Evolution of asexual and sexual reproduction in the aspergilli

Aspergillus nidulans has long-been used as a model organism to gain insights into the genetic basis of asexual and sexual developmental processes both in other members of the genus Aspergillus, and filamentous fungi in general. Paradigms have been established concerning the regulatory mechanisms of conidial development. However, recent studies have shown considerable genome divergence in the fungal kingdom, questioning the general applicability of findings from Aspergillus, and certain longstanding evolutionary theories have been questioned. The phylogenetic distribution of key regulatory elements of asexual reproduction in A. nidulans was investigated in a broad taxonomic range of fungi. This revealed that some proteins were well conserved in the Pezizomycotina (e.g. AbaA, FlbA, FluG, NsdD, MedA, and some velvet proteins), suggesting similar developmental roles. However, other elements (e.g. BrlA) had a more restricted distribution solely in the Eurotiomycetes, and it appears that the genetic control of sporulation seems to be more complex in the aspergilli than in some other taxonomic groups of the Pezizomycotina. The evolution of the velvet protein family is discussed based on the history of expansion and contraction events in the early divergent fungi. Heterologous expression of the A. nidulans abaA gene in Monascus ruber failed to induce development of complete conidiophores as seen in the aspergilli, but did result in increased conidial production. The absence of many components of the asexual developmental pathway from members of the Saccharomycotina supports the hypothesis that differences in the complexity of their spore formation is due in part to the increased diversity of the sporulation machinery evident in the Pezizomycotina. Investigations were also made into the evolution of sex and sexuality in the aspergilli. MAT loci were identified from the heterothallic Aspergillus (Emericella) heterothallicus and Aspergillus (Neosartorya) fennelliae and the homothallic Aspergillus pseudoglaucus (=Eurotium repens). A consistent architecture of the MAT locus was seen in these and other heterothallic aspergilli whereas much variation was seen in the arrangement of MAT loci in homothallic aspergilli. This suggested that it is most likely that the common ancestor of the aspergilli exhibited a heterothallic breeding system. Finally, the supposed prevalence of asexuality in the aspergilli was examined. Investigations were made using A. clavatus as a representative ‘asexual’ species. It was possible to induce a sexual cycle in A. clavatus given the correct MAT1-1 and MAT1-2 partners and environmental conditions, with recombination confirmed utilising molecular markers. This indicated that sexual reproduction might be possible in many supposedly asexual aspergilli and beyond, providing general insights into the nature of asexuality in fungi.National Natural Science Foundation of China 31601446National Research Foundation of Korea 2016010945Intelligent Synthetic Biology Center of Global Frontier Projects 2015M3A6A8065838Biotechnology and Biological Sciences Research CouncilGovernment of IraqMinisterio de Economía y Competitividad BIO2015-67148-

Supporting Accurate Interpretation of Self-Administered Medical Test Results for Mobile Health: Assessment of Design, Demographics, and Health Condition

Background: Technological advances in personal informatics allow people to track their own health in a variety of ways, representing a dramatic change in individuals’ control of their own wellness. However, research regarding patient interpretation of traditional medical tests highlights the risks in making complex medical data available to a general audience. Objective: This study aimed to explore how people interpret medical test results, examined in the context of a mobile blood testing system developed to enable self-care and health management. Methods: In a preliminary investigation and main study, we presented 27 and 303 adults, respectively, with hypothetical results from several blood tests via one of the several mobile interface designs: a number representing the raw measurement of the tested biomarker, natural language text indicating whether the biomarker’s level was low or high, or a one-dimensional chart illustrating this level along a low-healthy axis. We measured respondents’ correctness in evaluating these results and their confidence in their interpretations. Participants also told us about any follow-up actions they would take based on the result and how they envisioned, generally, using our proposed personal health system. Results: We find that a majority of participants (242/328, 73.8%) were accurate in their interpretations of their diagnostic results. However, 135 of 328 participants (41.1%) expressed uncertainty and confusion about their ability to correctly interpret these results. We also find that demographics and interface design can impact interpretation accuracy, including false confidence, which we define as a respondent having above average confidence despite interpreting a result inaccurately. Specifically, participants who saw a natural language design were the least likely (421.47 times, P=.02) to exhibit false confidence, and women who saw a graph design were less likely (8.67 times, P=.04) to have false confidence. On the other hand, false confidence was more likely among participants who self-identified as Asian (25.30 times, P=.02), white (13.99 times, P=.01), and Hispanic (6.19 times, P=.04). Finally, with the natural language design, participants who were more educated were, for each one-unit increase in education level, more likely (3.06 times, P=.02) to have false confidence. Conclusions: Our findings illustrate both promises and challenges of interpreting medical data outside of a clinical setting and suggest instances where personal informatics may be inappropriate. In surfacing these tensions, we outline concrete interface design strategies that are more sensitive to users’ capabilities and conditions

