The Evolution and Functional Significance of Nested Gene Structures in Drosophila melanogaster

Nearly ten percent of the genes in the genome of Drosophila melanogaster are in nested structures, in which one gene is completely nested within the intron of another gene (nested and including gene, respectively). Even though the coding sequences and UTRs of these nested/including gene pairs do not overlap, their intimate structures and the possibility of shared regulatory sequences raise questions about the evolutionary forces governing the origination, and subsequent functional and evolutionary impacts of these structures. In this study, we show that nested genes experience weaker evolutionary constraint, have faster rates of protein evolution and are expressed in fewer tissues than other genes, while including genes show the opposite patterns. Surprisingly, despite completely overlapping with each other, nested and including genes are less likely to display correlated gene expression and biological function than the nearby yet non-overlapping genes. Interestingly, significantly fewer nested genes are transcribed from the same strand as the including gene. We found that same-strand nested genes are more likely to be single-exon genes. In addition, same-strand including genes are less likely to have known lethal or sterile phenotypes than opposite-strand including genes only when the corresponding nested genes have introns. These results support our hypothesis that selection against potential erroneous mRNA splicing when nested and including genes are on the same strand plays an important role in the evolution of nested gene structures

Genomic variation and evolution of the human malaria parasite Plasmodium falciparum

Malaria is a deadly disease that causes nearly one million deaths each year. Understanding the demographic history of the malaria parasite Plasmodium falciparum and the genetic basis of its adaptations to antimalarial treatments and the human immune system is important for developing methods to control and eradicate malaria. To study the long-term demographic history and recent effective size of the population in order to identify genes under selection more efficiently and predict the effectiveness of selection, in Chapter 2 we sequenced the complete genomes of 25 cultured P. falciparum isolates from Senegal. In addition, in Chapter 3 we estimated temporal allele frequencies in 24 loci among 528 strains from the same population across six years. Based on genetic diversity of the genome sequences, we estimate the long-term effective population size to be approximately 100,000, and a major population expansion of the parasite population approximately 20,000-40,000 years ago. Based on temporal changes in allele frequencies, however, the recent effective size is estimated to be less than 100 from 2007-2011. The discrepancy may reflect recent aggressive efforts to control malaria in Senegal or migration between populations

Quantified movement test of core muscles for Athletes

The purpose of this study was to compare the different of the core muscles ability between normal subjects and athletes of an assessment consisted of seven movement tests. Nineteen participants were voluntarily recruited in this study and divided into normal subjects (N=9, age=20.2+-0.7 y/o, weight:63.7+-11.7 kg, height:170.9+-6.7 cm) and collegiate athletes (N=10, age=19.9+-1.0 y/o, weight; 72.4+-7.8 kg, height; 172.5+-4.5 cm). The result shows that the path length of plank, bird dog with right-hand raise, bird dog with left-hand raise, right side plank, right bridge, left bridge and area of right bridge, left bridge has significant differences between two groups (Table 1). Athletes exhibit shorter path length and smaller path area in all of these data

The Distribution of Pairwise Genetic Distances: A Tool for Investigating Disease Transmission

Whole-genome sequencing of pathogens has recently been used to investigate disease outbreaks and is likely to play a growing role in real-time epidemiological studies. Methods to analyze high-resolution genomic data in this context are still lacking, and inferring transmission dynamics from such data typically requires many assumptions. While recent studies have proposed methods to infer who infected whom based on genetic distance between isolates from different individuals, the link between epidemiological relationship and genetic distance is still not well understood. In this study, we investigated the distribution of pairwise genetic distances between samples taken from infected hosts during an outbreak. We proposed an analytically tractable approximation to this distribution, which provides a framework to evaluate the likelihood of particular transmission routes. Our method accounts for the transmission of a genetically diverse inoculum, a possibility overlooked in most analyses. We demonstrated that our approximation can provide a robust estimation of the posterior probability of transmission routes in an outbreak and may be used to rule out transmission events at a particular probability threshold. We applied our method to data collected during an outbreak of methicillin-resistant Staphylococcus aureus, ruling out several potential transmission links. Our study sheds light on the accumulation of mutations in a pathogen during an epidemic and provides tools to investigate transmission dynamics, avoiding the intensive computation necessary in many existing methods

