Higher order glass-transition singularities in colloidal systems with attractive interactions

The transition from a liquid to a glass in colloidal suspensions of particles interacting through a hard core plus an attractive square-well potential is studied within the mode-coupling-theory framework. When the width of the attractive potential is much shorter than the hard-core diameter, a reentrant behavior of the liquid-glass line, and a glass-glass-transition line are found in the temperature-density plane of the model. For small well-width values, the glass-glass-transition line terminates in a third order bifurcation point, i.e. in a A_3 (cusp) singularity. On increasing the square-well width, the glass-glass line disappears, giving rise to a fourth order A_4 (swallow-tail) singularity at a critical well width. Close to the A_3 and A_4 singularities the decay of the density correlators shows stretching of huge dynamical windows, in particular logarithmic time dependence.Comment: 19 pages, 12 figures, Phys. Rev. E, in prin

Neural modulation of directed forgetting by valence and arousal: an event-related potential study

Intentional forgetting benefits memory by removing no longer needed information and promoting processing of more relevant materials. This study sought to understand how the behavioural and neurophysiological representation of intentional forgetting would be impacted by emotion. We took a novel approach by examining the unique contribution of both valence and arousal on emotional directed forgetting. Participants completed an item directed forgetting task for positive, negative, and neutral words at high and lower levels of arousal while brain activity was recorded using electroencephalography (EEG). Behaviourally, recognition of to-be-remembered (TBR) and to-be-forgotten (TBF) items varied as a function of valence and arousal with reduced directed forgetting for high arousing negative and neutral words. In the brain, patterns of frontal and posterior activation in response to TBF and TBR cues respectively replicated prior EEG evidence to support involvement of inhibitory and selective rehearsal mechanisms in item directed forgetting. Interestingly, emotion only impacted cue-related posterior activity, which varied depending on specific interactions between valence and arousal. Together, results suggest that the brain handles valence and arousal differently and highlights the importance of considering in a collective manner the multidimensional nature of emotion in experimentation

Conformational states of macromolecular assemblies explored by integrative structure calculation

A detailed description of macromolecular assemblies in multiple conformational states can be very valuable for understanding cellular processes. At present, structural determination of most assemblies in different biologically relevant conformations cannot be achieved by a single technique and thus requires an integrative approach that combines information from multiple sources. Different techniques require different computational methods to allow efficient and accurate data processing and analysis. Here, we summarize the latest advances and future challenges in computational methods that help the interpretation of data from two techniques—mass spectrometry and three-dimensional cryo-electron microscopy (with focus on alignment and classification of heterogeneous subtomograms from cryo-electron tomography). We evaluate how new developments in these two broad fields will lead to further integration with atomic structures to broaden our picture of the dynamic behavior of assemblies in their native environment

Developmental timing of CCM2 loss influences cerebral cavernous malformations in mice

As revealed in a new model of cerebral cavernous malformations (CCM), the timing of ablation of Ccm genes determines whether or not CCM lesions arise in brain and retina venous beds

Improved ability of biological and previous caries multimarkers to predict caries disease as revealed by multivariate PLS modelling

<p>Abstract</p> <p>Background</p> <p>Dental caries is a chronic disease with plaque bacteria, diet and saliva modifying disease activity. Here we have used the PLS method to evaluate a multiplicity of such biological variables (n = 88) for ability to predict caries in a cross-sectional (baseline caries) and prospective (2-year caries development) setting.</p> <p>Methods</p> <p>Multivariate PLS modelling was used to associate the many biological variables with caries recorded in thirty 14-year-old children by measuring the numbers of incipient and manifest caries lesions at all surfaces.</p> <p>Results</p> <p>A wide but shallow gliding scale of one fifth caries promoting or protecting, and four fifths non-influential, variables occurred. The influential markers behaved in the order of plaque bacteria > diet > saliva, with previously known plaque bacteria/diet markers and a set of new protective diet markers. A differential variable patterning appeared for new versus progressing lesions. The influential biological multimarkers (n = 18) predicted baseline caries better (ROC area 0.96) than five markers (0.92) and a single lactobacilli marker (0.7) with sensitivity/specificity of 1.87, 1.78 and 1.13 at 1/3 of the subjects diagnosed sick, respectively. Moreover, biological multimarkers (n = 18) explained 2-year caries increment slightly better than reported before but predicted it poorly (ROC area 0.76). By contrast, multimarkers based on previous caries predicted alone (ROC area 0.88), or together with biological multimarkers (0.94), increment well with a sensitivity/specificity of 1.74 at 1/3 of the subjects diagnosed sick.</p> <p>Conclusion</p> <p>Multimarkers behave better than single-to-five markers but future multimarker strategies will require systematic searches for improved saliva and plaque bacteria markers.</p

