bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plastidic Δ6 fatty-acid desaturases with distinctive substrate specificity regulate the pool of c18-pufas in the ancestral picoalgaostreococcus tauri
Authors: Degraeve-Guilbault C. Charlotte , Gomez Rodrigo E. , Lemoigne Cécile. , Pankansem Nattiwong , Morin Soizic , Tuphile Karine , Joubès Jérôme , Jouhet Juliette , Gronnier Julien , Suzuki Iwane , Domergue Frédéric , Corellou Florence 
Published: March 2020

ABSTRACTEukaryotic Δ6-desaturases are microsomal enzymes which balance the synthesis of ω-3 and ω-6 C18-polyunsaturated-fatty-acids (PUFA) accordingly to their specificity. In several microalgae, includingO. tauri, plastidic C18-PUFA are specifically regulated by environmental cues suggesting an autonomous control of Δ6-desaturation of plastidic PUFA. Sequence retrieval fromO. tauridesaturases, highlighted two putative Δ6/Δ8-desaturases sequences clustering, with other microalgal homologs, apart from other characterized Δ-6 desaturases. Their overexpression in heterologous hosts, includingN. benthamianaandSynechocystis, unveiled their Δ6-desaturation activity and plastid localization.O. taurilines overexpressing these Δ6-desaturases no longer adjusted their plastidic C18-PUFA amount under phosphate starvation but didn’t show any obvious physiological alterations. Detailed lipid analyses from the various overexpressing hosts, unravelled that the substrate features involved in the Δ6-desaturase specificity importantly involved the lipid head-group and likely the non-substrate acyl-chain, in addition to the overall preference for the ω-class of the substrate acyl-chain. The most active desaturase displayed a broad range substrate specificity for plastidic lipids and a preference for ω-3 substrates, while the other was selective for ω-6 substrates, phosphatidylglycerol and 16:4-galactolipid species specific to the native host. The distribution of plastidial Δ6-desaturase products in eukaryotic hosts suggested the occurrence of C18-PUFA export from the plastid.One sentence summaryOsteococcus tauri plastidic lipid C18-PUFA remodelling involves two plastid-located cytochrome-b5 fused Δ6-desaturases with distinct preferences for both head-group and acyl-chain.
Hydrogel mechanical properties are more important than osteoinductive growth factors for bone formation with MSC spheroids
Authors: Whitehead Jacklyn , Griffin Katherine H. , Vorwald Charlotte E. , Gionet-Gonzales Marissa , Cinque Serena E. , Leach J. Kent 
Published: March 2020

ABSTRACTMesenchymal stromal cells (MSCs) can promote tissue repair in regenerative medicine, and their therapeutic potential is further enhancedviaspheroid formation. We demonstrated that intraspheroidal presentation of Bone Morphogenetic Protein-2 (BMP-2) on hydroxyapatite (HA) nanoparticles resulted in more spatially uniform MSC osteodifferentiation, providing a method to internally influence spheroid phenotype. Stress relaxation of hydrogels has emerged as a potent stimulus to enhance monodispersed MSC spreading and osteogenic differentiation, but the effect of hydrogel viscoelasticity on MSC spheroids has not been reported. Herein, we describe a materials-based approach to augment the osteogenic potential of entrapped MSC spheroids by leveraging the mechanical properties of alginate hydrogels. Compared to spheroids entrapped in covalently crosslinked, elastic alginate, calcium deposition of MSC spheroids was consistently increased in ionically crosslinked, viscoelastic alginate. We observed significant increases in calcium deposition by MSC spheroids loaded with BMP-2-HA in viscoelastic gels compared to soluble BMP-2, which was higher than all elastic alginate gels. Upon implantation in critically sized calvarial bone defects, we observed enhanced bone formation in all animals treated with viscoelastic hydrogels. Increases in bone formation were evident in viscoelastic gels, regardless of the mode of presentation of BMP-2 (i.e., soluble delivery or HA nanoparticles). These studies demonstrate that the dynamic mechanical properties of viscoelastic alginate are an effective strategy to enhance the therapeutic potential of MSC spheroids for bone formation and repair.
Hierarchical effects of choice-related activity and neural encoding during feature selective attention
Authors: Mohn Jennifer L. , Downer Joshua D. , O’Connor Kevin N. , Johnson Jeffrey S. , Sutter Mitchell L. 
Published: March 2020

