Astrobiological Complexity with Probabilistic Cellular Automata

Search for extraterrestrial life and intelligence constitutes one of the major endeavors in science, but has yet been quantitatively modeled only rarely and in a cursory and superficial fashion. We argue that probabilistic cellular automata (PCA) represent the best quantitative framework for modeling astrobiological history of the Milky Way and its Galactic Habitable Zone. The relevant astrobiological parameters are to be modeled as the elements of the input probability matrix for the PCA kernel. With the underlying simplicity of the cellular automata constructs, this approach enables a quick analysis of large and ambiguous input parameters' space. We perform a simple clustering analysis of typical astrobiological histories and discuss the relevant boundary conditions of practical importance for planning and guiding actual empirical astrobiological and SETI projects. In addition to showing how the present framework is adaptable to more complex situations and updated observational databases from current and near-future space missions, we demonstrate how numerical results could offer a cautious rationale for continuation of practical SETI searches.Comment: 37 pages, 11 figures, 2 tables; added journal reference belo

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Encephalomyocarditis virus may use different pathways to initiateinfection of primary human cardiomyocytes

Encephalomyocarditis virus (EMCV) caninfect a wide range of vertebrate species including swineand non-human primates, but few data are available forhumans. We therefore wanted to gain further insight intothe mechanisms involved in EMCV infection of humancells. For this purpose, we analyzed the permissiveness ofprimary human cardiomyocytes towards two strains ofEMCV; a pig myocardial strain (B279/95) and a rat strain(1086C). In this study, we show that both strains productivelyinfect primary human cardiomyocytes and inducecomplete cytolysis. Binding and infection inhibitionexperiments indicated that attachment and infection areindependent of sialic acid and heparan sulfate for B279/95and dependent for 1086C. Sequence comparison betweenthe two strains and three-dimensional analysis of the capsidrevealed that six of the seven variable residues are surfaceexposed,suggesting a role for these amino acids in binding.Moreover, analysis of variants isolated from the 1086Cstrain revealed the importance of lysine 231 of VP1 in theattachment of EMCV to cell-surface sialic acid residues.Together, these results show a potential for EMCV strainsto use at least two different binding possibilities to initiateinfection and provide new insights into the mechanismsinvolved in primary human cell recognition by EMCV

The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Four priority areas to advance invasion science in the face of rapid environmental change

Unprecedented rates of introduction and spread of non-native species pose burgeoning challenges to biodiversity, natural resource management, regional economies, and human health. Current biosecurity efforts are failing to keep pace with globalization, revealing critical gaps in our understanding and response to invasions. Here, we identify four priority areas to advance invasion science in the face of rapid global environmental change. First, invasion science should strive to develop a more comprehensive framework for predicting how the behavior, abundance, and interspecific interactions of non-native species vary in relation to conditions in receiving environments and how these factors govern the ecological impacts of invasion. A second priority is to understand the potential synergistic effects of multiple co-occurring stressors— particularly involving climate change—on the establishment and impact of non-native species. Climate adaptation and mitigation strategies will need to consider the possible consequences of promoting non-native species, and appropriate management responses to non-native species will need to be developed. The third priority is to address the taxonomic impediment. The ability to detect and evaluate invasion risks is compromised by a growing deficit in taxonomic expertise, which cannot be adequately compensated by new molecular technologies alone. Management of biosecurity risks will become increasingly challenging unless academia, industry, and governments train and employ new personnel in taxonomy and systematics. Fourth, we recommend that internationally cooperative biosecurity strategies consider the bridgehead effects of global dispersal networks, in which organisms tend to invade new regions from locations where they have already established. Cooperation among countries to eradicate or control species established in bridgehead regions should yield greater benefit than independent attempts by individual countries to exclude these species from arriving and establishing

Bridging the Gulf: Phytophthora and Downy Mildews Are Connected by Rare Grass Parasites

Downy mildews and root and foliar rots caused by Phytophthora are among the most destructive plant pathogens and therefore have attracted considerable attention during the past two decades. Although it has been realized that a close phylogenetic relationship exists, so far sharp distinction has been made between the obligate biotrophic downy mildews and the hemibiotrophic Phytophthora. In the study presented here, it is shown that a continuum of character states from hemibiotrophic Phytophthora species to obligate biotrophic downy mildews is present. Intermediate character states between downy mildews and Phytophthora species exist in several rare parasites of grasses, which are not embedded within the major clades of the downy mildews but are placed sister to these, with unresolved affinities to both these clades and to Phytophthora. They still have retained traits hitherto thought to be exclusive for Phytophthora. A careful review of previous research is presented and it is highlighted that uniquely for downy mildews, Poakatesthia may form an intracellular mycelium, growing through several host cells. In addition, scanning electron microscopy reveals that sporangiophore growth is not determinate in Viennotia and that outgrowth from sporangiophores is very similar to Phytophthora infestans. It is concluded that the sharp morphological distinction between downy mildews and Phytophthora species (that are often placed in separate families and even different orders), is rather artificial, since all features thought to be exclusive to Phytophthora or the downy mildews are united in the rare grass-parasitizing down mildew genera Viennotia and Poakatesthia and the enigmatic genus Sclerophthora. Therefore, several paradigms regarding the distinction between Phytophthora and the downy mildews need to be reconsidered

Externalizing behaviors in preadolescents: familial risk to externalizing behaviors and perceived parenting styles

The aim was to investigate the contribution of familial risk to externalizing behaviors (FR-EXT), perceived parenting styles, and their interactions to the prediction of externalizing behaviors in preadolescents. Participants were preadolescents aged 10–12 years who participated in TRAILS, a large prospective population-based cohort study in the Netherlands (N = 2,230). Regression analyses were used to determine the relative contribution of FR-EXT and perceived parenting styles to parent and teacher ratings of externalizing behaviors. FR-EXT was based on lifetime parental externalizing psychopathology and the different parenting styles (emotional warmth, rejection, and overprotection) were based on the child’s perspective. We also investigated whether different dimensions of perceived parenting styles had different effects on subdomains of externalizing behavior. We found main effects for FR-EXT (vs. no FR-EXT), emotional warmth, rejection, and overprotection that were fairly consistent across rater and outcome measures. More specific, emotional warmth was the most consistent predictor of all outcome measures, and rejection was a stronger predictor of aggression and delinquency than of inattention. Interaction effects were found for FR-EXT and perceived parental rejection and overprotection; other interactions between FR-EXT and parenting styles were not significant. Correlations between FR-EXT and perceived parenting styles were absent or very low and were without clinical significance. Predominantly main effects of FR-EXT and perceived parenting styles independently contribute to externalizing behaviors in preadolescents, suggesting FR-EXT and parenting styles to be two separate areas of causality. The relative lack of gene–environment interactions may be due to the epidemiological nature of the study, the preadolescent age of the subjects, the measurement level of parenting and the measurement level of FR-EXT, which might be a consequence of both genetic and environmental factors

Associations with photoreceptor thickness measures in the UK Biobank

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40–69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness