Endogenous miRNA in the green alga Chlamydomonas regulates gene expression through CDS-targeting

MicroRNAs regulate gene expression as part of the RNA-induced silencing complex, for which the sequence identity of the miRNA provides the specificity to the target messenger RNA and the result is target repression. The mode of repression can be through target cleavage, RNA destabilization and/or decreased translational efficiency. Here, we provide a comprehensive global analysis of the evolutionarily distant unicellular green alga Chlamydomonas reinhardtii to quantify the effects of miRNA on protein synthesis and RNA abundance. We show that, similar to metazoan steady-state systems, endogenous miRNAs in Chlamydomonas can regulate gene-expression both by destabilization of the mRNA and by translational repression. However, unlike metazoan miRNA where target site utilization localizes mainly to 3'UTRs, in Chlamydomonas utilized target sites lie predominantly within coding regions. These results demonstrate the evolutionarily conserved mode of action for miRNAs, but details of the mechanism diverge between plant and metazoan kingdoms.This work was supported by a Balzan Prize award and the European Research Council Advanced Investigator Grant ERC-2013-AdG 340642 TRIBE. B.Y.W.C. was supported by an EMBO long-term postdoctoral fellowship and a Sir Henry Wellcome Fellowship [096082]. D.C.B. is the Royal Society Edward Penley Abraham Research Professor

Vitamin E and selenium plasma concentrations in weanling pigs under field conditions in Norwegian pig herds

BACKGROUND: The status of α-tocopherol (vit E) and selenium (Se) has been shown to influence disease resistance in pigs, and may be important for the health of weanling pigs. METHODS: Plasma levels of both vit E and Se were followed in weanling pigs under field conditions in six Norwegian pig herds. Plasma vit E and Se were measured in 3 sows from each herd and 4 piglets in the litter of each sow at the day before weaning (day -1); and in the same piglets at days 4, 8 and 18 after weaning. RESULTS: Mean plasma vit E was 4.0 μg/ml in the sows and 2.6 μg/ml in the piglets at day -1, fell to 1.6 μg/ml in the weanling pigs at day 4, and remained low. Mean plasma Se was 0.22 μg/g in the sows and 0.08 μg/g in the piglets at day -1, rose to 0.10 μg/g in the weanlings at day 4, and continued rising. CONCLUSION: The results suggest that vit E and Se supplementation to piglets and weanling pigs in Norway may still be suboptimal, but that levels of the two nutrients partially compensate for each other in the weaning period

Predictors of failed attendances in a multi-specialty outpatient centre using electronic databases.

BACKGROUND: Failure to keep outpatient medical appointments results in inefficiencies and costs. The objective of this study is to show the factors in an existing electronic database that affect failed appointments and to develop a predictive probability model to increase the effectiveness of interventions. METHODS: A retrospective study was conducted on outpatient clinic attendances at Tan Tock Seng Hospital, Singapore from 2000 to 2004. 22864 patients were randomly sampled for analysis. The outcome measure was failed outpatient appointments according to each patient's latest appointment. RESULTS: Failures comprised of 21% of all appointments and 39% when using the patients' latest appointment. Using odds ratios from the mutliple logistic regression analysis, age group (0.75 to 0.84 for groups above 40 years compared to below 20 years), race (1.48 for Malays, 1.61 for Indians compared to Chinese), days from scheduling to appointment (2.38 for more than 21 days compared to less than 7 days), previous failed appointments (1.79 for more than 60% failures and 4.38 for no previous appointments, compared with less than 20% failures), provision of cell phone number (0.10 for providing numbers compared to otherwise) and distance from hospital (1.14 for more than 14 km compared to less than 6 km) were significantly associated with failed appointments. The predicted probability model's diagnostic accuracy to predict failures is more than 80%. CONCLUSION: A few key variables have shown to adequately account for and predict failed appointments using existing electronic databases. These can be used to develop integrative technological solutions in the outpatient clinic

Fuzzy Fibers: Uncertainty in dMRI Tractography

Fiber tracking based on diffusion weighted Magnetic Resonance Imaging (dMRI) allows for noninvasive reconstruction of fiber bundles in the human brain. In this chapter, we discuss sources of error and uncertainty in this technique, and review strategies that afford a more reliable interpretation of the results. This includes methods for computing and rendering probabilistic tractograms, which estimate precision in the face of measurement noise and artifacts. However, we also address aspects that have received less attention so far, such as model selection, partial voluming, and the impact of parameters, both in preprocessing and in fiber tracking itself. We conclude by giving impulses for future research

Early intervention for psychotic disorders: Real-life implementation in Hong Kong