AbstractSelective attention is necessary to sift through, form a coherent percept of, and make behavioral decisions on the vast amount of information present in most sensory environments. How and where selective attention is employed in cortex and how this perceptual information then informs the relevant behavioral decisions is still not well understood. Studies probing selective attention and decision making in visual cortex have been enlightening as to how sensory attention might work in that modality; whether or not similar mechanisms are employed in auditory attention is not yet clear. Therefore, we trained rhesus macaques on a feature selective attention task, where they switched between reporting changes in temporal (amplitude modulation, AM) and spectral (carrier bandwidth) features of a broadband noise stimulus. We investigated how the encoding of these features by single neurons in primary (A1) and secondary (lateral belt, ML) auditory cortex were affected by the different attention conditions. We found that neurons in A1 and ML showed mixed-selectivity to the sound and task features. We found no difference in AM encoding between the attention conditions. We found that choice-related activity in both A1 and ML neurons shifts between attentional conditions. This finding suggests that choice-related activity in auditory cortex does not simply reflect motor preparation or action, and supports the relationship between reported choice-related activity and the decision and perceptual process.New & NoteworthyWe recorded from primary and secondary auditory cortex while monkeys performed a non-spatial feature attention task. Both areas exhibited rate-based choice-related activity. The manifestation of choice-related activity was attention-dependent, suggesting that choice-related activity in auditory cortex does not simply reflect arousal or motor influences, but relates to the specific perceptual choice. The lack of temporal-based choice activity is consistent with growing evidence that subcortical, but not cortical, single neurons inform decisions through temporal envelope following.
An empirical examination of sample size effects on population demographic estimates in birds using single nucleotide polymorphism (SNP) data
Authors: McLaughlin Jessica F. , Winker Kevin 
Published: March 2020

AbstractSample size is a critical aspect of study design in population genomics research, yet few empirical studies have examined the impacts of small sample sizes. We used datasets from eight diverging bird lineages to make pairwise comparisons at different levels of taxonomic divergence (populations, subspecies, and species). Our data are from loci linked to ultraconserved elements (UCEs) and our analyses used one SNP per locus. All individuals were genotyped at all loci (McLaughlin et al. 2020). We estimated population demographic parameters (effective population size, migration rate, and time since divergence) in a coalescent framework using Diffusion Approximation for Demographic Inference (δaδi; Gutenkunst et al. 2009), an allele frequency spectrum (AFS) method. Using divergence-with-gene-flow models optimized with full datasets, we subsampled at sequentially smaller sample sizes from full datasets of 6 – 8 diploid individuals per population (with both alleles called) down to 1:1, and then we compared estimates and their changes in accuracy. Accuracy was strongly affected by sample size, with considerable differences among estimated parameters and among lineages. Effective population size parameters (ν) tended to be underestimated at low sample sizes (fewer than 3 diploid individuals per population, or 6:6 haplotypes in coalescent terms). Migration (m) was fairly consistently estimated until ≤ 2 individuals per population, and no consistent trend of over- or underestimation was found in either time since divergence (T) orΘ(4Nrefμ). Lineages that were taxonomically recognized above the population level (subspecies and species pairs; i.e., deeper divergences) tended to have lower variation in scaled root mean square error (SMRSE) of parameter estimation at smaller sample sizes than population-level divergences, and many parameters were estimated accurately down to 3 diploid individuals per population. Shallower divergence levels (i.e., populations) often required at least 5 individuals per population for reliable demographic inferences using this approach. Although divergence levels might be unknown at the outset of study design, our results provide a framework for planning appropriate sampling and for interpreting results if smaller sample sizes must be used.
Bayesian estimation on logarithmic scales as an explanation for spatiotemporal interferences with a tendency of deceleration
Authors: Chen Youguo , Avitt Andrew , Cui Minghui , Peng Chunhua 
Published: March 2020

