bluuebunny/crossref_metadata_2025_split huggingface dataset:
The sudden emergence of aNeisseria gonorrhoeaestrain with reduced susceptibility to extended-spectrum cephalosporins, Norway
Authors: Osnes Magnus N. , Didelot Xavier , de Korne-Elenbaas Jolinda , Alfsnes Kristian , Brynildsrud Ola B , Syversen Gaute , Nilsen Øivind , de Blasio Birgitte F. , Caugant Dominique A , Eldholm Vegard 
Published: February 2020

AbstractTheNeisseria gonorrhoeaemultilocus sequence type (ST) 7827 emerged in dramatic fashion in Norway in the period 2016-2018. Here, we aim to determine what enabled it to establish and spread so quickly. In Norway, ST-7827 isolates were almost exclusively isolated from men. Phylogeographic analyses demonstrated an Asian origin of the ST with multiple importation events to Europe. The ST was uniformly resistant to fluoroquinolones and associated with reduced susceptibility to both azithromycin and the extended-spectrum cephalosporins (ESC) cefixime and ceftriaxone. We identified additional independent events of acquisition ofpenAandporBalleles in Europe, associated with further reduction in cefixime and ceftriaxone susceptibility, respectively. Transmission of the ST was largely curbed in Norway in 2019, but our results indicate the existence of a reservoir in Europe. The worrisome drug resistance profile and rapid emergence of ST-7827 calls for close monitoring of the situation.
Visual input into theDrosophila melanogastermushroom body
Authors: Li Jinzhi , Mahoney Brennan Dale , Jacob Miles Solomon , Caron Sophie Jeanne Cécile 
Published: February 2020

ABSTRACTThe ability to integrate input from different sensory systems is a fundamental property of many brains. Yet, the patterns of neuronal connectivity that underlie such multisensory integration remain poorly characterized. TheDrosophila melanogastermushroom body — an associative center required for the formation of olfactory and visual memories — is an ideal system to investigate how different sensory channels converge in higher-order brain centers. The neurons connecting the mushroom body to the olfactory system have been described in great detail, but input from other sensory systems remains poorly defined. Here, we use a range of anatomical and genetic techniques to identify two novel types of mushroom body input neuron that connect visual processing centers — namely the lobula and the posterior lateral protocerebrum — to the dorsal accessory calyx of the mushroom body. Together with previous work that described a pathway conveying visual information from the medulla to the ventral accessory calyx of the mushroom body (Vogt et al., 2016), our study defines a second, parallel pathway that is anatomically poised to convey information from the visual system to the dorsal accessory calyx. This connectivity pattern — the segregation of the visual information into two separate pathways — could be a fundamental feature of the neuronal architecture underlying multisensory integration in associative brain centers.
Deep predictive coding accounts for emergence of complex neural response properties along the visual cortical hierarchy
Authors: Dora S. , Bohte S. M. , Pennartz C.M.A. 
Published: February 2020

AbstractPredictive coding provides a computational paradigm for modelling perceptual processing as the construction of representations accounting for causes of sensory inputs. Here, we develop a scalable, deep predictive coding network that is trained using a Hebbian learning rule. Withouta prioriconstraints that would force model neurons to respond like biological neurons, the model exhibits properties similar to those reported in experimental studies. We analyze low- and high-level properties such as orientation selectivity, object selectivity and sparseness of neuronal populations in the model. As reported experimentally, image selectivity increases systematically across ascending areas in the model hierarchy. A further emergent network property is that representations for different object classes become more distinguishable from lower to higher areas. Thus, deep predictive coding networks can be effectively trained using biologically plausible principles and exhibit emergent properties that have been experimentally identified along the visual cortical hierarchy.Significance StatementUnderstanding brain mechanisms of perception requires a computational approach based on neurobiological principles. Many deep learning architectures are trained by supervised learning from large sets of labeled data, whereas biological brains must learn from unlabeled sensory inputs. We developed a Predictive Coding methodology for building scalable networks that mimic deep sensory cortical hierarchies, perform inference on the causes of sensory inputs and are trained by unsupervised, Hebbian learning. The network models are well-behaved in that they faithfully reproduce visual images based on high-level, latent representations. When ascending the sensory hierarchy, we find increasing image selectivity, sparseness and generalizability for object classification. These models show how a complex neuronal phenomenology emerges from biologically plausible, deep networks for unsupervised perceptual representation.
Assessment of different seedling production techniques ofEuterpe edulis
Authors: Regnier Leonardo Lima Pereira , Salatino Maria Luiza Faria 
Published: February 2020

