Forceful patterning in mouse preimplantation embryos.

The generation of a functional organism from a single, fertilized ovum requires the spatially coordinated regulation of diverse cell identities. The establishment and precise arrangement of differentiated cells in developing embryos has, historically, been extensively studied by geneticists and developmental biologists. While chemical gradients and genetic regulatory networks are widely acknowledged to play significant roles in embryo patterning, recent studies have highlighted that mechanical forces generated by, and exerted on, embryos are also crucial for the proper control of cell differentiation and morphogenesis. Here we review the most recent findings in murine preimplantation embryogenesis on the roles of cortical tension in the coupling of cell-fate determination and cell positioning in 8-16-cell-stage embryos. These basic principles of mechanochemical coupling in mouse embryos can be applied to other pattern formation phenomena that rely on localized modifications of cell polarity proteins and actin cytoskeletal components and activities.

ImaEdge - a platform for quantitative analysis of the spatiotemporal dynamics of cortical proteins during cell polarization.

Cell polarity involves the compartmentalization of the cell cortex. The establishment of cortical compartments arises from the spatial bias in the activity and concentration of cortical proteins. The mechanistic dissection of cell polarity requires the accurate detection of dynamic changes in cortical proteins, but the fluctuations of cell shape and the inhomogeneous distributions of cortical proteins greatly complicate the quantitative extraction of their global and local changes during cell polarization. To address these problems, we introduce an open-source software package, ImaEdge, which automates the segmentation of the cortex from time-lapse movies, and enables quantitative extraction of cortical protein intensities. We demonstrate that ImaEdge enables efficient and rigorous analysis of the dynamic evolution of cortical PAR proteins during Caenorhabditis elegans embryogenesis. It is also capable of accurate tracking of varying levels of transgene expression and discontinuous signals of the actomyosin cytoskeleton during multiple rounds of cell division. ImaEdge provides a unique resource for quantitative studies of cortical polarization, with the potential for application to many types of polarized cells.This article has an associated First Person interview with the first authors of the paper.

Determination of Cost-Effectiveness Threshold for Health Care Interventions in Malaysia.

BACKGROUND: One major challenge in prioritizing health care using cost-effectiveness (CE) information is when alternatives are more expensive but more effective than existing technology. In such a situation, an external criterion in the form of a CE threshold that reflects the willingness to pay (WTP) per quality-adjusted life-year is necessary. OBJECTIVES: To determine a CE threshold for health care interventions in Malaysia. METHODS: A cross-sectional, contingent valuation study was conducted using a stratified multistage cluster random sampling technique in four states in Malaysia. One thousand thirteen respondents were interviewed in person for their socioeconomic background, quality of life, and WTP for a hypothetical scenario. RESULTS: The CE thresholds established using the nonparametric Turnbull method ranged from MYR12,810 to MYR22,840 (~US $4,000-US $7,000), whereas those estimated with the parametric interval regression model were between MYR19,929 and MYR28,470 (~US $6,200-US $8,900). Key factors that affected the CE thresholds were education level, estimated monthly household income, and the description of health state scenarios. CONCLUSIONS: These findings suggest that there is no single WTP value for a quality-adjusted life-year. The CE threshold estimated for Malaysia was found to be lower than the threshold value recommended by the World Health Organization.

A balance between antagonizing PAR proteins specifies the pattern of asymmetric and symmetric divisions in C. elegans embryogenesis.

Coordination between cell differentiation and proliferation during development requires the balance between asymmetric and symmetric modes of cell division. However, the cellular intrinsic cue underlying the choice between these two division modes remains elusive. Here, we show evidence in Caenorhabditis elegans that the invariable lineage of the division modes is specified by the balance between antagonizing complexes of partitioning-defective (PAR) proteins. By uncoupling unequal inheritance of PAR proteins from that of fate determinants during cell division, we demonstrate that changes in the balance between PAR-2 and PAR-6 can be sufficient to re-program the division modes from symmetric to asymmetric and vice versa in two daughter cells. The division mode adopted occurs independently of asymmetry in cytoplasmic fate determinants, cell-size asymmetry, and cell-cycle asynchrony between sister cells. We propose that the balance between PAR proteins represents an intrinsic self-organizing cue for the specification of the two division modes during development.

Protective effect of aqueous extract from Spirulina platensis against cell death induced by free radicals.

