bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatial arrangement drastically changes the neural representation of multiple visual stimuli that compete in more than one feature domain
Authors: Wiesner Steven , Baumgart Ian W. , Huang Xin 
Published: July 2019

ABSTRACTNatural scenes often contain multiple objects and surfaces. However, how neurons in the visual cortex represent multiple visual stimuli is not well understood. Previous studies have shown that, when multiple stimuli compete in one feature domain, the evoked neuronal response is biased toward the stimulus that has a stronger signal strength. Here we investigate how neurons in the middle temporal (MT) cortex of macaques represent multiple stimuli that compete in more than one feature domain. Visual stimuli were two random-dot patches moving in different directions. One stimulus had low luminance contrast and moved with high coherence, whereas the other had high contrast and moved with low coherence. We found that how MT neurons represent multiple stimuli depended on the spatial arrangement of the stimuli. When two stimuli were overlapping, MT responses were dominated by the stimulus component that had high contrast. When two stimuli were spatially separated within the receptive fields, the contrast dominance was abolished. We found the same results when using contrast to compete with motion speed. Our neural data and computer simulations using a V1-MT model suggest that the contrast dominance found with overlapping stimuli is due to normalization occurring at an input stage fed to MT, and MT neurons cannot overturn this bias based on their own feature selectivity. The interaction between spatially separated stimuli can largely be explained by normalization within MT. Our results revealed new rules on stimulus competition and highlighted the impact of hierarchical processing on representing multiple stimuli in the visual cortex.SIGNIFICANCE STATEMENTPrevious studies have shown that the neural representation of multiple visual stimuli can be accounted for by a divisive normalization model. By using multiple stimuli that compete in more than one feature domain, we found that luminance contrast has a dominant effect in determining competition between multiple stimuli when they were overlapping but not spatially separated. Our results revealed that neuronal responses to multiple stimuli in a given cortical area cannot be simply predicted by the population neural responses elicited in that area by the individual stimulus components. To understand the neural representation of multiple stimuli, rather than considering response normalization only within the area of interest, one must consider the computations including normalization occurring along the hierarchical visual pathway.
The YdiU Domain Modulates Bacterial Stress Signaling through Mn2+-dependent UMPylation
Authors: Yang Yinlong , Yue Yingying , Song Nannan , Li Cuiling , Yuan Zenglin , Wang Yan , Ma Yue , Li Hui , Zhang Fengyu , Wang Weiwei , Jia Haihong , Li Peng , Li Xiaobing , Wang Qi , Ding Zhe , Dong Hongjie , Gu Lichuan , Li Bingqing 
Published: July 2019

SUMMARYSensing stressful conditions and adjusting cellular metabolism to adapt to the environment is essential for bacteria to survive in variable situations. Here, we describe a new stress-related protein YdiU, and characterize YdiU as an enzyme that catalyzes the covalent attachment of uridine 5’-monophosphate to a protein tyrosine/histidine residue—a novel modification defined as UMPylation. Mn2+serves as an essential co-factor for YdiU-mediated UMPylation. UTP and Mn2+-binding converts YdiU to an aggregate-prone state facilitating the recruitment of chaperones. The UMPylation of chaperones prevents them from binding co-factors or clients, thereby impairing their function. Consistent with the recent finding that YdiU acts as an AMPylator, we further demonstrate that the self-AMPylation of YdiU padlocks its chaperone-UMPylation activity. The detailed mechanism is proposed based on Apo-YdiU, YdiU-ATP, YdiU-AMP crystal structures and molecular dynamics simulation models of YdiU-UTP and YdiU-UTP-peptide.In vivodata demonstrate that YdiU effectively protectsSalmonellafrom stress-induced ATP depletion through UMPylation.HighlightsYdiU involves in stress-resistance ofSalmonella.YdiU mediates protein UMPylation in a Mn2+-dependent manner.Structural insights into YdiU-mediated UMPylation.UMPylation of chaperones by YdiU modulates their function.
Long-read assembly of the Chinese rhesus macaque genome and identification of ape-specific structural variants
Authors: He Yaoxi , Luo Xin , Zhou Bin , Hu Ting , Meng Xiaoyu , Audano Peter A. , Kronenberg Zev N. , Eichler Evan E. , Jin Jie , Guo Yongbo , Yang Yanan , Qi Xuebin , Su Bing 
Published: July 2019

