Differential adherence and expression of virulence traits by Candida albicans and Candida parapsilosis in mono- and dual-species cultures in artificial saliva

AIMS: To evaluate specific virulence factors of Candida albicans and Candida parapsilosis clinical oral isolates in mono- and dual-species culture in the presence of artificial saliva. METHODS AND RESULTS: Two of the strains used in this study were isolated from co-infection (C. albicans AM and C. parapsilosis AM2), and the other two were isolated from single infection (C. albicans AC and C. parapsilosis AD). The number of adhered yeast cells was measured and their enzymatic activity was determined simultaneously. In mono-species culture, C. parapsilosis strains adhered to a higher extent to the surface in comparison with the C. albicans strains. In dual-species culture, the C. parapsilosis strains adhered more in the presence of C. albicans AM. Interestingly, C. albicans AM and C. parapsilosis AD adhered to a higher extent when compared with all other co-cultures. In dual-species culture, the enzymatic activity of C. parapsilosis strains in the presence of C. albicans AC was higher than in the presence of C. albicans AM. CONCLUSIONS: The virulence factors of C. albicans and C. parapsilosis differ from strain to strain and are influenced by the presence of other species in culture. SIGNIFICANCE AND IMPACT OF THE STUDY: To understand the expression of virulence factors in Candida dual-species systems.This work was supported by Portuguese Foundation for Science and Technology (FCT) through the grant SFRH/BPD/20987/2004 attributed to Claudia Botelho

A tectonic-rules-based mantle reference frame since 1 billion years ago – implications for supercontinent cycles and plate–mantle system evolution

Understanding the long-term evolution of Earth's plate–mantle system is reliant on absolute plate motion models in a mantle reference frame, but such models are both difficult to construct and controversial. We present a tectonic-rules-based optimization approach to construct a plate motion model in a mantle reference frame covering the last billion years and use it as a constraint for mantle flow models. Our plate motion model results in net lithospheric rotation consistently below 0.25∘ Myr−1, in agreement with mantle flow models, while trench motions are confined to a relatively narrow range of −2 to +2 cm yr−1 since 320 Ma, during Pangea stability and dispersal. In contrast, the period from 600 to 320 Ma, nicknamed the “zippy tricentenary” here, displays twice the trench motion scatter compared to more recent times, reflecting a predominance of short and highly mobile subduction zones. Our model supports an orthoversion evolution from Rodinia to Pangea with Pangea offset approximately 90∘ eastwards relative to Rodinia – this is the opposite sense of motion compared to a previous orthoversion hypothesis based on paleomagnetic data. In our coupled plate–mantle model a broad network of basal mantle ridges forms between 1000 and 600 Ma, reflecting widely distributed subduction zones. Between 600 and 500 Ma a short-lived degree-2 basal mantle structure forms in response to a band of subduction zones confined to low latitudes, generating extensive antipodal lower mantle upwellings centred at the poles. Subsequently, the northern basal structure migrates southward and evolves into a Pacific-centred upwelling, while the southern structure is dissected by subducting slabs, disintegrating into a network of ridges between 500 and 400 Ma. From 400 to 200 Ma, a stable Pacific-centred degree-1 convective planform emerges. It lacks an antipodal counterpart due to the closure of the Iapetus and Rheic oceans between Laurussia and Gondwana as well as due to coeval subduction between Baltica and Laurentia and around Siberia, populating the mantle with slabs until 320 Ma when Pangea is assembled. A basal degree-2 structure forms subsequent to Pangea breakup, after the influence of previously subducted slabs in the African hemisphere on the lowermost mantle structure has faded away. This succession of mantle states is distinct from previously proposed mantle convection models. We show that the history of plume-related volcanism is consistent with deep plumes associated with evolving basal mantle structures. This Solid Earth Evolution Model for the last 1000 million years (SEEM1000) forms the foundation for a multitude of spatio-temporal data analysis approaches

