bluuebunny/crossref_metadata_2025_split huggingface dataset:
Personality profiles differ between patients with epileptic seizures and patients with psychogenic non-epileptic seizures
Authors: Leong Michelle , Wang Albert D , Trainor David , Johnstone Ben , Rayner Genevieve , Kalincik Tomas , Roos Izanne , Kwan Patrick , O’Brien Terence J , Velakoulis Dennis , Malpas Charles B 
Published: July 2019

AbstractAimThe primary aim of the study was to determine whether patients with psychogenic non-epileptic seizures (PNES) have different personality profiles compared to patients with epileptic seizures (ES). The secondary aim was to determine whether any such personality differences could be used to efficiently screen for PNES in clinical settings.BackgroundPNES and ES are often difficult to differentiate, leading to incorrect or delayed diagnosis. While the current gold-standard investigation is video-EEG monitoring (VEM), it is resource intensive and not universally available. Although some research has investigated the differential psychological profiles of PNES and ES patients, most studies have focused on symptoms of psychopathology. The lack of research using modern personality models in PNES and ES presents a gap in knowledge that this study aimed to address.MethodsA retrospective collection of data was conducted on patients who completed the NEO-Five Factor Inventory questionnaire during a VEM admission to the Royal Melbourne Hospital between 2002-2017. Patients were classified as either ES or PNES based on clinical consensus diagnosis. For patients with ES, type of epilepsy and laterality of seizure focus were also recorded. Personality differences were investigated using Bayesian linear mixed effects models. Receiver operating characteristic curve analysis was also performed to generate sensitivities and specificities of individual personality scores.Results305 patients were included in the study. The ‘openness to experience’ domain was the only personality factor demonstrating strong evidence for a group difference (BF10 = 21.55, d = −0.43 [95% CI −0.71, −0.17]), with patients in the PNES group having higher scores compared to the ES group. Within the openness to experience domain, only the ‘aesthetic interest’ facet showed evidence for a group difference (BF10 = 7.98, d = −0.39 [95% CI −0.66, −0.12]). ES patients had lower scores on these measures compared to the normal population, while PNES patients did not. Both openness to experience and aesthetic interest, however, showed poor sensitivities (53%, 46% respectively) and specificities (69%, 46% respectively) for classifying PNES and ES patients. There were no differences between personality profiles in Temporal Lobe Epilepsy (TLE) and non-TLE patients, or in laterality in TLE.ConclusionPatients with ES exhibit lower openness to experience and aesthetic interest compared to patients with PNES and compared to the general population. Despite these differences, the relatively low sensitivity and specificity of these instruments suggests their use is limited in a clinical setting. Nevertheless, these findings open up new avenues of research using modern personality models to further understand patients with epilepsy and related presentations.
The Gut Microbiome of Exudivorous Marmosets in the Wild and Captivity
Authors: Malukiewicz Joanna , Cartwright Reed A. , Dergam Jorge A. , Igayara Claudia S. , Kessler Sharon , Moreira Silvia B. , Nash Leanne T. , Nicola Patricia A. , Pereira Luiz C.M. , Pissinatti Alcides , Ruiz-Miranda Carlos R. , Ozga Andrew T. , Quirino Adriana A. , Roos Christian , Silva Daniel L. , Stone Anne C. , Grativol Adriana D. 
Published: July 2019

ABSTRACTMammalian captive dietary specialists like folivores are prone to gastrointestinal distress and primate dietary specialists suffer the greatest gut microbiome diversity losses in captivity compared to the wild. Marmosets represent another group of dietary specialists, exudivores that eat plant exudates, but whose microbiome remains relatively less studied. The common occurrence of gastrointestinal distress in captive marmosets prompted us to study the Callithrix gut microbiome composition and predictive function through bacterial 16S ribosomal RNA V4 region sequencing. We sampled 59 wild and non-wild Callithrix across four species and their hybrids. Host environment had a stronger effect on the gut microbiome than host taxon. Wild Callithrix gut microbiomes were enriched for Bifidobacterium, which process host-indigestible carbohydrates. Captive marmoset guts were enriched for Enterobacteriaceae, a family containing pathogenic bacteria. While gut microbiome function was similar across marmosets, Enterobacteriaceae seem to carry out most functional activities in captive host guts. More diverse bacterial taxa seem to perform gut functions in wild marmosets, with Bifidobacterium being important for carbohydrate metabolism. Non-wild marmosets showed gut microbiome composition aspects seen in human gastrointestinal diseases. Thus, captivity may perturb the exudivore gut microbiome, which raises implications for captive exudivore welfare and calls for husbandry modifications.
High-resolution view of the type III secretion export apparatusin situreveals membrane remodeling and a secretion pathway
Authors: Butan Carmen , Lara-Tejero Maria , Li Wenwei , Liu Jun , Galán Jorge E. 
Published: July 2019

