The Role of Simple Rules in the Conduct of Canadian Monetary Policy

The third strategy employed by the Bank when dealing with uncertainty is the consideration of appropriate simple reaction functions or "rules" for the setting of the policy interest rate. Since John Taylor's presentation of his much-discussed rule, research on simple policy rules has exploded. Simple rules have several advantages. In particular, they are easy to construct and communicate and are believed by some to be robust, in the sense of generating good results in a variety of economic models. This article provides an overview of the recent research regarding the usefulness and robustness of simple monetary policy rules, particularly in models of the Canadian economy. It also describes and explains the role of simple rules in the conduct of monetary policy in Canada.

A Novel Redox Regulator, MnTnBuOE-2-PyP\u3csup\u3e5+\u3c/sup\u3e, Enhances Normal Hematopoietic Stem/Progenitor Cell Function

The signaling of reactive oxygen species (ROS) is essential for the maintenance of normal cellular function. However, whether and how ROS regulate stem cells are unclear. Here, we demonstrate that, in transgenic mice expressing the human manganese superoxide dismutase (MnSOD) gene, a scavenger of ROS in mitochondria, the number and function of mouse hematopoietic stem/progenitor cells (HSPC) under physiological conditions are enhanced. Importantly, giving MnTnBuOE-2-PyP5+(MnP), a redox- active MnSOD mimetic, to mouse primary bone marrow cells or to C57B/L6 mice significantly enhances the number of HSPCs. Mechanistically, MnP reduces superoxide to hydrogen peroxide, which activates intracellular Nrf2 signaling leading to the induction of antioxidant enzymes, including MnSOD and catalase, and mitochondrial uncoupling protein 3. The results reveal a novel role of ROS signaling in regulating stem cell function, and suggest a possible beneficial effect of MnP in treating pathological bone marrow cell loss and in increasing stem cell population for bone marrow transplantation

Cognitive Reserve and Mild Cognitive Impairment

Background and Objectives Little is known about the effect of education or other indicators of cognitive reserve on the rate of reversion from mild cognitive impairment (MCI) to normal cognition (NC) or the relative rate (RR) of reversion from MCI to NC vs progression from MCI to dementia. Our objectives were to (1) estimate transition rates from MCI to NC and dementia and (2) determine the effect of age, APOE, and indicators of cognitive reserve on the RR of reversion vs progression using multistate Markov modeling. Methods We estimated instantaneous transition rates between NC, MCI, and dementia after accounting for transition to death across up to 12 assessments in the Nun Study, a cohort study of religious sisters aged 75+ years. We estimated RRs of reversion vs progression for age, APOE, and potential cognitive reserve indicators: education, academic performance (high school grades), and written language skills (idea density, grammatical complexity). Results Of the 619 participants, 472 were assessed with MCI during the study period. Of these 472, 143 (30.3%) experienced at least one reverse transition to NC, and 120 of the 143 (83.9%) never developed dementia (mean follow-up = 8.6 years). In models adjusted for age group and APOE, higher levels of education more than doubled the RR ratio of reversion vs progression. Novel cognitive reserve indicators were significantly associated with a higher adjusted RR of reversion vs progression (higher vs lower levels for English grades: RR ratio = 1.83; idea density: RR ratio = 3.93; and grammatical complexity: RR ratio = 5.78). Discussion Knowledge of frequent reversion from MCI to NC may alleviate concerns of inevitable cognitive decline in those with MCI. Identification of characteristics predicting the rate of reversion from MCI to NC vs progression from MCI to dementia may guide population-level interventions targeting these characteristics to prevent or postpone MCI and dementia. Research on cognitive trajectories would benefit from incorporating predictors of reverse transitions and competing events, such as death, into statistical modeling. These results may inform the design and interpretation of MCI clinical trials, given that a substantial proportion of participants may experience improvement without intervention

Control of cortex development by ULK4, a rare risk gene for mental disorders including schizophrenia

This work was supported by the grants from British Council China (Sino-UK higher Education for PhD studies) to Y.D. and C.D.M., and also from the following funding resources: Tenovus Scotland (G12/05, B.L.), The Carnegie Trust (RG13060-10, B.L.) and National Natural Science Foundation of China (91232724, Y.D.; 31100788, L.Z.; 81200933, N.N.S.; 31528011, B.L. and Y.D.).Peer reviewedPublisher PD

A SURF4-to-proteoglycan relay mechanism that mediates the sorting and secretion of a tagged variant of sonic hedgehog

SignificanceSonic Hedgehog (Shh) is a key signaling molecule that plays important roles in embryonic patterning, cell differentiation, and organ development. Although fundamentally important, the molecular mechanisms that regulate secretion of newly synthesized Shh are still unclear. Our study reveals a role for the cargo receptor, SURF4, in facilitating export of Shh from the endoplasmic reticulum (ER) via a ER export signal. In addition, our study provides evidence suggesting that proteoglycans promote the dissociation of SURF4 from Shh at the Golgi, suggesting a SURF4-to-proteoglycan relay mechanism. These analyses provide insight into an important question in cell biology: how do cargo receptors capture their clients in one compartment, then disengage at their destination?</p

The Size and Culturability of Patient-Generated SARS-CoV-2 Aerosol

BACKGROUND: Aerosol transmission of COVID-19 is the subject of ongoing policy debate. Characterizing aerosol produced by people with COVID-19 is critical to understanding the role of aerosols in transmission. OBJECTIVE: We investigated the presence of virus in size-fractioned aerosols from six COVID-19 patients admitted into mixed acuity wards in April of 2020. METHODS: Size-fractionated aerosol samples and aerosol size distributions were collected from COVID-19 positive patients. Aerosol samples were analyzed for viral RNA, positive samples were cultured in Vero E6 cells. Serial RT-PCR of cells indicated samples where viral replication was likely occurring. Viral presence was also investigated by western blot and transmission electron microscopy (TEM). RESULTS: SARS-CoV-2 RNA was detected by rRT-PCR in all samples. Three samples confidently indicated the presence of viral replication, all of which were from collected sub-micron aerosol. Western blot indicated the presence of viral proteins in all but one of these samples, and intact virions were observed by TEM in one sample. SIGNIFICANCE: Observations of viral replication in the culture of submicron aerosol samples provides additional evidence that airborne transmission of COVID-19 is possible. These results support the use of efficient respiratory protection in both healthcare and by the public to limit transmission