ABSTRACTEuterpe edulisis an endangered species with high importance ecologically and economically. Seedling production seems to be one of the most important alternatives to population recovery. Besides that, the knowledge of seedling production methods’ influence over germination is very restricted. Thus, this study aimed to evaluate the effects of parent populations, germination conditions, and the substrate to commercial seedling production ofE. edulis. Nine thousand seven hundred and thirteen seeds were distributed between the heated water and control, greenhouse and open-field treatments. The parent population presented high differences between most of the germination indexes. Influencing the germination rate, mean germination time and germination speed, but not affecting synchrony and uncertainty indexes. Heated water treatment did not affect any of the studied indexes, presenting a close pattern of germination over time, indicating it is an appropriate method for seedling production. Greenhouse and open-field treatment presented variations at the same indexes affected in the parent population analysis. The most profitable method forE. edulisseed germination was the greenhouse production method, which provided the best indexes results.
Physiological and Metabolic Features of Mice with CRISPR/Cas9-Mediated Loss-of-Function in Growth Hormone-Releasing Hormone
Authors: Icyuz Mert , Fitch Michael P. , Zhang Fang , Challa Anil K. , Sun Liou Y. 
Published: February 2020

AbstractOur previous study demonstrated that the loss of growth hormone releasing hormone (GHRH) results in increased lifespan and improved metabolic homeostasis in the mouse model generated by classical embryonic stem cell based gene-targeting method. In this study, we targeted the GHRH gene using the CRISPR/Cas9 technology to avoid passenger alleles/mutations and performed in-depth physiological and metabolic characterization. In agreement with our previous observation, male and female GHRH-/-mice have significantly reduced body weight and enhanced insulin sensitivity when compared to wild type littermates. Dual-energy X-ray absorptiometry showed that there were significant decreases in lean mass, bone mineral content and density, and a dramatic increase in fat mass of GHRH-/-mice when compared to wild type littermates. Indirect calorimetry measurements including oxygen consumption, carbon dioxide production and energy expenditure were dramatically reduced in GHRH-/-mice compared to wild type mice. Respiratory exchange ratio was significantly lower in GHRH-/-mice during the light cycle, but not during the dark cycle, indicating a circadian related metabolic shift towards fat utilization in the growth hormone deficient mice. The novel CRISPR/Cas9 GHRH-/-mice are exhibiting the consistent and unique physiological and metabolic characteristics, which might mediate the longevity effects of growth hormone deficiency in mice.
Consensus mutagenesis and ancestral reconstruction provide insight into the substrate specificity and evolution of the front-end Δ6-desaturase family
Authors: Li Dongdi , Damry Adam M. , Petrie James R. , Vanhercke Thomas , Singh Surinder P. , Jackson Colin J. 
Published: February 2020

