A Novel Graph-Theoretical Approach for Identifying Inter-correlations and Functional Pathways in Microbiome Data

The human microbiome represents a vastly complex ecosystem that is tightly linked to our development. Microbiomes play critical roles in nutrient uptake, immune system development, and vitamin production. The evolution of human microbiomes continues to impact the overall health and quality of life of all humans. For example, despite the ability of microbiota to restrict pathogen invasion, pathogens have evolved tougher due to changes in diets, host environments, and use of antibiotics and other drugs. Such evolution has impacted the organization and composition of the microbial community which, in turn, has influenced susceptibility to and severity of the different type of infections. In fact, the interactions between elements of microbiome significantly shape its host microbial community. Hence, recent metagenomics- based studies of microbiomes has been focusing on how to characterize the composition of species in the microbiome and their co-occurrence patterns. In this study, we propose a comprehensive graph-theoretic framework that integrates microbe-microbe and microbe-host interactions. The study uses microbiome data from Crohn’s disease patients and healthy individuals in a Korean population to develop and test an integrated bioinformatics pipeline. We utilize the integrated pipeline to characterize the taxonomic and metabolic pathway composition in both groups. We show that different groups of bacteria are significantly associated with various phenotypes related to metabolic pathways in patient samples as compared to healthy samples. The obtained results also reveal that microbial elements extracted from within the highly correlated group among Crohn’s disease patients are closely associated with the metabolic mechanisms that have been linked to Crohn’s disease

Mechanisms of paracrine and endocrine actions of Angiotensin II

Adipose tissue expresses high levels of angiotensinogen (agt), the only known precursor of Angiotensin II (Ang II) and we have previously shown that this hormone plays a paracrine role in regulation of adipocyte metabolism by increasing activity and gene expression of two key liogenic enzymes, fatty acid synthase (FAS) and glycerol-3-phosephate dehydrogenase (GPDH). However, molecular mechanisms by which Ang II regulates an adipocyte lipogenic gene, namely FAS and transcription factors mediating this regulation are largely unknown. Furthermore, signaling mechanisms whereby Ang II induces adiposity need to be further explored. Accordingly, our studies were designed to investigate transcriptional regulation of FAS gene by Ang II and determine signaling mechanisms of Ang II leading to activate FAS gene transcription. We demonstrated that Ang II responsive element is an E box within adipocyte FAS gene and the adipocyte determination and differentiation factor1/sterol-regulatory element binding protein 1c (ADD1/SERBP1c) functions as a transcription factor mediating these actions. Ang II induced FAS transcription as well as ADD1 gene expression in a glucose-dependent manner. Using immunoprecipitation and western blot analyses, we found that Ang II regulates adipocyte metabolism via activation of insulin signaling molecules including IRβ, IRS, PI-3K and Akt. This signaling mechanism was mainly mediated by angiotensin receptor type 1 receptors (AT1) and in part by angiotensin receptor type 2 receptors (AT2). Next, with agt knockout (agt -/-, KO) and transgenic (Tg-KO mice expressing agt exclusively in adipose tissue and Tg-WT mice overexpressing agt in adipose tissue) mouse models, we examined changes in adipose tissue metabolism in vivo and renal gene regulation in these mice and further dissected endocrine effects of adipocyte agt. We found that compared with those of WT mice, body weight gain and fat pad weight were lower in response to high fat diet in KO mice exhibiting hypotension and renal abnormalities. Targeted expression of the agt gene only in adipose tissue (Tg-KO) partly rescued these phenotypes whereas agt overexpression in adipose tissue of transgenic mice (Tg-WT) was associated with increased epididymal fat pad mass and blood pressure. Subsequent western blot and renal gene expression analyses indicated that adipocyte agt participates in systemic blood pressure regulation at least partly by increasing renal agt and AT1 receptor production in Tg-WT mice. Additionally, microarray data revealed that adipose tissue-specific agt restoration was able to correct altered expression of genes associated with blood pressure homeostasis and renal function in KO mice. In conclusion, ANG II plays a hypertrophic role in adipocytes by a paracrine/autocrine mechanism. Furthermore, adipocyte Ang II exerts endocrine effects on renal function and gene expression, thereby contributing to systemic blood pressure regulation and kidney homeostasis. This study may provide valuable approaches in treatments of obesity and obesity-associated metabolic alternations such as insulin resistance and hypertension

L1 translation as scaffolding in tutor talk: a case study of two Korean tutors

With the increasing popularity of the communicative approach in the mid-20th century, the use of the L1 was discouraged and stigmatized in foreign language education. Since the emergence of the sociocultural perspective, however, L1 use has been reconsidered as a key mediating tool for second language learning. Utilizing this sociocultural approach, this study examines how L1 translation is used in tutor-tutee talk during writing center appointments by analyzing the talk of two Korean tutors with their seven tutees. The analysis reveals that L1 translation not only helps the tutees clarify their intended meaning in their texts, but also serves as a successful tool for cognitively scaffolding tutee learning—in the forms of pump, hint, and prompt—by helping both the tutor and tutee negotiate meaning and arrive at a solution together. The results bring new insights regarding the use of L1 translation in tutor and tutee interaction by highlighting the usefulness of L1 translation as scaffolding for language learners, particularly when their language proficiency is not advanced. This study implies that the use of L1, in particular, L1 translation may contribute to L2 learners’ learning of English by facilitating their negotiations of meaning with their teachers as to finally arrive at mutual understanding of each other

