Differential Gene Expression and Adherence of Escherichia coli O157:H7 In Vitro and in Ligated Pig Intestines

BACKGROUND: Escherichia coli O157:H7 strain 86-24 grown in MacConkey broth (MB) shows almost no adherence to cultured epithelial cells but adheres well in pig ligated intestines. This study investigated the mechanisms associated with the difference between in-vitro and in-vivo adherence of the MB culture. METHODOLOGY/PRINCIPAL FINDINGS: It was found that decreased adherence in vitro by bacteria grown in MB was mainly due to lactose, possibly implicating the involvement of carbon catabolite repression (CCR). Expression of selected virulence-related genes associated with adherence and CCR was then examined by quantitative PCR. When bacteria were grown in MB and Brain Heart Infusion with NaHCO(3) (BHIN) plus lactose, pH was reduced to 5.5-5.9 and there was a significant decrease in expression of the locus of enterocyte effacement (LEE) genes eae, tir, espD, grlA/R and ler, and an increase in cya (cAMP), and two negative regulators of the LEE, gadE and hfq. Putative virulence genes stcE, hlyA, ent and nleA were also decreased in vitro. Reversal of these changes was noted for bacteria recovered from the intestine, where transcripts for qseF and fis and putative virulence factors AidA(15), TerC and Ent/EspL2 were significantly increased, and transcripts for AIDA(48), Iha, UreC, Efa1A, Efa1B, ToxB, EhxA, StcE, NleA and NleB were expressed at high levels. CONCLUSIONS/SIGNIFICANCE: Presence of lactose resulted in decreased expression of LEE genes and the failure of EHEC O157:H7 to adhere to epithelial cells in vitro but this repression was overcome in vivo. CCR and/or acidic pH may have played a role in repression of the LEE genes. Bacterial pathogens need to integrate their nutritional metabolism with expression of virulence genes but little is known of how this is done in E. coli O157:H7. This study indicates one aspect of the subject that should be investigated further

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

The effect of familiarity on older adults’ engagement in exergames

With entertaining game graphics and tasks, exergames can provide benefits for older adults to effectively exercise their physical and mental capabilities. However, it is sometimes difficult for exergames to engage older adults due to maladaptation. In this work, we suggest that the feeling of familiarity can positively influence older adult’s adaptation to exergames. Based on this intuition, to help exercise older adult’s upper limbs, we design a Ping Pong Exergame (PPE) infused with table tennis activities, which has been shown to be one of the most popular (thus familiar) sports among Singaporean older adults. A five-week study involving 44 Singaporean older adults shows that the participants who have higher levels of familiarity to table tennis exhibit higher motivation and ability in playing PPE, which indicate that familiarity can improve older adults’ adaptation to exergames.NRF (Natl Research Foundation, S’pore)MOH (Min. of Health, S’pore)Accepted versio

Risk factors for pulmonary embolism after hip and knee arthroplasty: a population-based study

Pulmonary embolism (PE) is a cause of death after total hip and knee arthroplasty (THA, TKA). We characterised the patient population suffering from in-hospital PE and identified perioperative risk factors associated with PE using nationally representative data. Data from the National Hospital Discharge Survey between 1990 and 2004 on patients who underwent primary or revision THA/TKA in the United States were analysed. Multivariate regression analysis was performed to determine if perioperative factors were associated with increased risk of in-hospital PE. An estimated 6,901,324 procedures were identified. The incidence of in-hospital PE was 0.36%. Factors associated with an increased risk for the diagnosis of PE included: revision THA, female gender, dementia, obesity, renal and cerebrovascular disease. An increased association with PE was found among patients with diagnosis of Adult Respiratory Distress Syndrome (ARDS), psychosis (confusion), and peripheral thrombotic events. Our findings may be useful in stratifying the individual patient’s risk of PE after surgery