ABSTRACTMarine algae are a major source of omega (ω)-3 long-chain polyunsaturated fatty acids (ω3-LCPUFAs), which are conditionally essential nutrients in humans and a target for industrial production. The biosynthesis of these molecules in marine algae begins with the desaturation of fatty acids by Δ6-desaturases and enzymes from different species display a range of specificities towards ω3 and ω6 LCPUFAs. In the absence of a molecular structure, the structural basis for the variable substrate specificity of Δ6-desaturases is poorly understood. Here we have conducted a consensus mutagenesis and ancestral protein reconstruction-based analysis of the Δ6-desaturase family, focusing on the ω3-specific Δ6-desaturase fromMicromonas pusilla(MpΔ6des) and the bispecific (ω3/ω6) Δ6-desaturase fromOstreococcus tauri(OtΔ6des). Our characterization of consensus amino acid substitutions in MpΔ6des revealed that residues in diverse regions of the protein, such as the N-terminal cytochrome b5 domain, can make important contributions to determining substrate specificity. Ancestral protein reconstruction also suggests that some extant Δ6-desaturases, such as OtΔ6des, could have adapted to different environmental conditions by losing specificity for ω3-LCPUFAs. This dataset provides a map of regions within Δ6-desaturases that contribute to substrate specificity and could facilitate future attempts to engineer these proteins for use in biotechnology.
Large home range scavengers support higher rates of carcass removal
Authors: Gutiérrez-Cánovas Cayetano , Moleón Marcos , Mateo-Tomás Patricia , Olea Pedro P. , Sebastián-González Esther , Sánchez-Zapata José Antonio 
Published: February 2020

AbstractVertebrate scavenger communities vary in species composition across the globe, and include a wide array of species with diverse ecological strategies and life-histories that support essential ecosystem functions, such as carrion removal. While previous studies have mostly focussed on how community aspects such as species richness and composition affect carrion consumption rates, it remains unclear whether this important function of scavengers is better explained by the dominance of key functional traits or niche complementarity as a result of a diverse functional representation.Here, we test three competitive hypotheses to assess if carrion consumption in vertebrate scavenger communities depends on: i) the presence of key dominant traits (functional identity hypothesis), ii) functional diversity that promotes niche complementarity (functional diversity hypothesis), or iii) the accumulation of individuals and species, irrespective of their trait representation (functional equivalence). To explore these hypotheses, we used five study areas in Spain and South Africa, which represent a gradient of scavenger biodiversity, i.e., ranging from communities dominated by facultative scavengers, such as generalists and meso-predators, to those including vultures and large carnivores.Within study areas, traits that characterise obligate scavengers or large carnivores (e.g. mean home range, proportion of social foragers) were positively linked to rapid carrion consumption, while the biomass of functional groups including facultative scavengers were either weakly or negatively associated with carrion consumption.When combining all study areas, higher rates of carrion consumption were related to scavenger communities dominated by species with large home ranges (e.g.Gypsvultures), which was found to be a key trait. In contrast, metrics describing functional diversity (functional dispersion) and functional equivalence (species richness and abundance) had lower predictive power in explaining carrion consumption patterns.Our data support the functional identity hypothesis as a better framework for explaining carrion consumption rates than functional diversity or equivalence. Our findings contribute to understanding the mechanisms sustaining ecosystem functioning in vertebrate communities and reinforce the role of obligate scavengers and large carnivores as keystone species in terrestrial ecosystems.
The Nef protein of the macrophage tropic HIV-1 strain AD8 counteracts human Bst-2/tetherin
Authors: Giese Sebastian , Lawrence Scott P. , Mazzon Michela , Nijmeijer Bernadien M. , Marsh Mark 
Published: February 2020

AbstractBst-2/tetherin inhibits the release of numerous enveloped viruses by physically attaching nascent particles to infected cells during the process of viral budding from the cell surface. Tetherin also restricts human immunodeficiency viruses (HIV), and pandemic main (M) group HIV-1s are thought to exclusively rely on their Vpu proteins to overcome tetherin-mediated restriction of virus release. However, at least one M group HIV-1 strain, the macrophage-tropic primary AD8 isolate, is unable to expressvpudue to a mutation in its translation initiation codon. Here, using primary monocyte-derived macrophages (MDMs), we show that AD8 was able to use its Nef protein to compensate for the absence of Vpu and restore virus release to wild type levels. We demonstrate that HIV-1 AD8 Nef reduces endogenous tetherin levels from the cell surface, physically separating it from the site of viral budding and thus preventing HIV retention. Mechanistically, AD8 Nef enhances l-tetherin internalisation, leading to perinuclear accumulation of the restriction factor. Finally, we show that Nef proteins from other HIV strains also display varying degrees of tetherin antagonism. Overall, this is the first report showing that M group HIV-1s can use an accessory protein other than Vpu to antagonise human tetherin.
Nanobody mediated neutralization reveals an Achilles heel for norovirus
Authors: Koromyslova Anna D. , Devant Jessica Michelle , Kilic Turgay , Sabin Charles D. , Malak Virginie , Hansman Grant S. 
Published: February 2020

