produced by the methods described here will serve as a usefulin vitroplatform for characterizing cardiovascular disease.
Biases and Blind-Spots in Genome-Wide CRISPR Knockout Screens
Authors: Dede Merve , Kim Eiru , Hart Traver 
Published: January 2020

AbstractIt is widely accepted that pooled library CRISPR knockout screens offer greater sensitivity and specificity than prior technologies in detecting genes whose disruption leads to fitness defects, a critical step in identifying candidate cancer targets. However, the assumption that CRISPR screens are saturating has been largely untested. Through integrated analysis of screen data in cancer cell lines generated by the Cancer Dependency Map, we show that a typical CRISPR screen has a ∼20% false negative rate, beyond library-specific false negatives previously described. Replicability falls sharply as gene expression decreases, while cancer subtype-specific genes within a tissue show distinct profiles compared to false negatives. Cumulative analyses across tissues suggest only a small number of lineage-specific essential genes and that these genes are highly enriched for transcription factors that define pathways of tissue differentiation. In addition, we show that half of all constitutively-expressed genes are never hits in any CRISPR screen, and that these never-essentials are highly enriched for paralogs. Together these observations strongly suggest that functional buffering masks single knockout phenotypes for a substantial number of genes, describing a major blind spot in CRISPR-based mammalian functional genomics approaches.
Expected impacts of climate change on tree ferns distribution and diversity patterns in subtropical Atlantic Forest
Authors: de Gasper André Luís , Grittz Guilherme Salgado , Russi Carlos Henrique , Schwartz Carlos Eduardo , Rodrigues Arthur Vinicius 
Published: January 2020

ABSTRACTTree ferns are common elements in the Atlantic Forest domain, sometimes reaching more than half of total dominance at forest sites. Just as most groups, climate change might impact the distribution and diversity of tree ferns. To investigate the extent of these impacts in the subtropical Atlantic Rainforest, we measured the changes in species distribution, α- and β-diversity between current climate and future climatic scenarios for 2050. Most tree ferns species tend to lose their distribution area. Hence, species richness tends to decrease in the future, especially in the Rainforest sites. In general, β-diversity tend to not change on the regional scale, but some sites can change its relative singularity in composition. Our results show that climate change can impact distribution and α-diversity of tree ferns, but with no trend to cause homogenization in the tree ferns of the study area. Protected Areas (PAs) in our study region manage to withhold more α-diversity than areas without PAs — the same applies to β-diversity. Our study offers a new light into the effects of climate change in tree ferns by integrating the evaluation of its impacts on distribution, α- and β-diversity in all study areas and inside PAs.
Accumulation of an unprecedented 5′-deoxyadenos-4′-yl radical unmasks the kinetics of the radical-mediated C-C bond formation step in MoaA catalysis
Authors: Pang Haoran , Lilla Edward A. , Zhang Pan , Zhang Du , Shields Thomas P. , Scott Lincoln G. , Yang Weitao , Yokoyama Kenichi 
Published: January 2020

AbstractRadicalS-adenosyl-L-methionine (SAM) enzymes catalyze various free radical-mediated reactions. In these enzymes, the rate-determining SAM cleavage kinetically masks all the subsequent steps. Due to this kinetic masking, detailed mechanistic characterization of radical transformations catalyzed by these enzymes is very difficult. Here, we report a successful kinetic characterization of the radical C-C bond formation catalyzed by a MoaA radical SAM enzyme. MoaA catalyzes an unprecedented 3′,8-cyclization of GTP into 3′,8-cyclo-7,8-dihydro-GTP (3′,8-cH2GTP) during the molybdenum cofactor (Moco) biosynthesis. Through a series of EPR and biochemical characterization, we found that MoaA accumulates a 5′-deoxyadenos-4′-yl radical (5′-dA-C4′•) under the turnover conditions, and forms (4′S)-5′-deoxyadenosine ((4′S)-5′-dA), which is a C-4′ epimer of the naturally occurring (4′R)-5′-dA. Together with kinetic characterizations, these observations revealed the presence of a shunt pathway in which an on-pathway intermediate, GTP C-3′ radical, abstracts H-4′ atom from 5′-dA to transiently generate 5′-dA-C4′• that is subsequently reduced stereospecifically to yield (4′S)-5′-dA. Detailed kinetic characterization of the shunt and the main pathways provided the comprehensive view of MoaA kinetics, and determined the rate of the on-pathway 3′,8-cyclization step as 2.7 ± 0.7 s−1. Together with DFT calculations, this observation suggested that the 3′,8-cyclization is accelerated by 6 ∼ 9 orders of magnitude by MoaA. Potential contributions of the active-site amino acid residues, and their potential relationships with human Moco deficiency disease are discussed. This is the first determination of the magnitude of catalytic rate acceleration by a radical SAM enzyme, and provides the foundation for understanding how radical SAM enzymes achieve highly specific radical catalysis.