Discovering recent selection forces shaping the evolution of dengue viruses based on polymorphism data across geographic scales

Incomplete selection makes it challenging to infer selection on genes at short time scales, especially for microorganisms, due to stronger linkage between loci. However, in many cases, the selective force changes with environment, time, or other factors, and it is of great interest to understand selective forces at this level to answer relevant biological questions. We developed a new method that uses the change in d(N)/d(S), instead of the absolute value of d(N)/d(S), to infer the dominating selective force based on sequence data across geographical scales. If a gene was under positive selection, d(N)/d(S) was expected to increase through time, whereas if a gene was under negative selection, d(N)/d(S) was expected to decrease through time. Assuming that the migration rate decreased and the divergence time between samples increased from between-continent, within-continent different-country, to within-country level, d(N)/d(S) of a gene dominated by positive selection was expected to increase with increasing geographical scales, and the opposite trend was expected in the case of negative selection. Motivated by the McDonald-Kreitman (MK) test, we developed a pairwise MK test to assess the statistical significance of detected trends in d(N)/d(S). Application of the method to a global sample of dengue virus genomes identified multiple significant signatures of selection in both the structural and non-structural proteins. Because this method does not require allele frequency estimates and uses synonymous mutations for comparison, it is less prone to sampling error, providing a way to infer selection forces within species using publicly available genomic data from locations over broad geographical scales.Peer reviewe

Recurrent bottlenecks in the malaria life cycle obscure signals of positive selection

Detecting signals of selection in the genome of malaria parasites is a key to identify targets for drug and vaccine development. Malaria parasites have a unique life cycle alternating between vector and host organism with a population bottleneck at each transition. These recurrent bottlenecks could influence the patterns of genetic diversity and the power of existing population genetic tools to identify sites under positive selection. We therefore simulated the site-frequency spectrum of a beneficial mutant allele through time under the malaria life cycle. We investigated the power of current population genetic methods to detect positive selection based on the site-frequency spectrum as well as temporal changes in allele frequency. We found that a within-host selective advantage is difficult to detect using these methods. Although a between-host transmission advantage could be detected, the power is decreased when compared with the classical Wright– Fisher (WF) population model. Using an adjusted null site-frequency spectrum that takes the malaria life cycle into account, the power of tests based on the site-frequency spectrum to detect positive selection is greatly improved. Our study demonstrates the importance of considering the life cycle in genetic analysis, especially in parasites with complex life cyclesOrganismic and Evolutionary Biolog

α-Lactosylceramide Protects Against iNKT-Mediated Murine Airway Hyperreactivity and Liver Injury Through Competitive Inhibition of Cd1d Binding.

Invariant natural killer T (iNKT) cells, which are activated by T cell receptor (TCR)-dependent recognition of lipid-based antigens presented by the CD1d molecule, have been shown to participate in the pathogenesis of many diseases, including asthma and liver injury. Previous studies have shown the inhibition of iNKT cell activation using lipid antagonists can attenuate iNKT cell-induced disease pathogenesis. Hence, the development of iNKT cell-targeted glycolipids can facilitate the discovery of new therapeutics. In this study, we synthesized and evaluated α-lactosylceramide (α-LacCer), an α-galactosylceramide (α-GalCer) analog with lactose substitution for the galactose head and a shortened acyl chain in the ceramide tail, toward iNKT cell activation. We demonstrated that α-LacCer was a weak inducer for both mouse and human iNKT cell activation and cytokine production, and the iNKT induction by α-LacCer was CD1d-dependent. However, when co-administered with α-GalCer, α-LacCer inhibited α-GalCer-induced IL-4 and IFN-γ production from iNKT cells. Consequently, α-LacCer also ameliorated both α-GalCer and GSL-1-induced airway hyperreactivity and α-GalCer-induced neutrophilia when co-administered in vivo. Furthermore, we were able to inhibit the increases of ConA-induced AST, ALT and IFN-γ serum levels through α-LacCer pre-treatment, suggesting α-LacCer could protect against ConA-induced liver injury. Mechanistically, we discerned that α-LacCer suppressed α-GalCer-stimulated cytokine production through competing for CD1d binding. Since iNKT cells play a critical role in the development of AHR and liver injury, the inhibition of iNKT cell activation by α-LacCer present a possible new approach in treating iNKT cell-mediated diseases

