Role of lysozyme inhibitors in the virulence of avian pathogenic Escherichia coli

Lysozymes are key effectors of the animal innate immunity system that kill bacteria by hydrolyzing peptidoglycan, their major cell wall constituent. Recently, specific inhibitors of the three major lysozyme families occuring in the animal kingdom (c-, g- and i-type) have been discovered in Gram-negative bacteria, and it has been proposed that these may help bacteria to evade lysozyme mediated lysis during interaction with an animal host. Escherichia coli produces two inhibitors that are specific for c-type lysozyme (Ivy, Inhibitor of vertebrate lysozyme; MliC, membrane bound lysozyme inhibitor of c-type lysozyme), and one specific for g-type lysozyme (PliG, periplasmic lysozyme inhibitor of g-type lysozyme). Here, we investigated the role of these lysozyme inhibitors in virulence of Avian Pathogenic E. coli (APEC) using a serum resistance test and a subcutaneous chicken infection model. Knock-out of mliC caused a strong reduction in serum resistance and in in vivo virulence that could be fully restored by genetic complementation, whereas ivy and pliG could be knocked out without effect on serum resistance and virulence. This is the first in vivo evidence for the involvement of lysozyme inhibitors in bacterial virulence. Remarkably, the virulence of a ivy mliC double knock-out strain was restored to almost wild-type level, and this strain also had a substantial residual periplasmic lysozyme inhibitory activity that was higher than that of the single knock-out strains. This suggests the existence of an additional periplasmic lysozyme inhibitor in this strain, and indicates a regulatory interaction in the expression of the different inhibitors

Ready for university? A cross national study on students' perceived preparedness for university

Students' preparedness for higher education is seen as one of the main factors affecting first-year attrition or study success. In this paper we report on a cross-national study in which students' preparedness for university was measured before students commenced their study at a university in New Zealand or in the Netherlands. This cross-national project provided a unique opportunity to compare students' perceptions of readiness for university where students are prepared for higher education in quite different secondary school systems. Departing from a transition framework, and comparing the results in both countries using logistic regression techniques to investigate which aspects of readiness could predict perceived preparedness, we discovered similarities in as well as differences between students' perceived readiness for university study. It could be argued that differences are caused by the different educational systems at secondary level. However, overall we can conclude that, in spite of differences between the educational systems in the two countries, many differences were not remarkable or very significant. This has clear implications for how we view the relative importance of secondary school preparation and tertiary induction. We can expect greater benefit from implementing first-year pedagogical practices in universities that would assist students to develop their academic skills, than from demanding that high schools prepare students better

The global expansion of a single ant supercolony

Ants are among the most damaging invasive species, and their success frequently arises from the widespread cooperation displayed by introduced populations, often across hundreds of kilometers. Previous studies of the invasive Argentine ant (Linepithema humile) have shown that introduced populations on different continents each contain a single, vast supercolony and, occasionally, smaller secondary colonies. Here, we perform inter-continental behavioral analyses among supercolonies in North America, Europe, Asia, Hawaii, New Zealand and Australia and show that these far-flung supercolonies also recognize and accept each other as if members of a single, globally distributed supercolony. Furthermore, populations also possess similar genetic and chemical profiles. However, these ants do show aggression toward ants from South Africa and the smaller secondary colonies that occur in Hawaii and California. Thus, the largest and most dominant introduced populations are likely descended from the same ancestral colony and, despite having been established more than 100 years ago, have diverged very little. This apparent evolutionary stasis is surprising because, in other species, some of the most rapid rates of evolutionary change have occurred in introduced populations. Given the spatial extent of the Argentine ant society we report here, there can be little doubt that this intercontinental supercolony represents the most populous known animal society

Artificial intelligence approaches to predicting and detecting cognitive decline in older adults: A conceptual review.

Preserving cognition and mental capacity is critical to aging with autonomy. Early detection of pathological cognitive decline facilitates the greatest impact of restorative or preventative treatments. Artificial Intelligence (AI) in healthcare is the use of computational algorithms that mimic human cognitive functions to analyze complex medical data. AI technologies like machine learning (ML) support the integration of biological, psychological, and social factors when approaching diagnosis, prognosis, and treatment of disease. This paper serves to acquaint clinicians and other stakeholders with the use, benefits, and limitations of AI for predicting, diagnosing, and classifying mild and major neurocognitive impairments, by providing a conceptual overview of this topic with emphasis on the features explored and AI techniques employed. We present studies that fell into six categories of features used for these purposes: (1) sociodemographics; (2) clinical and psychometric assessments; (3) neuroimaging and neurophysiology; (4) electronic health records and claims; (5) novel assessments (e.g., sensors for digital data); and (6) genomics/other omics. For each category we provide examples of AI approaches, including supervised and unsupervised ML, deep learning, and natural language processing. AI technology, still nascent in healthcare, has great potential to transform the way we diagnose and treat patients with neurocognitive disorders

Bacterial infections in cirrhosis: Role of proton pump inhibitors and intestinal permeability