ABSTRACTHuman norovirus frequently causes outbreaks of acute gastroenteritis. Although discovered more than five decades ago, antiviral development has, until recently, been hampered by the lack of a reliable human norovirus cell culture system. Nevertheless, a lot of pathogenesis studies were accomplished using murine norovirus (MNV), which can be grown routinely in cell culture. In this study, we analysed a sizeable library of Nanobodies that were raised against the murine norovirus virion with the main purpose of developing Nanobody-based inhibitors. We discovered two types of neutralizing Nanobodies and analysed the inhibition mechanisms using X-ray crystallography, cryo-EM, and cell culture techniques. The first type bound on the top region of the protruding (P) domain. Interestingly, the Nanobody binding region closely overlapped the MNV receptor-binding site and collectively shared numerous P domain-binding residues. In addition, we showed that these Nanobodies competed with the soluble receptor and this action blocked virion attachment to cultured cells. The second type bound at a dimeric interface on the lower side of the P dimer. We discovered that these Nanobodies disrupted a structural change in the capsid associated with binding co-factors (i.e., metal cations/bile acid). Indeed, we found that capsids underwent major conformational changes following addition of Mg2+or Ca2+. Ultimately, these Nanobodies directly obstructed a structural modification reserved for a post-receptor attachment stage. Altogether, our new data show that Nanobody-based inhibition could occur by blocking functional and structural capsid properties.AUTHOR SUMMARYThis research discovered and analysed two different types of MNV neutralizing Nanobodies. The top-binding Nanobodies sterically inhibited the receptor-binding site, whereas the dimeric-binding Nanobodies interfered with a structural modification associated with co-factor binding. Moreover, we found that the capsid contained a number of vulnerable regions that were essential for viral replication. In fact, the capsid appeared to be organized in a state of flux, which could be important for co-factor/receptor binding functions. Blocking these capsid-binding events with Nanobodies directly inhibited essential capsid functions. Moreover, a number of MNV-specific Nanobody binding epitopes were comparable to human norovirus-specific Nanobody inhibitors. Therefore, this additional structural and inhibition information could be further exploited in the development of human norovirus antivirals.
The acetyltransferase Eco1 elicits cohesin dimerization during S phase
Authors: Shi Di , Zhao Shuaijun , Zuo Mei-Qing , Zhang Jingjing , Hou Wenya , Dong Meng-Qiu , Cao Qinhong , Lou Huiqiang 
Published: February 2020

AbstractSister chromatid cohesion is established by Eco1 in S phase. Nevertheless, the exact consequence of Eco1-catalyzed acetylation is unknown, and the cohesive state remains highly controversial. Here we show that self-interactions of cohesin subunits Scc1/Rad21 and Scc3 occur in a DNA replication-coupled manner in both yeast and human. Through cross-linking mass spectrometry and VivosX analysis of purified cohesin, we show that a subpopulation of cohesin may exist as dimers. Importantly, cohesin-cohesin interaction becomes significantly compromised when Eco1 is depleted. On the other hand, deleting either deacetylase Hos1 or Eco1 antagonist Wpl1/Rad61 results in an increase (e.g., from ∼20% to 40%) of cohesin dimers. These findings suggest that cohesin dimerization is controlled by common mechanisms as the cohesion cycle, thus providing an additional layer of regulation for cohesin to execute various functions such as sister chromatid cohesion, DNA repair, gene expression, chromatin looping and high-order organization.Author SummaryCohesin is a ring that tethers sister chromatids since their synthesis during S phase till their separation in anaphase. According to the single-ring model, one ring holds twin sisters. Here we show a conserved cohesin-cohesin interaction from yeast to human. A subpopulation of cohesin is dimerized concomitantly with DNA replication. Cohesin dimerization is dependent on the acetyltransferase Eco1 and counteracted by the anti-establishment factor Wpl1 and deacetylase Hos1. Approximately 20% of cellular cohesin complexes are measured to be dimers, close to the level of Smc3 acetylation by Eco1 in vivo. These findings provide evidence to support the double-ring model in sister chromatid cohesion.
A Novel Performance Metric for Multiclass Subject Invariant Brain Computer Interfaces with Imbalanced Classes
Authors: Sherwood Jesse , Lowe Jesse , Derakhshani Reza 
Published: February 2020