AbstractType III protein secretion systems are essential virulence factors for many important pathogenic bacteria. The entire protein secretion machine is composed of several substructures that organize into a holostructure or injectisome. The core component of the injectisome is the needle complex, which houses the export apparatus that serves as a gate for the passage of the secreted proteins through the bacterial inner membrane. Here we describe a high-resolution structure of the export apparatus of theSalmonellatype III secretion system in association with the needle complex and the underlying bacterial membrane, both in isolation andin situ. We show the precise location of the core export apparatus components within the injectisome and bacterial envelope and demonstrate that their deployment results in major membrane remodeling and thinning, which may be central for the protein translocation process. We also show that InvA, a critical export apparatus component, forms a multi-ring cytoplasmic conduit that provides a pathway for the type III secretion substrates to reach the entrance of the export gate. Combined with structure-guided mutagenesis, our studies provide major insight into potential mechanisms of protein translocation and injectisome assembly.
Viscoadaptation controls intracellular reaction rates in response to heat and energy availability
Authors: Persson Laura , Ambati Vardhaan S. , Brandman Onn 
Published: July 2019

Summary/AbstractCells must precisely orchestrate thousands of reactions in both time and space. Yet reaction kinetics are highly dependent on uncontrollable environmental conditions such as temperature. Here, we report a novel mechanism by which budding yeast influence reaction rates through adjustment of intracellular viscosity. This “viscoadaptation” is achieved by production of two carbohydrates, trehalose and glycogen, which combine to create a more viscous cellular environment in which biomolecules retain solubility. We demonstrate that viscoadaptation functions as both an acute response to temperature increase as well as a homeostatic mechanism, allowing cells grown at temperatures spanning from 22°C to 40°C to maintain equivalent rates of intracellular diffusion and diffusion-controlled chemical reactions. Multiple conditions that lower ATP trigger viscoadaptation, suggesting that viscoadaptation may be a general cellular response to low energy. Viscoadaptation reveals viscosity to be a tunable property of cells through which they can regulate diffusion-controlled processes dynamically in response to a changing environment.
Energy landscape analysis elucidates the multistability of ecological communities across environmental gradients
Authors: Suzuki Kenta , Nakaoka Shinji , Fukuda Shinji , Masuya Hiroshi 
Published: July 2019

AbstractCompositional multistability is widely observed in multispecies ecological communities. Since differences in community composition often lead to differences in community function, understanding compositional multistability is essential to comprehend the role of biodiversity in maintaining ecosystems. In community assembly studies, it has long been recognized that the order and timing of species migration and extinction influence structure and function of communities. The study of multistability in ecology has focused on the change in dynamical stability across environmental gradients, and was developed mainly for low-dimensional systems. As a result, methodologies for studying the compositional stability of empirical multispecies communities are not well developed. Here, we show that models previously used in ecology can be analyzed from a new perspective - the energy landscape - to unveil compositional stability in observational data. To show that our method can be applicable to real-world ecological communities, we simulated assembly dynamics driven by population level processes, and show that results were mostly robust to different simulation assumptions. Our method reliably captured the change in the overall compositional stability of multispecies communities over environmental change, and indicated a small fraction of community compositions that may be channels for transitions between stable states. When applied to murine gut microbiota, our method showed the presence of two alternative states whose relationship changes with age, and suggested mechanisms by which aging affects the compositional stability of the murine gut microbiota. Our method provides a practical tool to study the compositional stability of communities in a changing world, and will facilitate empirical studies that integrate the concept of multistability from different fields.
Shade-avoidance responses become more aggressive in warm environments
Authors: Romero-Montepaone Sofía , Poodts Sofía , Fischbach Patrick , Sellaro Romina , Zurbriggen Matias D. , Casal Jorge J. 
Published: July 2019

