The Role of Notch Signalling on Heart Rate and Atrial Conduction Velocity

From the Washington University Office of Undergraduate Research Digest (WUURD), Vol. 12, 05-01-2017. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Lindsey Paunovich, Editor; Helen Human, Programs Manager and Assistant Dean in the College of Arts and Sciences Mentor: Stacey Rentschle

The Role of Notch Signaling on Heart Rate and Atrial Conduction

Heart disease is the leading cause of death worldwide and can result in arrhythmias, or dysregulation in the electrical activation of the heart. Sick Sinus Syndrome (SSS) is characterized by sinus bradycardia (slowed heart rate, HR), slowed conduction through atrial myocardium, and can predispose to the development of atrial fibrillation. A developmental signaling pathway, Notch, regulates cellular identity through differentiation of cardiomyocytes (CMs) into cardiac conduction system-like cells. Previous data show that Notch electrically remodels the right atrium, causing slowed conduction velocity (CV) and hallmarks of SSS including sinus pauses, sinus bradycardia and a predisposition to atrial fibrillation. However, the molecular mechanisms behind these phenotypes are not known. We hypothesized that Notch activation produces slowed CV through downregulation of major cardiac voltage-gated sodium channel (NaV1.5) and atrial gap junction (Connexin40, Cx40). A “Tet-On” doxycycline-activated system using transgenic adult mice was used to activate Notch specifically in CMs. We assayed various determinants of CV, including fibrosis, cellular hypertrophy, and Na+ channel and gap junction expression. Trichrome stain and hydroxyproline assay indicated normal levels of non-conductive fibroblasts. To determine whether Notch activation is associated with pathophysiological hypertrophy, I quantified cell area using immunohistochemistry and found no difference in Notch activated hearts when compared with controls. Furthermore, immunohistochemistry indicated no gross changes in NaV1.5 or Cx40 expression within the atrial myocardium. However, localization of NaV1.5 and Cx40 within the plasma membranes of CMs, as well as post-translational modifications that may result in slowed conduction velocity are yet to be analyzed. Future studies will determine whether Notch-induced slowed HR is due to autonomous changes within the pace-making sinus node (SAN) region or non-autonomous changes within the atrial myocardium. Notch will be activated specifically in the SAN of the adult mouse heart using an HCN4-creER tamoxifen-inducible system and HR will be evaluated using electrocardiograms

Simultaneous immunization with Omp25 and L7/L12 provides protection against brucellosis in mice

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Chamber-specific transcriptional responses in atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, yet the molecular signature of the vulnerable atrial substrate is not well understood. Here, we delineated a distinct transcriptional signature in right versus left atrial cardiomyocytes (CMs) at baseline and identified chamber-specific gene expression changes in patients with a history of AF in the setting of end-stage heart failure (AF+HF) that are not present in heart failure alone (HF). We observed that human left atrial (LA) CMs exhibited Notch pathway activation and increased ploidy in AF+HF but not in HF alone. Transient activation of Notch signaling within adult CMs in a murine genetic model is sufficient to increase ploidy in both atrial chambers. Notch activation within LA CMs generated a transcriptomic fingerprint resembling AF, with dysregulation of transcription factor and ion channel genes, including Pitx2, Tbx5, Kcnh2, Kcnq1, and Kcnip2. Notch activation also produced distinct cellular electrophysiologic responses in LA versus right atrial CMs, prolonging the action potential duration (APD) without altering the upstroke velocity in the left atrium and reducing the maximal upstroke velocity without altering the APD in the right atrium. Our results support a shared human/murine model of increased Notch pathway activity predisposing to AF

The factors influencing consumer buying behavior in Indian Civil Aviation Industry

V dnešním vysoce konkurenčním a náročném světě, letecké společnosti se snaží získat podíl na trhu a udržet jejich ziskovost. Snaží se přijít s novými a originálními způsoby, jak přilákat zákazníky na svou stranu a to nikdy nebylo tak složité v tomto světě moderních informačních a komunikačních technologií. V tomto článku se pokusím zhodnotit z hlediska indického cestujícího to, co je potřeba zvážit před nákupním rozhodnutím. Cílem této studie je, které režimy zákazníci skutečně preferují a jaké nabídky nebo služby poskytované leteckými společnostmi lákají zákazníky nejvíce. Tato studie ukazuje, jak velký význam indický cestující dává bezpečnosti, dochvilnosti, propagaci, image atd. Také je ve studii zahrnutých několik doporučení na základě marketingových, komunikačních a informačně technologických pokrocích pro letecké společnosti, jak být úspěšný na vysoce konkurenčním indickém trhu.In today's fiercely competitive and demanding world, the airlines are struggling to gain market share and sustain their profitability. They are trying to come up with new and unique ways to lure customers over to their side instead of their competitors and it has never been so complicated in this world of advanced information and communication technologies.In this paper I try to evaluate from an Indian passengers point of view that which are the things they consider before making a buying decision. The aim of this study is to which schemes the customers really prefer and what offers or services provided by the airlines attract customers the most. This study shows how much importance an Indian passenger gives to safety, punctuality, promotions, image etc. Also Included in the study are some recommendations based on marketing, communication and information technological advancements for the airlines to be successful in the highly competitive and demanding Indian market

Role of microalgae as a sustainable alternative of biopolymers and its application in industries

The escalating accumulation of petroleum-based polymers has depleted resources and raised environmental concerns due to their non-recyclable and non-biodegradable nature. Consequently, there has been a growing interest in bio-based plastics, particularly algal-based biopolymers, which offer recyclability and eco-friendliness. Algae-derived polymers have distinct advantages, such as autotrophic growth reducing greenhouse gas emissions, rapid growth rate, low nutritional requirements, and resilience to harsh environments. Additionally, algae exhibit higher photosynthetic potential (10-20%) compared to terrestrial plants (1%-2%). The range of algal-derived polymers includes alginate, laminarin, fucoidan, carrageenan, agar, ulvan, polyhydroxyalkanoates (PHA), and poly-(Hydroxybutyrate) (PHB). However, further efforts are required to implement them on a large scale. This review highlights algae's potential as a raw material for biopolymer production, exploring their characteristics and applications in diverse industries like food and pharmaceuticals