Abstract[Finding suitable common feature sets for use in multiclass subject independent brain-computer interface (BCI) classifiers is problematic due to characteristically large inter-subject variation of electroencephalographic signatures. We propose a wrapper search method using a one versus the rest discrete output classifier. Obtaining and evaluating the quality of feature sets requires the development of appropriate classifier metrics. A one versus the rest classifier must be evaluated by a scalar performance metric that provides feedback for the feature search algorithm. However, the one versus the rest discrete classifier is prone to settling into degenerate states for difficult discrimination problems. The chance of occurrence of degeneracy increases with the number of classes, number of subjects and imbalance between the number of samples in the majority and minority classes. This paper proposes a scalar Quality (Q)-factor to compensate for classifier degeneracy and to improve the convergence of the wrapper search. The Q-factor, calculated from the ratio of sensitivity to specificity of the confusion matrix, is applied as a penalty to the accuracy (1-error rate). This method is successfully applied to a multiclass subject independent BCI using 10 untrained subjects performing 4 motor tasks in conjunction with the Sequential Floating Forward Selection feature search algorithm and Support Vector Machine classifiers.]
The haemodynamics of the human placenta in utero
Authors: Dellschaft Neele S. , Hutchinson George , Shah Simon , Jones Nia W. , Bradley Chris , Leach Lopa , Platt Craig , Bowtell Richard , Gowland Penny A. 
Published: February 2020

AbstractWe have used MRI to provide important new insights into the function of the human placentain utero. We have measured slow net flow and high net oxygenation in the placentain vivo, which are consistent with efficient delivery of oxygen from mother to fetus. Our experimental evidence substantiates previous hypotheses on the effects of spiral artery remodellingin utero, and also indicates rapid venous drainage from the placenta, which is important since the outflow has been largely neglected in the past. Furthermore, beyond Braxton Hicks contractions, which involve the entire uterus, we have identified a new physiological phenomenon, the ‘utero-placental pump’, by which the placenta and underlying uterine wall contract independently of the rest of the uterus, expelling maternal blood from the intervillous space.
Markers of Acute Toxicity in Pancreatic Beta-Cells Exposed to Lethal Doses of the Organochlorine Pollutant DDT Determined by a Proteomic Approach
Authors: Pavlíková Nela , Šrámek Jan , Jelínek Michael , Halada Petr , Kovář Jan 
Published: February 2020

ABSTRACTMany compounds have the potential to harm pancreatic beta-cells; organochlorine pollutants belong to those compounds. In this work, we aimed to find markers of acute toxicity of p,p‘-DDT among proteins expressed in human pancreatic beta-cells NES2Y and visible at 2-D electrophoresis. We exposed NES2Y cells to a lethal dose of p,p‘-DDT (150 μM) for 24 hours and 30 hours and determined changes in protein expression using 2-D electrophoresis. We also stained the cells exposed to p,p‘-DDT to visualize the altered phenotype of the exposed cells. Among proteins with changed expression, we identified proteins involved in ER stress (GRP78, and endoplasmin), mitochondrial proteins (GRP75, ECHM, IDH3A, NDUS1, and NDUS3), proteins with potential to change the cell morphology (EFHD2, TCPA, NDRG1, and ezrin), and some other proteins (HNRPF, HNRH1, K2C8, vimentin, PBDC1, EF2, PCNA, biliverdin reductase, G3BP1, FRIL, and HSP27). These proteins can be used as markers of acute DDT toxicity.