Moderate mutation rate in the SARS coronavirus genome and its implications

BACKGROUND: The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood. RESULTS: Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 – 2.38 × 10(-3 )nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 – 3.30 × 10(-3 )and 1.67 – 4.67 × 10(-3 )per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002. CONCLUSIONS: The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic

Genetic variation at twentythree microsatellite loci in sixteen human populations

Artículo científico -- Universidad de Costa Rica, Instituto de Investigaciones en Salud. 1999We have analysed genetic variation at 23 microsatellite loci in a global sample of 16 ethnically and geographically diverse human populations. On the basis of their ancestral heritage and geographic locations, the studied populations can be divided into five major groups, viz. African, Caucasian, Asian Mongoloid, American Indian and Pacific Islander. With respect to the distribution of alleles at the 23 loci, large variability exists among the examined populations. However, with the exception of the American Indians and the Pacific Islanders, populations within a continental group show a greater degree of similarity. Phylogenetic analyses based on allele frequencies at the examined loci show that the first split of the present-day human populations had occurred between the Africans and all of the non-African populations, lending support to an African origin of modern human populations. Gene diversity analyses show that the coefficient of gene diversity estimated from the 23 loci is, in general, larger for populations that have remained isolated and probably of smaller effective sizes, such as the American Indians and the Pacific Islanders. These analyses also demonstrate that the component of total gene diversity, which is attributed to variation between groups of populations, is significantly larger than that among populations within each group. The empirical data presented in this work and their analyses reaffirm that evolutionary histories and the extent of genetic variation among human populations can be studied using microsatellite loci.Universidad de Costa Rica. Instituto de Investigaciones en SaludUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Implications of Deferred Revenue Changes for Future Financial Performance and Market Underreaction

This study found that changes in current deferred revenues (ΔDRC) are positively associated with sales growth, gross profit margin, profit margin and return on assets of the next two years. The evidence suggests that deferred revenue changes can serve as a valid leading indicator for a firm’s future financial performance. It also identified a positive relationship between a firm’s ΔDRC and its market valuation, indicating that market participants (at least partially) incorporate the future performance implications of deferred revenue changes into their valuation decisions. While prior research suggested mismatch of revenues and expenses (Prakash and Sinha 2013) as the potential explanation for the abnormal stock returns in reporting firms, the empirical evidence in this study supports an alternative explanation: investors’ underreaction to the information content of deferred revenue changes

The Deregulatory Effects of the Telecommunications Act of 1996 on the Broadcasting Industry: Expectations vs. Reality

The broadcasting industry experienced drastic deregulation with the passage of the Telecommunications Act of 1996. This study examines the capital market reactions to the passage of the Act and aftermath changes in profitability and efficiency in the broadcasting industry. This study finds that the deregulation. particularly relaxing the rules for broadcast ownership. had significant positive effects on stock returns for the broadcasting firms. Among them, firms focusing on broadcasting business and small television groups gained more from the deregulation in terms of increases in market value, as opposed to diversified and large television groups. The longitudinal analysis indicates that the profitability of broadcasting firms in terms of return on sales improved after the Act. This can mainly be attributed to broadcasting firm\u27s increased market power that resulted from increased industry concentration. Profitability in terms of return on assets, however, deteriorated after the Act. which can be attributed to decreased operating efficiency represented by asset turnover. We find no evidence that the deregulation improved the broadcasting industry\u27s efficiency of employees to generate sales. Our findings question the notion that the deregulation would help the industry to improve its operating efficiency by achieving economies of scale

Chief Executive Compensation and Institutional Ownership

In this study the impact of institutional ownership is explored on the structure of CEO compensation. Evidences indicate that large increases in institutional ownership significantly reduce the level of CEO compensation and compensation risk. However, no significant evidence shows that the CEO pay-for-performance sensitivity is affected by institutional holdings

The deregulatory effects of the Telecommunications Act of 1996 on the broadcasting industry: Expectations vs. reality