AbstractRhesus macaque (Macaca mulatta) is a widely-studied nonhuman primate. Here we present a high-quality de novo genome assembly of the Chinese rhesus macaque (rheMacS) using long-read sequencing and multiplatform scaffolding approaches. Compared to the current Indian rhesus macaque reference genome (rheMac8), the rheMacS genome assembly improves sequence contiguity by 75-fold, closing 21,940 of the remaining assembly gaps (60.8 Mbp). To improve gene annotation, we generated more than two million full-length transcripts from ten different tissues by long-read RNA sequencing. We sequence resolve 53,916 structural variants (96% novel) and identify 17,000 ape-specific structural variants (ASSVs) based on comparison to the long-read assembly of ape genomes. We show that many ASSVs map within ChIP-seq predicted enhancer regions where apes and macaque show diverged enhancer activity and gene expression. We further characterize a set of candidate ASSVs that may contribute to ape- or great-ape-specific phenotypic traits, including taillessness, brain volume expansion, improved manual dexterity, and large body size. This improved rheMacS genome assembly serves as an ideal reference for future biomedical and evolutionary studies.
Mutations in a single signaling pathway allow growth on a different solvent than water
Authors: Kampmeyer Caroline , Johansen Jens V. , Holmberg Christian , Karlson Magnus , Gersing Sarah K. , Bordallo Heloisa N. , Kragelund Birthe B. , Lerche Mathilde H. , Jourdain Isabelle , Winther Jakob R. , Hartmann-Petersen Rasmus 
Published: July 2019

AbstractSince life is completely dependent on water, it is difficult to gauge the impact of solvent change. To analyze the role of water as a solvent in biology, we replaced water with heavy water (D2O), and investigated the biological effects by a wide range of techniques, using the fission yeastSchizosaccharomyces pombeas model organism. We show that high concentrations of D2O lead to altered glucose metabolism, growth retardation, and inhibition of meiosis. However, mitosis and overall cell viability were only slightly affected. After prolonged incubation in D2O, cells displayed gross morphological changes, thickened cell walls as well as aberrant septa and cytoskeletal organization. RNA sequencing revealed that D2O causes a strong downregulation of most tRNAs and triggers activation of the general stress response pathway. Genetic screens identified several D2O sensitive mutants, while mutants compromised in the cell integrity pathway, including the protein kinase genespmk1,mkh1,pek1andpck2, that control cell wall biogenesis, were more tolerant to D2O. We speculate that D2O affects the phospholipid membrane or cell wall glycans causing an activation of the cell integrity pathway. In conclusion, the effects of solvent replacement are pleiotropic but the D2O-triggered activation of the cell integrity pathway and subsequent increased deposition of cell wall material and septation problems appear most critical for the cell growth defects.
PAWER: Protein Array Web ExploreR
Authors: Fishman Dmytro , Kuzmin Ivan , Adler Priit , Vilo Jaak , Peterson Hedi 
Published: July 2019

AbstractProtein microarray is a well-established approach for characterizing activity levels of thousands of proteins in a parallel manner. Analysis of protein microarray data is complex and time-consuming, while existing solutions are either outdated or challenging to use without programming skills. The typical data analysis pipeline consists of a data preprocessing step, followed by differential expression analysis, which is then put into context via functional enrichment. Normally, biologists would need to assemble their own workflow by combining a set of unrelated tools to analyze experimental data. Provided that most of these tools are developed independently by various bioinformatics groups, making them work together could be a real challenge. Here we present PAWER, the first online tool for protein microarray analysis. PAWER enables biologists to carry out all the necessary analysis steps in one go. PAWER provides access to state-of-the-art computational methods through a user-friendly interface, resulting in publication-ready illustrations. We also provide an R package for more advanced use cases, such as bespoke analysis workflows. PAWER is freely available at https://biit.cs.ut.ee/pawer.
Multistage activity within a diverse set of epi-drugs against Plasmodium falciparum parasites
Authors: Coetzee Nanika , von Grüning Hilde , van der Watt Mariette , Reader Janette , Birkholtz Lyn-Marié 
Published: July 2019