Background Cirrhotic patients are at considerable risk for bacterial infections, possibly through increased intestinal permeability and bacterial overgrowth. Proton pump inhibitors (PPIs) may increase infection risk. We aimed to explore the potential association between PPI use and bacterial infection risk in cirrhotic patients and potential underlying mechanisms in complementary patient and animal models. Materials and methods Bacterial overgrowth was determined in jejunum of 30 rats randomly allocated to 6-week PPI treatment, gastrectomy or no treatment. In 84 consecutive cirrhotic patients, bacterial infection risk was prospectively assessed and related to PPI use. Intestinal permeability was determined by polyethylene glycol (PEG) test in nine healthy individuals and 12 cirrhotic patients. Results Bacterial overgrowth was much more common in jejunum of rats treated with PPI or gastrectomy compared with nontreated rats. Twenty-four patients (29%) developed a bacterial infection during a median follow-up of 28months. Although PPI users tended to experience infection more often than patients without PPI therapy, PPI use was not an independent predictor of bacterial infection (HR 1·2, 95% CI 0·5-3·0, P=0·72), after correction for Child-Pugh class (HR 3·6, 95% CI 1·5-8·7, P=0·004) and age (HR 1·05, 95%CI 1·01-1·09, P=0·02). In cirrhotic patients, 24-h urinary recovery of PEGs 1500 and 3350 was significantly higher compared with healthy controls. Conclusions Although in our animal model PPIs induced intestinal overgrowth, stage of liver disease rather than PPI use was the predominant factor determining infection risk in cirrhotic patients. Increased intestinal permeability may be a factor contributing to infection risk

Trajectories of Self-Efficacy, Depressed Mood, and Anxiety From Admission to Spinal Cord Injury Rehabilitation to 1 Year After Discharge

OBJECTIVE: Self-efficacy (SE) is an important determinant for the psychological adjustment of people with spinal cord injury (SCI). However, little is known about the course of SE during inpatient rehabilitation up to 1 year after discharge. The aim of this study was to determine latent trajectory classes of SE, depressive mood, and anxiety in people with SCI, as well as the interrelationships between these trajectories. DESIGN: Longitudinal inception cohort study. SETTING: Eight specialized SCI rehabilitation centers. PARTICIPANTS: The participants (N=268) were mainly men 183 of 268 (68.3%) with a mean age of 55.6 years. Almost half had a traumatic SCI 135 of 268 (50.4%) and tetraplegia (53.7%), and the minority had a motor complete SCI (32.2%). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SE was measured using the University of Washington Self-Efficacy Scale. In addition, the Hospital Anxiety and Depression Scale was used to asses distress and perform dual trajectory modeling analyses. RESULTS: Three trajectories of SE, indicating low, middle, and high SE, could be distinguished. Furthermore, a 2-class trajectory solution for depressive mood and a 4-class solution for anxiety were found to be most suitable. All trajectories were stable over time. Developmental connections between SE and depressive mood and between SE and anxiety were revealed. In particular, participants who adjusted well, reporting low scores on depressive mood and anxiety, could be identified by their high SE scores. However, the group of participants with high depressive mood scores and anxiety scores could not always be identified based on their SE trajectory. CONCLUSIONS: In accordance with our hypotheses, distinct trajectories of SE, depressive mood, and anxiety were identified and high probabilities that SE trajectories were interrelated to the trajectories from depressive mood and anxiety were confirmed. Concurrent screening for SE and distress might best detect people at risk for adjustment problems

Regulation and Essentiality of the StAR-related Lipid Transfer (START) Domain-containing Phospholipid Transfer Protein PFA0210c in Malaria Parasites.

StAR-related lipid transfer (START) domains are phospholipid- or sterol-binding modules that are present in many proteins. START domain-containing proteins (START proteins) play important functions in eukaryotic cells, including the redistribution of phospholipids to subcellular compartments and delivering sterols to the mitochondrion for steroid synthesis. How the activity of the START domain is regulated remains unknown for most of these proteins. The Plasmodium falciparum START protein PFA0210c (PF3D7_0104200) is a broad-spectrum phospholipid transfer protein that is conserved in all sequenced Plasmodium species and is most closely related to the mammalian START proteins STARD2 and STARD7. PFA0210c is unusual in that it contains a signal sequence and a PEXEL export motif that together mediate transfer of the protein from the parasite to the host erythrocyte. The protein also contains a C-terminal extension, which is very uncommon among mammalian START proteins. Whereas the biochemical properties of PFA0210c have been characterized, the function of the protein remains unknown. Here, we provide evidence that the unusual C-terminal extension negatively regulates phospholipid transfer activity. Furthermore, we use the genetically tractable Plasmodium knowlesi model and recently developed genetic technology in P. falciparum to show that the protein is essential for growth of the parasite during the clinically relevant asexual blood stage life cycle. Finally, we show that the regulation of phospholipid transfer by PFA0210c is required in vivo, and we identify a potential second regulatory domain. These findings provide insight into a novel mechanism of regulation of phospholipid transfer in vivo and may have important implications for the interaction of the malaria parasite with its host cell