The broadcasting industry experienced drastic deregulation with the passage of the Telecommunications Act of 1996. This study examines the capital market reactions to the passage of the Act and aftermath changes in profitability and efficiency in the broadcasting industry. This study finds that the deregulation, particularly relaxing the rules for broadcast ownership, had significant positive effects on stock returns for the broadcasting firms. Among them, firms focusing on broadcasting business and small television groups gained more from the deregulation in terms of increases in market value, as opposed to diversified and large television groups. The longitudinal analysis indicates that the profitability of broadcasting firms in terms of return on sales improved after the Act. This can mainly be attributed to broadcasting firm's increased market power that resulted from increased industry concentration. Profitability in terms of return on assets, however, deteriorated after the Act, which can be attributed to decreased operating efficiency represented by asset turnover. We find no evidence that the deregulation improved the broadcasting industry's efficiency of employees to generate sales. Our findings question the notion that the deregulation would help the industry to improve its operating efficiency by achieving economies of scale.

The Varlability of Board Size Determinants: An Empirical Analysis

We use a sample of randomly selected CRSP-listed firms to explore the cross-sectional determinants of corporate board size. We find that the average number of directors on boards differs significantly across industries. Further evidence indicates that these differences are jointly and significantly determined by a variety of director, CEO, ownership, and firm-specific variables across industries. The determinants of board size also vary substantially across surviving and delistingfirms, regulated and unregulated companies, firms in financial distress, and bankrupt firms. Our models explain as much as 52% ofthe observed variation in board size. The cross-sectional variation in board size is driven by various economic forces. Therefore, understanding the choice of board structure requires a thorough examination ofthe associated costs and benefits for individual firms. [G30, G32, G33, G34

Molecular Mechanism of Action of Cycloxaprid, An Oxabridged <i>cis</i>-Nitromethylene Neonicotinoid

Cycloxaprid, an oxabridged cis-nitromethylene neonicotinoid, showed high insecticidal activity in Hemipteran insect pests. In this study, the action of cycloxaprid was characterized by recombinant receptor Nlα1/rβ2 and cockroach neurons. On Nlα1/β2 in Xenopus oocytes, cycloxaprid acted as a full agonist. The imidacloprid resistance-associated mutation Y151S reduced the Imax of cycloxaprid by 37.0% and increased EC50 values by 1.9-fold, while the Imax of imidacloprid was reduced by 72.0%, and EC50 values increased by 2.3-fold. On cockroach neurons, the maximum currents elicited by cycloxaprid were only 55% of that of acetylcholine, a full agonist, but with close EC50 values of that of trans-neonicotinoids. In addition, cycloxaprid inhibited acetylcholine-evoked currents on insect neurons in a concentration-dependent manner when co-applied with acetylcholine. Cycloxaprid at low concentrations significantly inhibited the activation of nAChRs by acetylcholine, and its inhibition potency at 1 µM was higher than its activation potency on insect neurons. Two action potencies, activation, and inhibition, by cycloxaprid on insect neurons provided an explanation for its high toxicity to insect pests. In summary, as a cis-nitromethylene neonicotinoid, cycloxaprid showed high potency on both recombinant nAChR Nlα1/β2 and cockroach neurons, which guaranteed its high control effects on a variety of insect pests

Identification of Candidate Genes Associated with Yak Body Size Using a Genome-Wide Association Study and Multiple Populations of Information

Yaks have evolved several breeds or genetic resources owing to their geographical and ecological environment, and investigating the genetic construction of body size among breeds is key for breeding. Here, a genome-wide association study (GWAS) was performed for five body size traits in 31 yak breeds and genetic resources. The information from clustering individuals according to their habitats was used for kinship grouping in the compressed mixed linear model (CMLM). We named this approach the pCMLM method. A total of 3,584,464 high-quality single nucleotide polymorphisms (SNPs) were obtained, and six markers were found to be significantly associated with height by pCMLM. Four candidate genes, including FXYD6, SOHLH2, ADGRB2, and OSBPL6, were identified. Our results show that when CMLM cannot identify optimal clustering groups, pCMLM can provide sufficient associated results based on population information. Moreover, this study provides basic information on the gene localization of quantitative traits of body size among yak breeds

Correction: Protocatechuic aldehyde acts synergistically with dacarbazine to augment DNA double-strand breaks and promote apoptosis in cutaneous melanoma cells

An amendment to this paper has been published and can be accessed via the original article