AbstractSpatial and temporal information processing interfere with each other. Kappa effect is a famous spatiotemporal interference, in which the estimated time between two lights increases as an increase of distance between the lights, showing a tendency of deceleration. A classical model attributes the interference to constant speeds and predicts a linear relation, whereas a slowness model attributes the interference to slow speeds and proposes the tendency is the result of the variance of stimuli locations. The present study developed a logarithmic version of the classical model and asserts that the tendency is the result of the Web-Fechner law. These hypotheses were tested in two time discrimination tasks by manipulating the variance of stimuli locations and distance between stimuli. The results demonstrate that estimated time was not modulated by the variance of stimuli locations, and increased as an increase of distance with a tendency of deceleration. The Bayesian model on logarithmic scales made more accurate behavioral predictions than the linear model; the estimated constant speed of the logarithmic Bayesian model was equal to the absolute threshold of speed; the strength of the Kappa effect positively correlated with the variability of time perception. Findings suggest that the interference in the Kappa effect is driven by slow speeds, the strength of the interference is influenced by the variability of time perception, and the tendency of deceleration is the result of the Weber-Fechner law. This Bayesian framework may be useful when applied in the field of time perception and other types of cross-dimensional interferences.
Isopropoxy benzene guanidine killsStaphylococcus aureuswithout detectable resistance
Authors: Zhang Xiufeng , Peng Xianfeng , Lu Yixing , Hao Jie , Li Fangping , Qin Zonghua , Xiong Wenguang , Zeng Zhenling 
Published: March 2020

AbstractAntibiotic resistance is a serious public health crisis. The challenge caused byStaphylococcus aureusinfections clearly urges the development of novel antimicrobial therapy. Drug repurposing has emerged as an alternative approach to rapidly identify effective drugs against multidrug-resistant bacteria. Recently, substituted benzene guanidine compounds have been used as leading structures to discover new promising drugs in both synthetic and medicinal chemistry. We investigated the antimicrobial activity of an analog of substituted benzene guanidine compounds (isopropoxy benzene guanidine) and further explored its antibacterial mechanism againstS. aureus. Isopropoxy benzene guanidine had a MIC of 0.125-4μg/ml againstS. aureusand displayed potent activity againstS. aureusby disrupting cell membrane. Unlike conventional antibiotics, repeated use of isopropoxy benzene guanidine had a low probability of resistance section. The most substantial isopropoxy benzene guanidine-induced changes occurred in transcript levels of membrane transport functions-regulated genes, and genes involved in purine- and pyrimidine-synthesis pathway and virulence factors. Furthermore,in vivostudies demonstrated that isopropoxy benzene guanidine is capable of treating invasive MRSA infections. These findings provided strong evidence that isopropoxy benzene guanidine represents a new chemical lead for novel antibacterial agent against multidrug-resistantS. aureusinfections.
Weakest link dynamics predict apparent antibiotic interactions in a model cross-feeding community
Authors: Adamowicz Elizabeth M. , Harcombe William R. 
Published: March 2020

AbstractWith the growing global threat of antimicrobial resistance, novel strategies are required for combatting resistant pathogens. Combination therapy, wherein multiple drugs are used to treat an infection, has proven highly successful in the treatment of cancer and HIV. However, this practice has proven challenging for the treatment of bacterial infections due to difficulties in selecting the correct combinations and dosages. An additional challenge in infection treatment is the polymicrobial nature of many infections, which may respond to antibiotics differently than a monoculture pathogen. This study tests whether patterns of antibiotic interactions (synergy, antagonism, or independence/additivity) in monoculture can be used to predict antibiotic interactions in an obligate cross-feeding co-culture. Using our previously described weakest link hypothesis, we hypothesized antibiotic interactions in co-culture based on the interactions we observed in monoculture. We then compared our predictions to observed antibiotic interactions in co-culture. We tested the interactions between ten previously identified antibiotic combinations using checkerboard assays. Although our antibiotic combinations interacted differently than predicted in our monocultures, our monoculture results were generally sufficient to predict co-culture patterns based solely on the weakest link hypothesis. These results suggest that combination therapy for cross-feeding multispecies infections may be successfully designed based on antibiotic interaction patterns for their component species.
Identification ofCandida glabrataTranscriptional Regulators that Govern Stress Resistance and Virulence
Authors: Filler Elan E. , Liu Yaoping , Solis Norma V. , Diaz Luis F. , Edwards John E. , Filler Scott G. , Yeaman Michael R. 
Published: March 2020