Detection of atherosclerotic cardiovascular disease influences the perceived need for aggressive lipid management

Background and aims Overt atherosclerotic cardiovascular disease (ASCVD) warrants aggressive lipid lowering. Imaging for ambiguous symptoms suggesting ischemia or for clarification of CV risk in asymptomatic individuals often uncovers previously unknown ASCVD. Guidelines do not provide clear recommendations for aggressive lipid lowering in such cases. We explored physicians' perception, as influenced by tests that detect ASCVD, regarding appropriateness of getting to lipid goals and for theoretically accessing proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i). Methods A questionnaire was developed including cases of low to high CV risk, chronic kidney disease (CKD) or type 2 diabetes mellitus (T2DM). Each case was considered with or without angina symptoms and, in turn, whether testing identified previously unknown advanced, early/subclinical or no ASCVD. Synthesis of responses was facilitated by using a scale for perceived appropriateness from 1 (lowest) to 9 (highest). Results Getting to goal and, if not achieved by statins and/or ezetimibe, accessing PCSK9i was considered appropriate in patients with T2DM with preclinical or advanced ASCVD, patients with moderate or high CV risk and advanced ASCVD, patients with CKD or low CV risk with angina symptoms and advanced ASCVD. For most of the remaining cases adding PCSK9i was considered only possibly appropriate. Conclusions Physicians' perception of appropriateness for achieving lipid goals, including access to PCSK9i, is markedly influenced by detection of previously unknown ASCVD. Since these commonly encountered scenarios do not clearly meet current indications for PCSK9i, our data identify pressing areas requiring further research

Left sided inferior vena cava duplication and venous thromboembolism: case report and review of literature

The etiology of venous thromboembolism in young patients is frequently associated with hereditary coagulation abnormalities, immunologic diseases, and neoplasia. The advent of radiological advances, namely Computed Tomography (CT) scans and venography has identified vena cava malformations as a new etiologic factor worthy of consideration. In this case report, we describe the unusual occurrence of venous thromboembolism in association with a duplicated inferior vena cava. Duplications of the inferior vena cava (IVC) are seen with an incidence of 0.2% to 3.0% in the general population. Embryogenesis of the IVC is a complex process involving the intricate formation and regression of numerous anastomoses, potentially leading to various anomalies. We present a 23-year-old Caucasian woman with IVC duplication who developed a deep venous thrombosis and multiple pulmonary emboli. Anomaly of the IVC is a rare example of a congenital condition that predisposes to thromboembolism, presumably by favoring venous stasis. This diagnosis should be considered in patients under the age of 30 with spontaneous occurrence of blood clots

Negative Effects of Paternal Age on Children's Neurocognitive Outcomes Can Be Explained by Maternal Education and Number of Siblings

Background: Recent findings suggest advanced paternal age may be associated with impaired child outcomes, in particular, neurocognitive skills. Such patterns are worrisome given relatively universal trends in advanced countries toward delayed nuptiality and fertility. But nature and nurture are both important for child outcomes, and it is important to control for both when drawing inferences about either pathway. Methods and Findings: We examined cross-sectional patterns in six developmental outcome measures among children in the U.S. Collaborative Perinatal Project (n = 31,346). Many of these outcomes at 8 mo, 4 y, and 7 y of age (Bayley scales, Stanford Binet Intelligence Scale, Graham-Ernhart Block Sort Test, Wechsler Intelligence Scale for Children, Wide Range Achievement Test) are negatively correlated with paternal age when important family characteristics such as maternal education and number of siblings are not included as covariates. But controlling for family characteristics in general and mother’s education in particular renders the effect of paternal age statistically insignificant for most developmental measures. Conclusions: Assortative mating produces interesting relationships between maternal and paternal characteristics that can inject spurious correlation into observational studies via omitted variable bias. Controlling for both nature and nurture reveals little residual evidence of a link between child neurocognitive outcomes and paternal age in these data. Result

Revisiting the association between candidal infection and carcinoma, particularly oral squamous cell carcinoma