AbstractThe epigenome of the malaria parasite, Plasmodium falciparum, is associated with control of various essential processes in the parasite including control of proliferation of asexual development as well as sexual differentiation. The unusual nature of the epigenome has prompted investigations of the potential to target epigenetic modulators with novel chemotypes. Here, we explored the diversity associated with a library of 95 compounds, active against various epigenetic modifiers within cancerous cells, for activity against multiple stages of P. falciparum development. We show that P. falciparum is differentially susceptible to epigenetic perturbation during asexual and sexual development, with early stage gametocytes particularly sensitive to epi-drugs targeting both histone and non-histone epigenetic modifiers. Moreover, 4 compounds targeting histone acetylation and methylation, show potent multistage activity against asexual parasites, early and late stage gametocytes, with transmission-blocking potential. Overall, these results warrant further examination of the potential antimalarial properties of these hit compounds.
A rhomboid protease, EhROM1, regulates the submembrane distribution and size of the Gal/GalNAc lectin subunits in the human protozoan parasite, Entamoeba histolytica
Authors: Welter Brenda H. , Temesvari Lesly A. 
Published: July 2019

AbstractEntamoeba histolytica is a food- and waterborne parasite that is the causative agent of amebic dysentery and amoebic liver abscesses. Adhesion is one of the most important virulence functions as it facilitates motility, colonization of host, destruction of host tissue, and uptake of nutrients by the parasite. One well-characterized parasite cell surface adhesin is the Gal/GalNAc lectin, which binds to galactose or N-acetylgalactosamine residues on host components and is composed of heavy (Hgl), intermediate (Igl), and light (Lgl) subunits. Igl has been shown to be constitutively localized to lipid rafts (cholesterol-rich membrane domains), whereas Hgl and Lgl transiently associate with rafts. When all three subunits are localized to rafts there is an increase in galactose-sensitive adhesion. Thus, submembrane location may regulate the function of this adhesion. Rhomboid proteases are a conserved family of intramembrane proteases that also participate in the regulation of parasite-host interactions. In E. histolytica, one rhomboid protease, EhROM1, cleaves Hgl as a substrate, and knockdown of its expression inhibits parasite-host interactions. Since rhomboid proteases are found within membranes, it is not surprising that lipid composition regulates their activity and enzyme-substrate binding. Given the importance of the lipid environment for both rhomboid proteases and the Gal/GalNAc lectin, we sought to gain insight into the relationship between rhomboid proteases and submembrane location of the lectin in E. histolytica. We demonstrated that EhROM1, itself, is enriched in rafts. Reducing rhomboid protease activity, either pharmacologically or genetically, correlated with an enrichment of Hgl and Lgl in rafts. In a mutant cell line with reduced EhROM1 expression, there was also a significant augmentation of the level of all three Gal/GalNAc subunits on the cell surface and an increase in the molecular weight of Hgl and Lgl. Overall, the study provides insight into the molecular mechanisms governing parasite-host adhesion for this pathogen.
Associated factors and spatial patterns of the epidemic sporotrichosis in a high density human populated area: A cross-sectional study from 2016 to 2018
Authors: Lecca Lívian Otávio , Paiva Marcelo Teixeira , Stefanie Fonseca de Oliveira Camila , Franco Morais Maria Helena , de Azevedo Maria Isabel , de Valgas e Bastos Camila , Keller Kelly Moura , Ecco Roselene , Silva Alves Márcia Regina , Tavares Pais Graziella Coelho , Salvato Lauranne Alves , de Morais Donancio Xaulim Gustavo , Barbosa David Soeiro , Brandão Silvana Tecles , Ferreira de Magalhães Soares Danielle 
Published: July 2019