γ-Catenin at Adherens Junctions: Mechanism and Biologic Implications in Hepatocellular Cancer after β-Catenin Knockdown

Abstractβ-Catenin is important in liver homeostasis as a part of Wnt signaling and adherens junctions (AJs), while its aberrant activation is observed in hepatocellular carcinoma (HCC). We have reported hepatocyte-specific β-catenin knockout (KO) mice to lack adhesive defects as γ-catenin compensated at AJ. Because γ-catenin is a desmosomal protein, we asked if its increase in KO might deregulate desmosomes. No changes in desmosomal proteins or ultrastructure other than increased plakophilin-3 were observed. To further elucidate the role and regulation of γ-catenin, we contemplate an in vitro model and show γ-catenin increase in HCC cells upon β-catenin knockdown (KD). Here, γ-catenin is unable to rescue β-catenin/T cell factor (TCF) reporter activity; however, it sufficiently compensates at AJs as assessed by scratch wound assay, centrifugal assay for cell adhesion (CAFCA), and hanging drop assays. γ-Catenin increase is observed only after β-catenin protein decrease and not after blockade of its transactivation. γ-Catenin increase is associated with enhanced serine/threonine phosphorylation and abrogated by protein kinase A (PKA) inhibition. In fact, several PKA-binding sites were detected in γ-catenin by in silico analysis. Intriguingly γ-catenin KD led to increased β-catenin levels and transactivation. Thus, γ-catenin compensates for β-catenin loss at AJ without affecting desmosomes but is unable to fulfill functions in Wnt signaling. γ-Catenin stabilization after β-catenin loss is brought about by PKA. Catenin-sensing mechanism may depend on absolute β-catenin levels and not its activity. Anti-β-catenin therapies for HCC affecting total β-catenin may target aberrant Wnt signaling without negatively impacting intercellular adhesion, provided mechanisms leading to γ-catenin stabilization are spared

Mining and Modeling Database User Access Patterns

Abstract. We present our approach to mining and modeling the behavior of data-base users. In particular, we propose graphic models to capture the database user’s dynamic behavior and focus on applying data mining techniques to the problem of mining and modeling database user behaviors from database trace logs. The experimental results show that our approach can discover and model user behav-iors successfully.

The influence of quintessence on the motion of a binary system in cosmology

We employ the metric of Schwarzschild space surrounded by quintessential matter to study the trajectories of test masses on the motion of a binary system. The results, which are obtained through the gradually approximate approach, can be used to search for dark energy via the difference of the azimuth angle of the pericenter. The classification of the motion is discussed.Comment: 7 pages, 1 figur

On the stability of black hole event horizons

In this work we study a {\it gedanken} experiment constructed in order to test the cosmic censorship hypothesis and the second law of black hole thermo-dynamics. Matter with a negative gravitating energy is imagined added to a near extremal $U(1)$-charged static black hole in Einstein-Maxwell theory. The dynamics of a similar process is studied and the thermo-dynamical properties of the resulting black hole structure is discussed. A new mechanism which stabilizes black hole event horizons is shown to operate in such processes.Comment: 16, grammatical errors corrected and two references adde

ADAM17 and EGFR regulate IL-6 receptor and amphiregulin mRNA expression and release in cigarette smoke-exposed primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD)

Aberrant activity of a disintegrin and metalloprotease 17 (ADAM17), also known as TACE, and epidermal growth factor receptor (EGFR) has been suggested to contribute to chronic obstructive pulmonary disease (COPD) development and progression. The aim of this study was to investigate the role of these proteins in activation of primary bronchial epithelial cells differentiated at the air–liquid interface (ALI-PBEC) by whole cigarette smoke (CS), comparing cells from COPD patients with non-COPD. CS exposure of ALI-PBEC enhanced ADAM17-mediated shedding of the IL-6 receptor (IL6R) and the EGFR agonist amphiregulin (AREG) toward the ba