Viewing Airbnb from Twitter: factors associated with users’ utilization.

Airbnb is a peer-to-peer accommodation website in the sharing economy. Past studies have examined the factors associated with Airbnb utilization from various platforms, but not exclusively from Twitter. A total of 21,097 tweets was collected in a period of two months, and the tweets were qualitatively analyzed with the help of text analysis tools to verify the discourse of discussion. Literature was reviewed for common factors attracting clients to an Airbnb accommodation. Factors were then qualitatively analyzed and compiled using Wmatrix, and the themes that emerged were: Price and status, social interaction and communication, location, reputation, amenities and a pet-friendly environment. This result provides a deeper insight to Airbnb hosts to strategize and add value to their current market situations

Phosphoinositide 3-kinase δ regulates membrane fission of Golgi carriers for selective cytokine secretion

The PI3K isoform p110δ is required for TNF trafficking and secretion

Exosomal microRNAs in the development of essential hypertension and its potential as biomarkers

MicroRNAs (miRNAs) are small regulatory molecules that are involved in posttranscriptional modifications. These noncoding RNAs are usually ferried by extracellular carriers such as exosomes or other protein and lipid carriers inside a range of body fluids including plasma and urine. Due to their ability to withstand harsh external conditions, exosomal miRNAs possess enormous potential as noninvasive disease biomarkers for, notably hypertension, whereby exosomal miRNAs have been implicated in its pathophysiological processes. More importantly, alterations in the microenvironment as a result of disease progression can induce active and selective loading of miRNAs into exosomes. In this paper, we first review the mechanisms of miRNA loading into exosomes, followed by the roles of exosomal miRNAs in the development of hypertension, and the potentials of exosomal miRNAs as biomarkers in comparison with other free circulating miRNAs. Finally, challenges and future research surrounding exosomal miRNAs will also be discussed. This review will aid in the understanding of noninvasive biomarkers for the early diagnosis of hypertension and for probing therapeutic efficacy

Distinct 'Immuno-Allertypes' of Disease and High Frequencies of Sensitisation in Non-Cystic-Fibrosis Bronchiectasis

Rationale: Allergic sensitization is associated with poor clinical outcomes in asthma, chronic obstructive pulmonary disease, and cystic fibrosis; however, its presence, frequency, and clinical significance in non–cystic fibrosis bronchiectasis remain unclear. Objectives: To determine the frequency and geographic variability that exists in a sensitization pattern to common and specific allergens, including house dust mite and fungi, and to correlate such patterns to airway immune-inflammatory status and clinical outcomes in bronchiectasis. Methods: Patients with bronchiectasis were recruited in Asia (Singapore and Malaysia) and the United Kingdom (Scotland) (n = 238), forming the Cohort of Asian and Matched European Bronchiectasis, which matched recruited patients on age, sex, and bronchiectasis severity. Specific IgE response against a range of common allergens was determined, combined with airway immune-inflammatory status and correlated to clinical outcomes. Clinically relevant patient clusters, based on sensitization pattern and airway immune profiles (“immunoallertypes”), were determined. Measurements and Main Results: A high frequency of sensitization to multiple allergens was detected in bronchiectasis, exceeding that in a comparator cohort with allergic rhinitis (n = 149). Sensitization was associated with poor clinical outcomes, including decreased pulmonary function and more severe disease. “Sensitized bronchiectasis” was classified into two immunoallertypes: one fungal driven and proinflammatory, the other house dust mite driven and chemokine dominant, with the former demonstrating poorer clinical outcome. Conclusions: Allergic sensitization occurs at high frequency in patients with bronchiectasis recruited from different global centers. Improving endophenotyping of sensitized bronchiectasis, a clinically significant state, and a “treatable trait” permits therapeutic intervention in appropriate patients, and may allow improved stratification in future bronchiectasis research and clinical trials.Ministry of Education (MOE)Ministry of Health (MOH)National Medical Research Council (NMRC)Published versionSupported by the Singapore Ministry of Health’s National Medical Research Council under its Transition Award NMRC/TA/0048/2016 (S.H.C.) and Changi General Hospital Research grant CHF2016.03-P (T.B.L.). The work performed at NUS was supported by the Singapore Ministry of Education Academic Research Fund, SIgN, and National Medical Research Council grants N-154-000-038-001, R-154-000-404-112, R-154-000-553-112, R-154-000-565-112, R-154-000-630-112, R-154-000-A08-592, R-154-000-A27-597, SIgN-06-006, SIgN-08-020, and NMRC/1150/2008 (F.T.C.); J.D.C. is supported by the GSK/British Lung Foundation Chair of Respiratory Research

Investigating the Role of Phosphoinositide 3-Kinase in Cytokine Trafficking and Secretion