AbstractWe carried out an epidemiological characterization of human and feline sporotrichosis, between 2016 and 2018, in a high density-populated area in Brazil. Professionals were trained to identify suspected cats and notified vets to interview the owners and collect swabs of the wounds from these animals. Mycological cultures were performed, and colonies identified for Spotrothrix spp. Subsequently, data regarding the outcome from suspected animals were collected. Confirmed cases of human sporotrichosis (56) were also counted and analysed for spatial distribution. Regions with highest prevalence of feline sporotrichosis, had greater frequencies of both human and feline cases. 118 (77.63%) animals were positive. Animals that lived only partially at home were 3.02 times more likely of being positive (OR 3.02, CI 95% 1,96-10,43). The prevalence of feline sporotrichosis was 8.36 ‰ (CI 95%, 5.38 - 9.55 ‰). There was no statistically significant association between environmental variables and positive diagnosis, corroborating the hypothesis that direct transmission by infected cats plays a greater role in the occurrence and continuous outbreaks of sporotrichosis in Brazil. Among the positive animals, 61.90% (CI 95% 58.95 - 64.96) died, being 6.30 times more likely to die than negative animals (p< 0.05, OR 6.30, CI 95% 2,79-14,42). The lethality rate was 55.08% in cats (CI 95% 49.20 - 51.15). The mortality for sporotrichosis was 4.6 ‰ cats (CI 95% 3.4 - 6 ‰). Only 7.62% (CI 95% 7.12 - 8.16) positive cats were treated and cured. Among dead positive animals, 29.23% were inappropriately discarded. This is the first report on the epidemic of sporotrichosis in Minas Gerais, Brazil. The free offer for treatment and veterinary care to these animals should be taken into consideration, as well as the collection and incineration of the dead ones, as measures of public health, followed by the guidance and care for the human patient.
Lower limb chronic edema management program: Perspectives of disengaged patients on challenges, enablers and barriers to program attendance and adherence
Authors: Khong Linda A. M. , Buckley Amma , Johnson Wendy , Cavalheri Vinicius 
Published: July 2019

AbstractBackgroundChronic edema (CO) is a progressive, physically disfiguring and currently incurable condition. A multifaceted program has been recommended to manage the swelling. However, there is little evidence investigating patients’ perspectives following the program, particularly for those who have poor adherence or are disengaged.AimTo investigate the perceived challenges faced by disengaged participants with lower limb CO by identifying their enablers and barriers to participating in a Physiotherapy CO program.MethodAn exploratory qualitative approach was used. A purposive sampling strategy was adopted to recruit participants. Those with more than three months swelling and who had low adherence or attendance (disengaged) to the CO program were invited to participate. Semi-structured interviews with six participants from a CO clinic in a tertiary hospital were conducted. Data was thematically analyzed and findings in terms of enablers and barriers were subsequently reflected in the light of a theoretical framework.ResultsAll six participants were morbidly obese (BMI 47 ± 4 kg/m2) with multiple chronic comorbidities. Enablers and barriers detected included physical, psychological and social factors that interplay to present multidimensional challenges that influence the participants’ adjustment to managing their CO. For the disengaged participants in this study, their under-managed lower limb CO was a progression towards being housebound and having a gradually increasing level of disability.ConclusionChronic edema, if left unmanaged, can have a profound debilitating impact on the individual permanently. Understanding the challenges faced by patients with lower limb CO has implications for developing a more patient-centered multidisciplinary approach to clinical practice and suggests the need for further research.
Tobacco Hornworm (Manduca sexta) caterpillars as a novel host model for the study of fungal virulence and drug efficacy
Authors: Lyons Naomi , Softley Isabel , Balfour Andrew , Williamson Carolyn , O’Brien Heath E. , Shetty Amol C. , Bruno Vincent M. , Diezmann Stephanie 
Published: July 2019

AbstractThe two leading yeast pathogens of humans, Candida albicans and Cryptococcus neoformans, cause systemic infections in >1.4 million patients world-wide with mortality rates approaching 75%. It is thus imperative to study fungal virulence mechanisms, efficacy of antifungal drugs, and host response pathways. While this is commonly done in mammalian models, which are afflicted by ethical and practical concerns, invertebrate models, such as wax moth larvae and nematodes have been introduced over the last two decades. To complement existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca sexta as a novel host model. These caterpillars can be maintained at 37°C, are suitable for injections with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including C. albicans, C. neoformans, C. auris, and C. glabrata. Importantly, fungal burden can be assessed daily throughout the course of infection in a single caterpillar’s faeces and haemolymph. Infected caterpillars can be rescued by treatment with antifungal drugs. Notably, these animals are large enough for weight to provide a reliable and reproducible measure of fungal disease. M. sexta caterpillars combine a suite of parameters that make them suitable for the study of fungal virulence.
Evidence for a unitary structure of spatial cognition beyond general intelligence
Authors: Malanchini Margherita , Rimfeld Kaili , Shakeshaft Nicholas G. , McMillan Andrew , Schofield Kerry L. , Rodic Maja , Rossi Valerio , Kovas Yulia , Dale Philip S. , Tucker-Drob Elliot M. , Plomin Robert 
Published: July 2019