AbstractThe mechanisms by whichCandida glabrataresists host defense peptides and caspofungin are incompletely understood. To identify transcriptional regulators that enableC. glabratato withstand these classes of stressors, a library of 215C. glabratatranscriptional regulatory deletion mutants was screened for susceptibility to both protamine and caspofungin. We identified 8 mutants that had increased susceptibility to both host defense peptides and caspofungin. Of these mutants, 6 were deleted for genes that were predicted to specify proteins involved in histone modification. These genes wereADA2, GCN5, SPT8, HOS2, RPD3, andSPP1. Theada2Δ andgcn5Δ mutants also had increased susceptibility to other stressors such as H2O2and SDS. In theGalleria mellonellamodel of disseminated infection, theada2Δ andgcn5Δ mutants had attenuated virulence, whereas in neutropenic mice, the virulence of theada2Δ andrpd3Δ mutants was decreased. Thus, histone modification plays a central role in enablingC. glabratato withstand host defense peptides and caspofungin, and Ada2 is essential for the maximal virulence of this organism during disseminated infection.
Death in Venice: A Digital Reconstruction of a Large Plague Outbreak During 1630-1631
Authors: Lazzari Gianrocco , Colavizza Giovanni , Bortoluzzi Fabio , Drago Davide , Erboso Andrea , Zugno Francesca , Kaplan Frédéric , Salathé Marcel 
Published: March 2020

AbstractThe plague, an infectious disease caused by the bacterium Yersinia pestis, is widely considered to be responsible for the most devastating and deadly pandemics in human history. Starting with the infamous Black Death, plague outbreaks are estimated to have killed around 100 million people over multiple centuries, with local mortality rates as high as 60%. However, detailed pictures of the disease dynamics of these outbreaks centuries ago remain scarce, mainly due to the lack of high-quality historical data in digital form. Here, we present an analysis of the 1630-31 plague outbreak in the city of Venice, using newly collected daily death records. We identify the presence of a two-peak pattern, for which we present two possible explanations based on computational models of disease dynamics. Systematically digitized historical records like the ones presented here promise to enrich our understanding of historical phenomena of enduring importance. This work contributes to the recently renewed interdisciplinary foray into the epidemiological and societal impact of pre-modern epidemics.
Genomic signals of admixture and reinforcement between two closely related species of European sepsid flies
Authors: Giesen Athene , Blanckenhorn Wolf U. , Schäfer Martin A. , Shimizu Kentaro K. , Shimizu-Inatsugi Rie , Misof Bernhard , Niehuis Oliver , Podsiadlowski Lars , Lischer Heidi E. L. , Aeschbacher Simon , Kapun Martin 
Published: March 2020

ABSTRACTInterspecific gene flow by hybridization may weaken species barriers and adaptive divergence, but can also initiate reinforcement of reproductive isolation trough natural and sexual selection. The extent of interspecific gene flow and its consequences for the initiation and maintenance of species barriers in natural systems remain poorly understood, however. To assess genome-wide patterns of gene flow between the two closely related European dung fly speciesSepsis cynipseaandSepsis neocynipsea(Diptera: Sepsidae), we tested for historical gene flow with the aid of ABBA-BABA test using whole-genome resequencing data from pooled DNA of male specimens originating from natural and laboratory populations. We contrasted genome-wide variation in DNA sequence differences between samples from sympatric populations of the two species in France and Switzerland with that of interspecific differences between pairs of samples involving allopatric populations from Estonia and Italy. In the French Cevennes, we detected a relative excess of DNA sequence identity, suggesting interspecific gene flow in sympatry. In contrast, at two sites in Switzerland, we observed a relative depletion of DNA sequence identity compatible with reinforcement of species boundaries in sympatry. Our results suggest that the species boundaries betweenS. cynipseaandS. neocynipseain Europe depend on the eco-geographic context.
Lipids as currency in ecological interactions: Competition and facilitation between two lipid scavenging parasitoids
Authors: Lammers Mark , van Gorkum Tim A. M. , Hoeijmans Stefanie , Kraaijeveld Ken , Harvey Jeffrey A. , Ellers Jacintha 
Published: March 2020