Background: Tobacco and alcohol are risk factors associated with cancer of the upper aerodigestive tract, but increasingly the role of infection and chronic inflammation is recognized as being significant in cancer development. Bacteria, particularly Helicobacter pylori, and viruses such as members of the human papilloma virus family and hepatitis B and C are strongly implicated as etiological factors in certain cancers. There is less evidence for an association between fungi and cancer, although it has been recognized for many years that white patches on the oral mucosa, which are infected with Candida, have a greater likelihood of undergoing malignant transformation than those that are not infected. Objective: This article reviews the association between the development of oral squamous cell carcinoma in potentially malignant oral lesions with chronic candidal infection and describes mechanisms that may be involved in Candida-associated malignant transformation

Effective-Range Expansion of the Neutron-Deuteron Scattering Studied by a Quark-Model Nonlocal Gaussian Potential

The S-wave effective range parameters of the neutron-deuteron (nd) scattering are derived in the Faddeev formalism, using a nonlocal Gaussian potential based on the quark-model baryon-baryon interaction fss2. The spin-doublet low-energy eigenphase shift is sufficiently attractive to reproduce predictions by the AV18 plus Urbana three-nucleon force, yielding the observed value of the doublet scattering length and the correct differential cross sections below the deuteron breakup threshold. This conclusion is consistent with the previous result for the triton binding energy, which is nearly reproduced by fss2 without reinforcing it with the three-nucleon force.Comment: 21 pages, 6 figures and 6 tables, submitted to Prog. Theor. Phy

Current Estimates for HIV-1 Production Imply Rapid Viral Clearance in Lymphoid Tissues

It has recently been estimated that a single HIV-1 infected cell produces between and more than viral particles over its life span. Since body-wide estimates of the ratio of free virus to productively infected cells are smaller than and much smaller than , individual virions must be cleared rapidly. This seems difficult to reconcile with the fact that most of the total body virus is trapped on follicular dendritic cells where it can survive for many months. It has also been difficult to reconcile the vast difference in the rates at which the virus is cleared from the blood in rhesus macaques and in chronically infected patients. Here we attempt to reconcile these seemingly contradictory observations by considering the virion clearance rate in various organs and the virion exchange rates between them. The main results are that the per capita clearance rate of free virus in lymphoid tissue should be fast, the virion exchange rate between lymphoid tissue and the blood should be slow, and the comparatively slow previous estimates for the virion clearance rate from the blood correspond to the rate of virion efflux from the blood to other organs where the virus is ultimately cleared

Lack of Trehalose Accelerates H2O2-Induced Candida albicans Apoptosis through Regulating Ca2+ Signaling Pathway and Caspase Activity

Trehalose is a non-reducing disaccharide and can be accumulated in response to heat or oxidative stresses in Candida albicans. Here we showed that a C. albicans tps1Δ mutant, which is deficient in trehalose synthesis, exhibited increased apoptosis rate upon H2O2 treatment together with an increase of intracellular Ca2+ level and caspase activity. When the intracellular Ca2+ level was stimulated by adding CaCl2 or A23187, both the apoptosis rate and caspase activity were increased. In contrast, the presence of two calcium chelators, EGTA and BAPTA, could attenuate these effects. Moreover, we investigated the role of Ca2+ pathway in C. albicans apoptosis and found that both calcineurin and the calcineurin-dependent transcription factor, Crz1p, mutants showed decreased apoptosis and caspase activity upon H2O2 treatment compared to the wild-type cells. Expression of CaMCA1, the only gene found encoding a C. albicans metacaspase, in calcineurin-deleted or Crz1p-deleted cells restored the cell sensitivity to H2O2. Our results suggest that Ca2+ and its downstream calcineurin/Crz1p/CaMCA1 pathway are involved in H2O2 -induced C. albicans apoptosis. Inhibition of this pathway might be the mechanism for the protective role of trehalose in C. albicans