ABSTRACTPerformance in everyday spatial orientation tasks (e.g. map reading and navigation) has been considered functionally separate from performance on more abstract object-based spatial abilities (e.g. mental rotation and visualization). However, evidence remains scarce and unsystematic. With a novel gamified battery, we assessed six tests of spatial orientation in a virtual environment and examined their association with ten object-based spatial tests, as well as their links to general cognitive ability (g). We further estimated the role of genetic and environmental factors in underlying variation and covariation in these spatial tests. Participants (N = 2,660) were part of the Twins Early Development Study, aged 19 to 22. The 6 tests of spatial orientation clustered into a single ‘Navigation’ factor that was 64% heritable. Examining the structure of spatial ability across all 16 tests, three factors emerged: Navigation, Object Manipulation and Visualization. These, in turn, loaded strongly onto a general factor of Spatial Ability, which was highly heritable (84%). A large portion (45%) of this high heritability was independent of g. The results from this most comprehensive investigation of spatial abilities to date point towards the existence of a common genetic network that supports all spatial abilities.
Interferon-stimulated genes in zebrafish and human define an ancient arsenal of antiviral immunity
Authors: Levraud Jean-Pierre , Jouneau Luc , Briolat Valérie , Laghi Valerio , Boudinot Pierre 
Published: July 2019

AbstractThe evolution of the interferon (IFN) system, the major innate antiviral mechanism of vertebrates, remains poorly understood. According to the detection of type I IFN genes in cartilaginous fish genomes, the system appeared 500My ago. However, the IFN system integrates many other components, most of which are encoded by IFN-stimulated genes (ISGs). To shed light on its evolution, we have used deep RNA sequencing to generate a comprehensive list of ISGs of zebrafish, taking advantage of the high quality genome annotation in this species. We analyzed larvae after inoculation of recombinant zebrafish type I IFN, or infection with chikungunya virus, a potent IFN inducer. We identified more than 400 zebrafish ISGs, defined as being either directly induced by IFN or induced by the virus in an IFN receptor-dependent manner. Their human orthologues were highly enriched in ISGs, particularly for highly-inducible genes. We identified 72 orthology groups containing ISGs in both zebrafish and human, revealing a core ancestral ISG repertoire, which includes most of the known signaling components of the IFN system. Many downstream effectors were also already present 450 My ago in the common ancestor of tetrapods and bony fish, and diversified as multi-gene families independently in the two lineages. A large proportion of the ISG repertoire is lineage-specific; around 40% of protein-coding zebrafish ISGs had no human orthologue. We identified 14 fish-specific gene families containing multiple ISGs, including finTRIMs. This work illuminates the evolution of the IFN system and provides a rich resource to explore new antiviral mechanisms.Key pointsWe established an exhaustive list of larval zebrafish ISGs.Orthologous ISGs in fish and human identify a large ancestral ISG repertoire.
Hydrothermal vent protistan distribution along the Mariana arc suggests vent endemics may be rare and novel
Authors: Murdock Sheryl A. , Juniper S. Kim 
Published: July 2019

SummaryElucidation of the potential roles of single‐celled eukaryotes (protists) in ecosystem function and trophodynamics in hydrothermal vent ecosystems is reliant on information regarding their abundance, distribution and preference for vent habitats. Using high‐throughput 18S rRNA gene sequencing on a diverse suite of hydrothermally influenced and background water samples, we assess the diversity and distribution of protists and identify potential vent endemics. We found that 95% of the recovered sequences belong to operational taxonomic units (OTUs) with a cosmopolitan distribution across vent and non‐vent habitats. Analysis of ‘vent only’ OTUs found in more than one vent sample and co‐occurrence network analysis comparing protist groups to extremophilic reference organisms suggest that the most likely vent endemics are infrequently encountered, potentially in low abundance, and belong to novel lineages, both at the phylum level and within defined clades of Rhizaria and Stramenopila. Potential endemism is inferred for relatives of known apusomonads, excavates and some clades of Syndiniales. Similarity in community composition among samples was low, indicating a strong stochastic component to protist community assembly and suggesting that rare endemics may serve as a reservoir poised to respond to changing environmental conditions in these dynamic systems.