Respiratory disease and the role of oral bacteria

The relationship between oral health and systemic conditions, including the association between poor oral hygiene, periodontal disease, and respiratory disease, has been increasingly debated over recent decades. A considerable number of hypotheses have sought to explain the possible role of oral bacteria in the pathogenesis of respiratory diseases, and some clinical and epidemiological studies have found results favoring such an association. This review discusses the effect of oral bacteria on respiratory disease, briefly introduces the putative biological mechanisms involved, and the main factors that could contribute to this relationship. It also describes the role of oral care for individuals who are vulnerable to respiratory infections

Characterization of an Nmr Homolog That Modulates GATA Factor-Mediated Nitrogen Metabolite Repression in Cryptococcus neoformans

Nitrogen source utilization plays a critical role in fungal development, secondary metabolite production and pathogenesis. In both the Ascomycota and Basidiomycota, GATA transcription factors globally activate the expression of catabolic enzyme-encoding genes required to degrade complex nitrogenous compounds. However, in the presence of preferred nitrogen sources such as ammonium, GATA factor activity is inhibited in some species through interaction with co-repressor Nmr proteins. This regulatory phenomenon, nitrogen metabolite repression, enables preferential utilization of readily assimilated nitrogen sources. In the basidiomycete pathogen Cryptococcus neoformans, the GATA factor Gat1/Are1 has been co-opted into regulating multiple key virulence traits in addition to nitrogen catabolism. Here, we further characterize Gat1/Are1 function and investigate the regulatory role of the predicted Nmr homolog Tar1. While GAT1/ARE1 expression is induced during nitrogen limitation, TAR1 transcription is unaffected by nitrogen availability. Deletion of TAR1 leads to inappropriate derepression of non-preferred nitrogen catabolic pathways in the simultaneous presence of favoured sources. In addition to exhibiting its evolutionary conserved role of inhibiting GATA factor activity under repressing conditions, Tar1 also positively regulates GAT1/ARE1 transcription under non-repressing conditions. The molecular mechanism by which Tar1 modulates nitrogen metabolite repression, however, remains open to speculation. Interaction between Tar1 and Gat1/Are1 was undetectable in a yeast two-hybrid assay, consistent with Tar1 and Gat1/Are1 each lacking the conserved C-terminus regions present in ascomycete Nmr proteins and GATA factors that are known to interact with each other. Importantly, both Tar1 and Gat1/Are1 are suppressors of C. neoformans virulence, reiterating and highlighting the paradigm of nitrogen regulation of pathogenesis

The Australasian Resuscitation In Sepsis Evaluation : fluids or vasopressors in emergency department sepsis (ARISE FLUIDS), a multi-centre observational study describing current practice in Australia and New Zealand

Objectives: To describe haemodynamic resuscitation practices in ED patients with suspected sepsis and hypotension. Methods: This was a prospective, multicentre, observational study conducted in 70 hospitals in Australia and New Zealand between September 2018 and January 2019. Consecutive adults presenting to the ED during a 30-day period at each site, with suspected sepsis and hypotension (systolic blood pressure <100 mmHg) despite at least 1000 mL fluid resuscitation, were eligible. Data included baseline demographics, clinical and laboratory variables and intravenous fluid volume administered, vasopressor administration at baseline and 6- and 24-h post-enrolment, time to antimicrobial administration, intensive care admission, organ support and in-hospital mortality. Results: A total of 4477 patients were screened and 591 were included with a mean (standard deviation) age of 62 (19) years, Acute Physiology and Chronic Health Evaluation II score 15.2 (6.6) and a median (interquartile range) systolic blood pressure of 94 mmHg (87–100). Median time to first intravenous antimicrobials was 77 min (42–148). A vasopressor infusion was commenced within 24 h in 177 (30.2%) patients, with noradrenaline the most frequently used (n = 138, 78%). A median of 2000 mL (1500–3000) of intravenous fluids was administered prior to commencing vasopressors. The total volume of fluid administered from pre-enrolment to 24 h was 4200 mL (3000–5661), with a range from 1000 to 12 200 mL. Two hundred and eighteen patients (37.1%) were admitted to an intensive care unit. Overall in-hospital mortality was 6.2% (95% confidence interval 4.4–8.5%). Conclusion: Current resuscitation practice in patients with sepsis and hypotension varies widely and occupies the spectrum between a restricted volume/earlier vasopressor and liberal fluid/later vasopressor strategy

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe