Do RCAN1 proteins link chronic stress with neurodegeneration?

It has long been suspected that chronic stress can exacerbate, or even cause, disease. We now propose that the RCAN1 gene, which can generate several RCAN1 protein isoforms, may be at least partially responsible for this phenomenon. We review data showing that RCAN1 proteins can be induced by multiple stresses, and present new data also implicating psychosocial/emotional stress in RCAN1 induction. We further show that transgenic mice overexpressing the RCAN1-1L protein exhibit accumulation of hyperphosphorylated tau protein (AT8 antibody), an early precursor to the formation of neurofibrillary tangles and neurodegeneration of the kind seen in Alzheimer disease. We propose that, although transient induction of the RCAN1 gene might protect cells against acute stress, persistent stress may cause chronic RCAN1 overexpression, resulting in serious side effects. Chronically elevated levels of RCAN1 proteins may promote or exacerbate various diseases, including tauopathies such as Alzheimer disease. We propose that the mechanism by which stress can lead to these diseases involves the inhibition of calcineurin and the induction of GSK-3 beta by RCAN1 proteins. Both inhibition of calcineurin and induction of GSK-3 beta contribute to accumulation of phosphorylated tau, formation of neurofibrillary tangles, and eventual neurodegeneration.-Ermak, G., Pritchard, M. A., Dronjak, S., Niu, B., Davies, K. J. A. Do RCAN1 proteins link chronic stress with neurodegeneration? FASEB J. 25, 3306-3311 (2011). www.fasebj.or

Detecting click fraud in online advertising: A data mining approach

National Research Foundation (NRF) Singapore under International Research Centres in Singapore Funding InitiativeSubmit request for dataset at https://larc.smu.edu.sg/buzzcity-mobile-advertisement-dataset</p

Expression of Cathepsins B, D, and G in WHO Grade I Meningioma

Aim: We have recently demonstrated the presence of putative tumor stem cells (TSCs) in World Health Organization (WHO) grade I meningioma (MG) localized to the microvessels, which expresses components of the renin-angiotensin system (RAS). The RAS is known to be dysregulated and promotes tumorigenesis in many cancer types, including glioblastoma. Cathepsins B, D, and G are isoenzymes that catalyze the production of angiotensin peptides, hence providing bypass loops for the RAS. This study investigated the expression of cathepsins B, D, and G in WHO grade I MG in relation to the putative TSC population we have previously demonstrated.Methods: 3,3-Diaminobenzidine (DAB) immunohistochemical (IHC) staining with antibodies for cathepsins B, D, and G was performed on WHO grade I MG tissue samples from 10 patients. Three of the MG samples subjected to DAB IHC staining underwent immunofluorescence (IF) IHC staining to investigate co-expression of each of these cathepsins using combinations of smooth muscle actin (SMA) and embryonic stem cell marker OCT4. NanoString mRNA expression (n = 6) and Western blotting (WB; n = 5) analyses, and enzyme activity assays (EAAs; n = 3), were performed on snap-frozen WHO grade I MG tissue samples to confirm transcriptional activation, protein expression, and functional activity of these proteins, respectively.Results: DAB IHC staining demonstrated expression of cathepsins B, D, and G in all 10 MG samples. NanoString mRNA expression and WB analyses showed transcriptional activation and protein expression of all three cathepsins, although cathepsin G was expressed at low levels. EAAs demonstrated that cathepsin B and cathepsin D were functionally active. IF IHC staining illustrated localization of cathepsin B and cathepsin D to the endothelium and SMA+ pericyte layer of the microvessels, while cathepsin G was localized to cells scattered within the interstitium, away from the microvessels.Conclusion: Cathepsin B and cathepsin D, and to a lesser extent cathepsin G, are expressed in WHO grade I MG. Cathepsin B and cathepsin D are enzymatically active and are localized to the putative TSC population on the microvessels, whereas cathepsin G was localized to cells scattered within the interstitium, These results suggest the presence of bypass loops for the RAS, within WHO grade I MG

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Memories at the margins : Chinese-educated intellectuals in Singapore

Abstract not available

Insight into the Council on Governance of Institutes of Public Character's recommendations.

The aim of this paper is to help reader to better understand the rationale behind the Code and to help deal with the common implementation problems faced by IPCs. The focus of this paper will be on board governance, conflict of interest, financial management and control and disclosure and transparency

Networking or competition: Singapore companies' alliances in China

125 p.This research was embarked upon to examine the alliances of Singaporean business when making foreign direct investments in China. Specifically, investigations were focused on determining the existence of an empirical relationship between the perceptions of Sino-Singaporean joint venture success and management issues, in particular commitment, control and conflicts. The study was concerned solely on the views and interests of the Singaporean parent. During the course of this research, relevant literature on the subjects were reviewed to highlight the theories involved and to design the questionnaire. The questionnaires were then administered through the local postal mail system.ACCOUNTANC

Preliminary study - an adventure centre at Pulau Ubin.

This preliminary study seeks to examine the potential of developing an Adventure Centre at Pulau Ubin. The primary target for the proposed centre is the individual visitor segment, while the school and company segment will serve as secondary segments for the centre. The findings suggest sufficient interest among the three segments and we would thus, propose a more indepth study to confirm the more detailed aspects for the establishment of such a centre

Active control of low-frequency noise through a single top-hung window in a full-sized room

The push for greater urban sustainability has increased the urgency of the search for noise mitigation solutions that allow for natural ventilation into buildings. Although a viable active noise control (ANC) solution with up to 10 dB of global attenuation between 100 Hz and 1000 Hz was previously developed for an open window, it had limited low-frequency performance below 300 Hz, owing to the small loudspeakers used. To improve the low-frequency attenuation, four passive radiator-based speakers were affixed around the opening of a top-hung ventilation window. The active control performance between 100 Hz and 700 Hz on a single top-hung window in a full-sized mock-up apartment room was examined. Active attenuation came close to the performance of the passive insulation provided by fully closing the window for expressway traffic and motorbike passing noise types. For a jet aircraft flyby, the performance of active attenuation with the window fully opened was similar to that of passive insulation with fully closed windows. In the case of low-frequency compressor noise, active attenuation's performance was significantly better than the passive insulation. Overall, between 8 dB and 12 dB of active attenuation was achieved directly in front of the window opening, and up to 10.5 dB of attenuation was achieved across the entire room.Ministry of National Development (MND)National Research Foundation (NRF)Published versionThis research is supported by the Singapore Ministry of National Development and the National Research Foundation, Prime Minister’s Office under the Cities of Tomorrow (CoT) Research Programme (CoT Award No.COT-V4-2019-1). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not reflect the views of the Singapore Ministry of National Development and National Research Foundation, Prime Minister’s Office, Singapore