BACKGROUND: Spirulina is a commercial alga well known to contain various antioxidants, especially phycocyanin. Apart from being sold as a nutraceutical, Spirulina is incorporated as a functional ingredient in food products and beverages. Most of the previous reports on antioxidant activity of Spirulina were based on chemical rather than cell-based assays. The primary objective of this study was to assess the antioxidant activity of aqueous extract from Spirulina based on its protective effect against cell death induced by free radicals. METHODS: The antioxidant activity of the cold water extract from food-grade Spirulina platensis was assessed using both chemical and cell-based assays. In the cell-based assay, mouse fibroblast cells (3T3) cells were incubated for 1 h in medium containing aqueous extract of Spirulina or vitamin C (positive control) at 25, 125 and 250 µg/mL before the addition of 50 µM 1,1-diphenyl-2-picrylhydrazyl (DPPH) or 3-ethylbenzothiazoline-6-sulfonic acid (ABTS). The cells were incubated for another 24 h before being assessed for cell death due to apoptosis using the Cell Death Detection ELISA Kit. Spectrophotometric assays based on DPPH and ABTS were also used to assess the antioxidant activity of the extract compared to vitamin C and vitamin E (positive controls). RESULTS: Spirulina extract did not cause cytotoxic effect on 3T3 cells within the range of concentrations tested (0 - 250 µg/mL). The extract reduced significantly (p < 0.05) apoptotic cell death due to DPPH and ABTS by 4 to 5-fold although the activity was less than vitamin C. Based on the DPPH assay, the radical scavenging activity of the extract was higher than phycocyanin and was at least 50% of vitamin C and vitamin E. Based on the ABTS assay, the antioxidant activity of the extract at 50 µmug/mL was as good as vitamin C and vitamin E. CONCLUSIONS: The results showed that aqueous extract of Spirulina has a protective effect against apoptotic cell death due to free radicals. The potential application of incorporating Spirulina into food products and beverages to enhance their antioxidant capacity is worth exploring.

The fate of the new pharmacy bill: going backwards or forwards?

BACKGROUND: The proposed Pharmacy Bill of Malaysia which served to consolidate and harmonise the existing pharmacy legislation which has been used for more than 60 years. This new Pharmacy Bill contains 17 parts and a total of 170 legislative sections covering laws governing pharmacy practice, medicinal products classification, registration, sale, supply, licensing etc. Our article could serve as a case study on pharmacy jurisprudence and drug regulation as well as the governance for medicines. DISCUSSION: Changes to the colonial era legislation are long overdue as the present pharmaceutical and medical controls are not integrated and various overlaps exist in terms of roles of control. However, various organisations of private general practitioners strongly opposed this Pharmacy Bill and lobbied for a revised version that greatly favours themselves. Thus, the latest revision of this Pharmacy Bill renders the power to medical doctors to not only continue selling and supplying medications but also compound medication. SUMMARY: A complete overhaul of pharmacy legislation in view of the current challenges faced in providing efficient and comprehensive health services in Malaysia is necessary. For the sake of patients' safety and good governance for medicines, the private general practitioners should empower the patients with their needs for prescription and itemised billing. The proposed Pharmacy Bill could make the whole mechanism of managing and controlling the use of medicines more transparent and synchronised.

Exploring the willingness to pay for a quality-adjusted life-year in the state of Penang, Malaysia.

INTRODUCTION: The incremental cost-effectiveness ratio (ICER) is typically compared with a reference value to support the cost-effectiveness of a decision. One method for estimating this value is to estimate the willingness-to-pay (WTP) for a quality-adjusted life-year (QALY). This study was conducted to explore the WTP for a QALY in the Malaysian population. METHODS: A cross-sectional, contingent valuation study was conducted in Penang, Malaysia. Respondents were selected from randomly chosen geographical grids of Penang. Respondents' sociodemographic information, qualities of life, and WTP for one additional QALY were collected using predesigned questionnaires in face-to-face interviews. WTP values were elicited using a double-bound dichotomous choice via a bidding game approach. The Heckman selection model was applied to the analysis of the mean WTP/QALY values, where the "protest zero" values, which may contribute to selection bias, were excluded. RESULTS: The mean value of WTP for an additional QALY gained was estimated to be MYR (Malaysian Ringgit) 29,080 (~USD 9,000). Key factors that affected the WTP include ethnicity and estimated monthly household income. CONCLUSION: The study findings suggested that the cost-effectiveness threshold value as studied in Penang, Malaysia was estimated to be MYR 29,080.