Cytokines are secreted by cells of the immune system to coordinate immune responses. Lipopolysaccharide (LPS) activation of macrophages elicits the de novo biosynthesis and secretion of inflammatory cytokines, including tumor necrosis factor-α (TNF). TNF is an early-response, proinflammatory cytokine with essential roles in immunity; but paradoxically, excessive secretion of TNF has clinically important sequelae in inflammatory diseases, such as rheumatoid arthritis. Whilst the physiological effects of TNF and many other cytokines are well known, we have only begun to understand the intracellular trafficking pathways that lead to their secretion. Yet, these pathways potentially harbor molecular targets that could rationalize new avenues for control of cytokines in disease. Previous efforts from this laboratory have chartered the key organelles for constitutive trafficking of TNF to the macrophage cell surface and have set the stage for this PhD project, which further investigates the molecules and carriers involved in TNF trafficking and secretion. Based on very preliminary data at the outset, this project has focused on exploring the involvement of PIs and PI 3-kinases (PI3Ks) in TNF trafficking. The PI3K family and their products are classically involved in signal transduction, and evidence to support their regulation in constitutive secretory pathways were minimal at the beginning of the study. A central goal of this thesis was to investigate a role for PI3K in the secretory pathway of TNF. Initial studies surveyed the distribution of different phosphoinositides (PIs) on the subcellular membranes in macrophages. By expression of various fluorescent PI-binding modules as probes, results in Chapter 3 provide the first map of PIs associated with macrophage organelles. Our findings also suggest candidate PIs with possible physiological roles in TNF trafficking. In a series of investigations using PI3K broad-spectrum and isoform-selective inhibitors, small-interfering RNAs, and genetic inactivation in mice, the class I PI3K p110δ was identified as the predominant isoform in regulating TNF trafficking and secretion. Ablation of p110δ function selectively blocked the secretion of TNF and accumulated the cytokine at the trans-Golgi network (TGN). These findings led to the use of live-cell imaging to study tubular carriers emerging from the TGN for TNF transport. It was then also revealed that LPS acutely induces the recruitment of p110δ to the Golgi membranes where it is kinase active. Furthermore, this activity of p110δ was shown to be essential for dynamic fission of membrane tubules carrying TNF at the TGN. These findings in Chapter 4 have not only provided the first demonstration of a class I PI3K and its activity at the Golgi, but also excitingly unravelled p110δ as a new component of tubule-fission machinery at the TGN. Finally, work was extended beyond these novel discoveries to explore the influence of p110δ activity in fission of different tubular carriers at the TGN and their roles in cargo export. TNF exits the TGN in tubules that were identified by the GRIP-golgin p230, but not those demarked by golgin-97. By comparing the requirement of p110δ activity in fission of these TGN GRIP tubules, data in Chapter 5 have revealed a selectivity of p110δ for fission of p230 tubules, but not golgin-97 tubules. Preliminary studies with a soluble IL-6 and other cargo shed light on cargo-sorting at the TGN and the selectivity of tubular carriers and their fission machinery. Overall, this thesis provides evidence to support a role for PI3K p110δ in TNF trafficking and secretion. A new function for p110δ in fission of a selective set of tubular carriers for TNF at the TGN is revealed. In a broader view, findings from this work have highlighted the potential of p110δ inhibition as a means to modulate TNF secretion in the future in treatment of inflammatory diseases

Recurrent candidaemia in a neonate with Hirschsprung’s disease: fluconazole resistance and genetic relatedness of eight Candida tropicalis isolates

The incidence of candidaemia among immunocompromised patients in Malaysia is increasing at an alarming rate. Isolation of clinical strains that are resistant to fluconazole has also risen markedly. We report here the repeated isolation of Candida tropicalis from the blood of a neonatal patient with Hirschsprung's disease. In vitro fluconazole susceptibility tests of the eight isolates obtained at different time points showed that seven of the isolates were resistant and one isolate was scored as susceptible dose-dependent. Random amplification of polymorphic DNA fingerprinting of the isolates using three primers and subsequent phylogenetic analysis revealed that these isolates were highly similar strains having minor genetic divergence, with a mean pairwise similarity coefficient of 0·893±0·041. The source of the infectious agent was thought to be the central venous catheter, as culture of its tip produced fluconazole-resistant C. tropicalis. This study demonstrates the utility of applying molecular epidemiology techniques to complement traditional mycological culture and drug susceptibility tests for accurate and appropriate management of recurrent candidaemia and highlights the need for newer antifungals that can combat the emergence of fluconazole-resistant C. tropicalis strains

Inactivation of the Class II PI3K-C2β Potentiates Insulin Signaling and Sensitivity

In contrast to the class I phosphoinositide 3-kinases (PI3Ks), the organismal roles of the kinase activity of the class II PI3Ks are less clear. Here, we report that class II PI3K-C2β kinase-dead mice are viable and healthy but display an unanticipated enhanced insulin sensitivity and glucose tolerance, as well as protection against high-fat-diet-induced liver steatosis. Despite having a broad tissue distribution, systemic PI3K-C2β inhibition selectively enhances insulin signaling only in metabolic tissues. In a primary hepatocyte model, basal PI3P lipid levels are reduced by 60% upon PI3K-C2β inhibition. This results in an expansion of the very early APPL1-positive endosomal compartment and altered insulin receptor trafficking, correlating with an amplification of insulin-induced, class I PI3K-dependent Akt signaling, without impacting MAPK activity. These data reveal PI3K-C2β as a critical regulator of endosomal trafficking, specifically in insulin signaling, and identify PI3K-C2β as a potential drug target for insulin sensitization