AbstractInterspecific interactions in nature often revolve around the acquisition of nutrients. Depending on the organisms’ metabolic requirements, competition for specific essential nutrients may occur, which selects for increased abilities to monopolize, consume and store these nutrients. Lipid scavengers are organisms that rely on exogenous lipid acquisition as they lack the ability to synthesize fatty acidsde novoor in sufficient quantity. Most parasitoid insects are lipid scavengers: they obtain all required lipids by feeding on their hosts as larvae. Here we study the nutritional ecology of competitive interactions between nativeNasonia vitripennisand introducedTachinaephagus zealandicus. While the former was already known to lack lipogenesis, we show thatT. zealandicusalso relies on host lipids. The interactions between the two species were studied using competition experiments, in which oviposition ofT. zealandicuson a host was followed by multiparasitism byN. vitripennis. The outcome of competition was determined by the duration of the time lag between oviposition events.N. vitripenniswas superior when arriving 3 days after oviposition byT. zealandicus. In contrast, 9 days after oviposition ofT. zealandicuswe observed complete reversal, and noN. vitripennisoffspring were able to develop. Only whenN. vitripennislaid eggs 15 days afterT. zealandicusoviposition, both species could emerge from the same host. However,N. vitripennisrealizes only 10% of its potential fitness at this time point because prior parasitization by the gregariousT. zealandicuscompartmentalizes the host resources, limiting the spread ofN. vitripennis’venom. This study shows that successful reproduction ofN. vitripennisat 15 days was achieved by hyperparasitizing, a capability that provides a fitness benefit toN. vitripennis, as it extends the time window that hosts are available for parasitization. Choice tests with hosts at different time intervals afterT. zealandicusoviposition revealed a partial mismatch inN. vitripennisfemales between competition avoidance and offspring performance, which may be linked to the limited co-evolutionary time between native and introduced species. We discuss our results in the context of nutritional ecology and, specifically, the role of lipids in ecological interactions.
Replacing the Calvin cycle with the reductive glycine pathway inCupriavidus necator
Authors: Claassens Nico J. , Bordanaba-Florit Guillermo , Cotton Charles A. R. , De Maria Alberto , Finger-Bou Max , Friedeheim Lukas , Giner-Laguarda Natalia , Munar-Palmer Martí , Newell William , Scarinci Giovanni , Verbunt Jari , de Vries Stijn T. , Yilmaz Suzan , Bar-Even Arren 
Published: March 2020

AbstractFormate can be directly produced from CO2and renewable electricity, making it a promising microbial feedstock for sustainable bioproduction.Cupriavidus necatoris one of the few biotechnologically-relevant hosts that can grow on formate, but it uses the inefficient Calvin cycle. Here, we redesignC. necatormetabolism for formate assimilation via the highly efficient synthetic reductive glycine pathway. First, we demonstrate that the upper pathway segment supports glycine biosynthesis from formate. Next, we explore the endogenous route for glycine assimilation and discover a wasteful oxidation-dependent pathway. By integrating glycine biosynthesis and assimilation we are able to replaceC. necator’s Calvin cycle with the synthetic pathway and achieve formatotrophic growth. We then engineer more efficient glycine metabolism and use short-term evolution to optimize pathway activity, doubling the growth yield on formate and quadrupling the growth rate. This study thus paves the way towards an ideal microbial platform for realizing the formate bioeconomy.