Hong Kong is among the first few cities in Asia to have implemented early intervention for psychosis in 2001. Substantial changes in psychosis service have since taken place. We reviewed available outcome data in Hong Kong, with reference to the philosophy of early intervention in psychosis, discussing experience and lessons learned from the implementation process, and future opportunities and challenges. Data accumulated in the past decade provided evidence for the benefits and significance of early intervention programmes: patients under the care of early intervention service showed improved functioning, milder symptoms, and fewer hospitalizations and suicides. Early intervention is more cost-effective compared with standard care. Stigma and misconception remains an issue, and public awareness campaigns are underway. In recent years, a critical mass is being formed, and Hong Kong has witnessed the unfolding of public service extension, new projects and organizations, and increasing interest from the community. Several major platforms are in place for coherent efforts, including the public Early Assessment Service for Young people with psychosis (EASY) programme, the Psychosis Studies and Intervention (PSI) research unit, the independent Hong Kong Early Psychosis Intervention Society (EPISO), the Jockey Club Early Psychosis (JCEP) project, and the postgraduate Psychological Medicine (Psychosis Studies) programme. The first decade of early intervention work has been promising; consolidation and further development is needed on many fronts of research, service and education. © 2012 Elsevier B.V.postprin

Mathematically Gifted Adolescents Have Deficiencies in Social Valuation and Mentalization

Many mathematically gifted adolescents are characterized as being indolent, underachieving and unsuccessful despite their high cognitive ability. This is often due to difficulties with social and emotional development. However, research on social and emotional interactions in gifted adolescents has been limited. The purpose of this study was to observe differences in complex social strategic behaviors between gifted and average adolescents of the same age using the repeated Ultimatum Game. Twenty-two gifted adolescents and 24 average adolescents participated in the Ultimatum Game. Two adolescents participate in the game, one as a proposer and the other as a responder. Because of its simplicity, the Ultimatum Game is an apt tool for investigating complex human emotional and cognitive decision-making in an empirical setting. We observed strategic but socially impaired offers from gifted proposers and lower acceptance rates from gifted responders, resulting in lower total earnings in the Ultimatum Game. Thus, our results indicate that mathematically gifted adolescents have deficiencies in social valuation and mentalization

Bifurcation Boundary Conditions for Switching DC-DC Converters Under Constant On-Time Control

Sampled-data analysis and harmonic balance analysis are applied to analyze switching DC-DC converters under constant on-time control. Design-oriented boundary conditions for the period-doubling bifurcation and the saddle-node bifurcation are derived. The required ramp slope to avoid the bifurcations and the assigned pole locations associated with the ramp are also derived. The derived boundary conditions are more general and accurate than those recently obtained. Those recently obtained boundary conditions become special cases under the general modeling approach presented in this paper. Different analyses give different perspectives on the system dynamics and complement each other. Under the sampled-data analysis, the boundary conditions are expressed in terms of signal slopes and the ramp slope. Under the harmonic balance analysis, the boundary conditions are expressed in terms of signal harmonics. The derived boundary conditions are useful for a designer to design a converter to avoid the occurrence of the period-doubling bifurcation and the saddle-node bifurcation.Comment: Submitted to International Journal of Circuit Theory and Applications on August 10, 2011; Manuscript ID: CTA-11-016

Trends in prevalence, mortality, and disability-adjusted life-years relating to chronic obstructive pulmonary disease in Europe: an observational study of the global burden of disease database, 2001-2019

Introduction Chronic Obstructive Pulmonary Disease (COPD) is associated with significant mortality and well-defined aetiological factors. Previous reports indicate that mortality from COPD is falling worldwide. This study aims to assess the burden of COPD using prevalence, mortality, and disability-adjusted life years (DALYs) between 2001 and 2019 in 28 European countries (the European Union and the United Kingdom). Methods We extracted COPD data from the Global Burden of Disease database based on the International Classification of Diseases versions 10 (J41, 42, 43, 44 and 47). Age-standardised prevalence rates (ASPRs), age-standardised mortality rates (ASMRs), and DALYs were analysed for European countries by sex for each year (2001–2019) and reported per 100,000 population. We used Joinpoint regression analysis to quantify changing trends in the burden of COPD. Results In 2019, the median ASPR across Europe was 3230/100,000 for males and 2202/100,000 for females. Between 2001 and 2019, the median percentage change in ASPR was − 9.7% for males and 4.3% for females. 23/28 countries demonstrated a decrease in ASPRs in males, and 11/28 demonstrated a decrease in females. The median percentage change in ASMR between 2001 and 2019 was − 27.5% for males and − 10.4% for females. 25/28 and 19/28 countries demonstrated a decrease in ASMR in males and females, respectively. Conclusion In the EU between 2001 and 2019 COPD prevalence has overall increased in females but continues to decrease in males and in some countries, female prevalence now exceeds that of males. COPD mortality in the EU has decreased overall between 2001 and 2019; however, this decrease is not universal, particularly in females, and therefore remains a substantial source of amenable mortality