AbstractWhen exposed to neighbour signals, competitive plants increase the growth of the stem to reduce the degree of current or future shade. Plants can experience similar neighbour cues under different weather conditions and the aim of this work is to investigate the impact of daily average temperature and irradiance and thermal amplitude on the magnitude of shade-avoidance responses in Arabidopsis thaliana. For this purpose, we first generated a growth database and elaborated under controlled conditions a model that predicts hypocotyl growth during the photoperiod as a function of the light-modulated activity of the main photo-sensory receptors (phytochromes A and B, cryptochromes 1 and 2), temperature-modulated activity of phytochrome B and an independent temperature input. Thermal amplitude (lower temperatures during the morning and afternoon that at midday) reduced growth of genotypes with normally fast morning growth, and this effect was incorporated to the model. Thermal amplitude also decreased the abundance of the growth-promoting transcription factor PHYTOCHROME-INTERACTING FACTOR 4. The model predicted growth in the field through different seasons with reasonable accuracy. Then, we used the model in combination with a worldwide dataset of current and future whether conditions. The analysis predicted enhanced shade-avoidance responses as a result of higher temperatures due to the geographical location or global warming. Irradiance and thermal amplitude had no effects. These trends were also observed for our local growth measurements. We conclude that, if water and nutrients do not become limiting, warm environments enhance the shade avoidance response.
Regulatory T cells control the dynamic and site-specific polarization of total CD4 T cells followingSalmonellainfection
Authors: Clay Slater L. , Bravo-Blas Alberto , Wall Daniel M. , MacLeod Megan K.L. , Milling Simon W. F. 
Published: July 2019

ABSTRACTFoxP3+regulatory T cells (Tregs) control inflammation and maintain mucosal homeostasis, but their functions during infection are poorly understood. Th1, Th2 and Th17 cells can be identified by master transcription factors (TFs) T-bet, GATA3 and RORγT; Tregs also express these TFs. While T-bet+Tregs can selectively suppress Th1 cells, it is unclear whether distinct Treg populations can alter Th bias. To address this, we usedSalmonella entericaserotype Typhimurium to induce non-lethal colitis. Following infection, we observed an early colonic Th17 response within total CD4 T cells, followed by a Th1 bias. The early Th17 response, which contains both Salmonella-specific and non-Salmonella-specific cells, parallels an increase in T-bet+Tregs. Later, Th1 cells and RORγT+Tregs dominate. This reciprocal dynamic may indicate that Tregs selectively suppress Th cells, shaping the immune response. Treg depletion 1-2 days post-infection shifted the early Th17 response to a Th1 bias; however, depletion 6-7 days post-infection abrogated the Th1 bias. Thus, Tregs are necessary for the early Th17 response, and for a maximal Th1 response later. These data show that Tregs shape the overall tissue CD4 T cell response and highlight the potential for subpopulations of Tregs to be used in targeted therapeutic approaches.
PAREameters: computational inference of plant microRNA-mRNA targeting rules using RNA sequencing data
Authors: Thody Joshua , Moulton Vincent , Mohorianu Irina 
Published: July 2019

ABSTRACTMicroRNAs (miRNAs) are short, non-coding RNAs that influence the translation-rate of mRNAs by directing the RNA-induced silencing complex to sequence-specific targets. In plants, this typically results in cleavage and subsequent degradation of the mRNA. This can be captured on a high-throughput scale using degradome sequencing, which supports miRNA target prediction by aligning degradation fragments to reference mRNAs enabling the identification of causal miRNA(s). The current criteria used for target prediction were inferred on experimentally validated A. thaliana interactions, which were adapted to fit that specific subset of miRNA interactions. In addition, the miRNA pathway in other organisms may have acquired specific changes, e.g. lineage-specific miRNAs or new miRNA-mRNA interactions, thus previous criteria may not be optimal. We present a new tool, PAREameters, for inferring targeting criteria from RNA sequencing datasets; the stability of inferred criteria under subsampling and the effect of input-size are discussed. We first evaluate its performance using experimentally validated miRNA-mRNA interactions in multiple A. thaliana datasets, including conserved and species-specific miRNAs. We then perform comprehensive analyses on the differences in flower miRNA-mRNA interactions in several non-model organisms and quantify the observed variations. PAREameters highlights an increase in sensitivity on most tested datasets when data-inferred criteria are used.
Microevolution in the major outer membrane protein OmpA ofAcinetobacter baumannii
Authors: Viale Alejandro M. , Evans Benjamin A. 
Published: July 2019