Genetic Manipulations of PPARs: Effects on Obesity and Metabolic Disease

The interest in genetic manipulations of PPARs is as old as their discovery as receptors of ligands with beneficial clinical activities. Considering the effects of PPAR ligands on critical aspects of systemic physiology, including obesity, lipid metabolism, insulin resistance, and diabetes, gene knockout (KO) in mice is the ideal platform for both hypothesis testing and discovery of new PPAR functions in vivo. With the fervent pursuit of the magic bullet to eradicate the obesity epidemic, special emphasis has been placed on the impacts of PPARs on obesity and its associated diseases. As detailed in this review, understanding how PPARs regulate gene expression and basic metabolic pathways is a necessary intermediate en route to deciphering their effects on obesity. Over a decade and dozens of genetic modifications of PPARs into this effort, valuable lessons have been learned, but we are left with more questions to be answered. These lessons and future prospects are the subject of this review

Laccases for enzymatic colouration of unbleached cotton

The concept presented in this paper is the utilisation of the natural flavonoids present in cotton as anchors to attach other phenolic compounds to the fiber surface. Laccase can catalyze the oxidation of flavonoids in solution producing quinones that can be further polymerised and grafted onto surface of the cotton providing yellow to brown colouration, depending on the external flavonoids used and on the reaction conditions. Factors such as temperature, time of reaction, pretreatment of cotton, mechanical agitation and the role of an organic solvent were studied in order to improve this laccase colouration reaction. After dyeing, colour measurements and fastness tests (washing, friction and weathering fastness) were performed. A strong mechanical agitation, an increased reaction temperature (from 30 to 50 °C), and the addition of an organic solvent improved dyeing. The natural flavonoids present on cotton were found to play an important role on the grafting reaction, improving dyeing and colour fastness. Since the traditional bleaching pretreatment of cotton removes these natural flavonoids from cotton, the proposed laccase colouration reaction could be carried out without a previous bleaching treatment resulting in a more environmentally friendly process

Deficit of Hot Dust in Low-redshift Active Galactic Nuclei

We assemble a broad-band spectral energy distribution (SED) ranging from optical to mid-infrared of nearby active galactic nuclei at $z < 0.4$. SED fitting analysis is performed using semi-empirical templates derived from Palomar-Green quasars to classify the sample into normal, warm-dust-deficient (WDD), and hot-dust-deficient (HDD) AGNs. Kolmogorov-Smirnov tests reveal that HDD AGNs exhibit, on average higher AGN luminosity than normal and WDD AGNs. HDD fraction, on the other hand, is only weakly correlated with black hole mass and inversely correlated with Eddington ratio. By fixing the other parameters, we conclude that the HDD fraction is primarily connected with the AGN luminosity. It implies that there is a causal connection between the covering factor of the hot dust component and AGN luminosity, possibly due to the sublimation of the innermost dust or the thickening of the intervening gas in the broad-line region. Analysis of the outflow properties traced by the wing of [O III]$\lambda5007$ suggests that outflows may be related to the formation and maintenance of the hot dust component. Finally, we demonstrate through comparison with previous studies that the classification of HDD AGNs requires careful subtraction of the host galaxy light.Comment: Accepted for publication in Ap

The Structure Function of Mid-infrared Variability in Low-redshift Active Galactic Nuclei

Using the multi-epoch mid-infrared (MIR) photometry from the Wide-field Infrared Survey Explorer spanning a baseline of $\sim10$ yr, we extensively investigate the MIR variability of nearby active galactic nuclei (AGNs) at $0.15 < z < 0.4$. We find that the ensemble structure function in the W1 band ($3.4\ \mu$m) can be modeled with a broken power law. Type 1 AGNs tend to exhibit larger variability amplitudes than type 2 AGNs, possibly due to the extinction by the torus. The variability amplitude is inversely correlated with the AGN luminosity, consistent with a similar relation known in the optical. Meanwhile, the slope of the power law increases with AGN luminosity. This trend can be attributed to the fact that the inner radius of the torus is proportional to the AGN luminosity, as expected from the size$-$luminosity relation of the torus. Interestingly, low-luminosity type 2 AGNs, unlike low-luminosity type 1 AGNs, tend to exhibit smaller variability amplitude than do high-luminosity AGNs. We argue that either low-luminosity type 2 AGNs have distinctive central structures due to their low luminosity or their MIR brightness is contaminated by emission from the cold dust in the host galaxy. Our findings suggest that the AGN unification scheme may need to be revised. We find that the variability amplitude of dust-deficient AGNs is systematically larger than that of normal AGNs, supporting the notion that the hot and warm dust in dust-deficient AGNs may be destroyed and reformed according to the strength of the ultraviolet radiation from the accretion disk.Comment: Accepted for publication in ApJ, 17 pages, 13 figure

A Mid-infrared Flare in the Seyfert Galaxy NGC 3786: A Changing-look Event Triggered by an Obscured Tidal Disruption Event?

We report an exceptional mid-infrared flare in the Seyfert 1.8 NGC 3786. In the multi-epoch data from the Wide-field Infrared Survey Explorer, the nuclear mid-infrared brightness of NGC 3786 appears to vary substantially up to $0.5-0.8$ mag around mid-2020. However, there is no evidence of significant variation in the corresponding light curve of the optical band from the Zwicky Transient Facility. This implies that the flare may have been heavily obscured by nuclear dust. Through follow-up spectroscopic observations with Gemini-North after the flare, we find that broad emission lines in ${\rm Pa}\alpha$ and ${\rm Pa}\beta$ newly appear, while the broad ${\rm H}\beta$ emission is marginally detected in the post-flare spectrum. In addition, their central wavelengths are systematically redshifted up to 900 km s$^{-1}$ with respect to the narrow emission lines. This reveals that the flare is associated with the changing-look phenomenon from type 1.8 to type 1. Based on these findings, we argue that the flare is likely to originate from an obscured tidal disruption event, although extreme variation in the accretion rate may not be ruled out completely.Comment: Accepted to Ap