KINEMATIC ANALYSIS OF TENNIS VOLLEY

The purpose of this study was to examine selected kinematic variables of the tennis volley. Fifteen skilled tennis players performed volley strokes under five (right, rightmiddle, middle, left-middle, left) different lateral contact locations. A ball machine was modified so subjects could not predict the ball trajectory before it was released from the machine. Two high-speed cameras (250Hz) were genlocked to collect the data and the Kwon3D software was used to analyze the temporal and kinematic variables. The results indicated the middle location have the shortest pushing (0.249s) and stroke (0.466s) time than other locations. An ipsilateral side step occurred more often in Backhand (BH, 86%) than in Forehand (FH, 67%). In addition, more FH volley (55%) was used than BH (45%) when return the ball from middle location

Mass-accretion, spectral, and photometric properties of T Tauri stars in Taurus based on TESS and LAMOST

We present the analysis of 16 classical T Taur stars using LAMOST and TESS data, investigating spectral properties, photometric variations, and mass-accretion rates. All 16 stars exhibit emissions in H$\alpha$ lines, from which the average mass-accretion rate of $1.76\times10^{-9}~M_{\odot}yr^{-1}$ is derived. Two of the stars, DL Tau and Haro 6-13, show mass-accretion bursts simultaneously in TESS, ASAS-SN, and/or ZTF survey. Based on these observations, we find that the mass-accretion rates of DL Tau and Haro 6-13 reach their maximums of $2.5 \times 10^{-8}~M_{\odot}yr^{-1}$ and $2 \times 10^{-10}~M_{\odot}yr^{-1}$ during the TESS observation, respectively. We detect thirteen flares among these stars. The flare frequency distribution shows that the CTTSs' flare activity is not only dominated by strong flares with high energy but much more active than those of solar-type and young low-mass stars. By comparing the variability classes reported in the literature, we find that the transition timescale between different classes of variability in CTTSs, such as from Stochastic (S) to Bursting (B) or from quasi-periodic symmetric (QPS) to quasi-periodic dipping (QPD), may range from 1.6 to 4 years. We observe no significant correlation between inclination and mass-accretion rates derived from the emission indicators. This suggests that inner disk properties may be more important than that of outer disk. Finally, we find a relatively significant positive correlation between the asymmetric metric "M" and the cold disk inclination compared to the literature. A weak negative correlation between the periodicity metric "Q" value and inclination has been also found.Comment: 39 pages, 22 figures, 8 table

Serum leptin is associated with cardiometabolic risk and predicts metabolic syndrome in Taiwanese adults

<p>Abstract</p> <p>Background</p> <p>Leptin is associated with cardiovascular disease (CVD); however, few studies have assessed its relationship with metabolic syndrome, especially in an Asian population. Therefore, the aim of the present study was to assess leptin levels and evaluate its association with CVD and metabolic syndrome.</p> <p>Methods</p> <p>In 2009, 957 subjects, who underwent a routine physical examination and choose leptin examination, were selected to participate. Participants (269 females and 688 males) were stratified according to leptin level quartiles. Metabolic syndrome was defined by NCEP ATP III using waist circumference cutoffs modified for Asian populations, and CVD risk was determined using the Framingham Heart Study profile.</p> <p>Results</p> <p>Leptin levels were correlated with CVD risk in men and women. With the exception of fasting plasma glucose, increased leptin levels were observed as factors associated with metabolic syndrome increased in both males and females. After adjusting for age, an association between leptin levels and metabolic syndrome was observed. After adjusting for age alone or with tobacco use, subjects in the highest leptin quartile had a higher risk of having metabolic syndrome than those in the lowest quartile (OR = 6.14 and 2.94 for men and women, respectively). After further adjustment for BMI, metabolic syndrome risk remained significantly increased with increasing leptin quartiles in men. Finally, increased leptin levels were a predictor of metabolic syndrome in men and women.</p> <p>Conclusions</p> <p>Serum leptin levels are correlated with CVD risk and metabolic syndrome. Analysis of leptin as part of routine physical examinations may prove beneficial for early diagnosis of metabolic syndrome.</p