AbstractAcinetobacter baumanniiis nowadays a relevant nosocomial pathogen characterized by multidrug resistance (MDR) and concomitant difficulties to treat infections. OmpA is the most abundantA. baumanniiouter membrane (OM) protein, and is involved in virulence, host cell recognition, biofilm formation, regulation of OM stability, permeability, and antibiotic resistance. OmpA members are two-domain proteins with an N-terminal eight-stranded β-barrel domain with four external loops (ELs) interacting with the environment, and a C-terminal periplasmic domain binding non-covalently to the peptidoglycan. Here, we combined data from genome sequencing, phylogenetic, and multilocus sequence analyses from 242 strains of theAcinetobacter calcoaceticus/Acinetobacter baumanniicomplex (ACB), 222 fromA. baumannii, to exploreompAmicroevolutionary divergence. Five majorompAvariant groups were identified (V1 to V5) comprising 50 different alleles coding for 29 different proteins. Polymorphisms were concentrated in 5 regions corresponding to the four ELs and the C-terminal end, and provided evidence for different intra-genic recombination events.ompAvariants were not randomly distributed across theA. baumanniiphylogeny, with the most frequent V1a1 allele almost exclusive to clonal complex 1 (CC1) strains and the second most frequent V2a1 allele found in the majority of CC2 strains. Evidence was found for assortative exchanges ofompAalleles not only between differentA. baumanniiclonal lineages, but also different ACB species. WithinA. baumannii ompAnon-synonymous substitutions were concentrated in the ELs regions, but were more abundant in the transmembrane regions between differentAcinetobacterspecies. The overall results have implications forA. baumanniievolution, epidemiology, virulence, and vaccine design.ImportanceAcinetobacter baumanniiis an increasing MDR threat in nosocomial settings associated with prolonged hospitalization and concomitantly increased healthcare costs. The mainA. baumanniiOM protein, OmpA, is a multifaceted two-domain protein implicated in host cell recognition and adhesion, cytotoxicity, biofilm formation, and as a slow porin for antibiotics and small hydrophilic nutrients.A. baumanniiOmpA has been proposed as a potential target for anti-virulence drugs and as a vaccine candidate. Given the many interactions of this protein with environmental factors including host defenses, it is certainly subjected to many selective pressures. Here, we analyzed the microevolution of this OM protein in theA. baumanniipopulation to obtain clues on the extent to which selection in the clinical setting has shaped this protein. The results provide relevant information on the main causes driving evolution of this protein, with potential implications inA. baumanniiepidemiology, virulence, and vaccine design.
ARL13B regulates Sonic Hedgehog signaling from outside primary cilia
Authors: Gigante Eduardo D. , Taylor Megan R. , Ivanova Anna A. , Kahn Richard A. , Caspary Tamara 
Published: July 2019

AbstractARL13B is a regulatory GTPase highly enriched in cilia. Complete loss ofArl13bdisrupts cilia architecture, protein trafficking and Sonic hedgehog signaling. To determine whether ARL13B is required within cilia, we knocked in a cilia-excluded variant of ARL13B (V358A) and showed it retains all known biochemical function. We found that ARL13BV358Aprotein was expressed but could not be detected in cilia, even when retrograde ciliary transport was blocked. We showedArl13bV358A/V358Amice are viable and fertile with normal Shh signal transduction. However, in contrast to wild type cilia,Arl13bV358A/V358Acells displayed short cilia and lacked ciliary ARL3 and INPP5E. These data indicate that ARL13B’s role within cilia can be uncoupled from its function outside of cilia. Furthermore, these data imply that the cilia defects upon complete absence of ARL13B do not underlie the alterations in Shh transduction, which is unexpected given the requirement of cilia for Shh transduction.
Targeting tRNA-Synthetase Interactions towards Novel Therapeutic Discovery Against Eukaryotic Pathogens
Authors: Kelly Paul , Hadi-Nezhad Fatemeh , Liu Dennis , Lawrence Travis J. , Linington Roger G. , Ibba Michael , Ardell David H. 
Published: July 2019

AbstractThe development of chemotherapies against eukaryotic pathogens is especially challenging because of both the evolutionary conservation of drug targets between host and parasite, and the evolution of strain-dependent drug resistance. There is a strong need for new nontoxic drugs with broad-spectrum activity against trypanosome parasites such as Leishmania and Trypanosoma. A relatively untested approach is to target macromolecular interactions in parasites rather than small molecular interactions, under the hypothesis that the features specifying macromolecular interactions diverge more rapidly through coevolution. We computed tRNA Class-Informative Features in humans and eight clades of trypanosomes, identifying parasite-specific informative features (including base-pairs and base mis-pairs) that are broadly conserved over approximately 250 million years of trypanosome evolution. Validating these observations, we demonstrated biochemically that tRNA:aminoacyl-tRNA synthetase interactions are a promising target for anti-trypanosomal drug discovery. From a marine natural products extract library, we identified several fractions with inhibitory activity toward Leishmania major alanyl-tRNA synthetase (AlaRS) but no activity against the human homolog. These marine natural products extracts showed cross-reactivity towards Trypanosoma cruzi AlaRS indicating the broad-spectrum potential of our network predictions. These findings support a systems biology model in which combination chemotherapies that target multiple tRNA-synthetase interactions should be comparatively less prone to the emergence of resistance than conventional single drug therapies.Author SummaryTrypanosome parasites pose a significant health risk worldwide. Conventional drug development strategies have proven challenging given the high conservation between humans and pathogens, with off-target toxicity being a common problem. Protein synthesis inhibitors have historically been an attractive target for antimicrobial discovery against bacteria, and more recently for eukaryotic pathogens. Here we propose that exploiting pathogen-specific tRNA-synthetase interactions offers the potential for highly targeted drug discovery. To this end, we improved tRNA gene annotations in trypanosome genomes, identified functionally informative trypanosome-specific tRNA features, and showed that these features are highly conserved over approximately 250 million years of trypanosome evolution. Highlighting the species-specific and broad-spectrum potential of our approach, we identified natural product inhibitors against the parasite translational machinery that have no effect on the homologous human enzyme.
Impact of four common hydrogels on amyloid-β (Aβ) aggregation and cytotoxicity: Implications for 3D models of Alzheimer’s disease
Authors: Simpson Laura W. , Szeto Gregory L. , Boukari Hacene , Good Theresa A. , Leach Jennie B. 
Published: July 2019

AbstractThe properties of a hydrogel utilized in 3D culture can influence cell phenotype and morphology, yielding striking similarities to cellular processes that occurin vivo. Indeed, research areas including regenerative medicine, tissue engineering, cancer models, and stem cell cultures have readily utilized 3D biomaterials to investigate cell biological questions. However, cells are only one component of this milieu. Macromolecules play roles as bioactive factors and physical structures. Yet, investigations of macromolecular biophysics largely focus on pure molecules in dilute solution. Biophysical processes such as protein aggregation underlie diseases including Alzheimer’s disease, which is hallmarked by accumulated neurotoxic amyloid-β (Aβ) aggregates. Previously, we demonstrated that Aβ cytotoxicity is attenuated when cells are cultured within type I collagen hydrogels vs. on 2D substrates. Here, we investigated whether this phenomenon is conserved when Aβ is confined within hydrogels of varying physiochemical properties, notably mesh size and bioactivity. We investigated Aβ structure and aggregation kinetics in solution and in hydrogels (collagen, agarose, hyaluronic acid and polyethylene glycol) using fluorescence correlation spectroscopy and thioflavin T assays. Our results reveal that all hydrogels tested were associated with Aβ cytotoxicity attenuation. We suggest that confinement itself imparts a profound effect, possibly by stabilizing Aβ structures and shifting the aggregate equilibrium toward larger species. It is likely that the milieu that exist within cells and tissues also influences protein-protein interactions; thus, we suggest that it is critical to evaluate whether protein structure, function, and stability are altered in 3D systems vs. ideal solutions and 2D culture.