Chemically Specific Systematic Coarse-Grained Polymer Model with Both Consistently Structural and Dynamical Properties.

The coarse-grained (CG) model serves as a powerful tool for the simulation of polymer systems; its reliability depends on the accurate representation of both structural and dynamical properties. However, strong correlations between structural and dynamical properties on different scales and also a strong memory effect, enforced by chain connectivity between monomers in polymer systems, render developing a chemically specific systematic CG model a formidable task. In this study, we report a systematic CG approach that combines the iterative Boltzmann inversion (IBI) method and the generalized Langevin equation (GLE) dynamics. Structural properties are ensured by using conservative CG potentials derived from the IBI method. To retrieve the correct dynamical properties in the system, we demonstrate that using a combination of a Rouse-type delta function and a time-dependent short-time kernel in the GLE simulation is practically efficient. The former can be used to adjust the long-time diffusion dynamics, and the latter can be reconstructed from an iterative procedure according to the velocity autocorrelation function (ACF) from all-atomistic (AA) simulations. Taking the polystyrene as an example, we show that not only structural properties of radial distribution function, intramolecular bond, and angle distributions can be reproduced but also dynamical properties of mean-square displacement, velocity ACF, and force ACF resulted from our CG model have quantitative agreement with the reference AA model. In addition, reasonable agreements are observed in other collective properties between our GLE-CG model and the AA simulations as well.

Comparative skin histological and transcriptomic analysis of Rana kukunoris with two different skin colors.

This study compares the skin structures of Rana kukunoris with two different skin colors living in the same area of Haibei in the Northeastern Qinghai-Tibet Plateau. The skin thickness of the khaki R. kukunoris was significantly greater than that of the brown R. kukunoris (P < 0.01), and significantly more mucous and granular glands were present on the dorsal skin of the khaki frog (P < 0.05). Meanwhile, the melanocytes on the dorsal skin of the brown frog were significantly larger than those on the khaki one (P < 0.05). Morphological changes in the expansion and aggregation of melanocytes seemed to deepen the skin color of R. kukunoris. Moreover, transcriptome sequencing identified tyrosine metabolism, melanogenesis, and riboflavin metabolism as the main pathways involved in melanin formation and metabolism in brown R. kukunoris. TYR, MC1R was upregulated as the skin color of R. kukunoris was deepened and contributed to melanin production and metabolism. In contrast, the khaki frog had significantly more upregulated genes and metabolic pathways related to autoimmunity. The khaki frog appeared to defend against ultraviolet (UV) radiation-induced damage by secreting mucus and small molecular peptides, whereas the brown frog protected itself by distributing a large amount of melanin. Hence, the different skin colors of R. kukunoris might represent different adaptation strategies for survival in the intense UV radiation environment of the Qinghai-Tibet Plateau.

Effect of the polar group content on the glass transition temperature of ROMP copolymers.

Polar groups have long been recognized to greatly influence the glass transition temperature (Tg) of polymers, but understanding the underlying physical mechanism remains a challenge. Here, we study the glass formation of ring-opening metathesis polymerization (ROMP) copolymers containing polar groups by employing all-atom molecular dynamics simulations. We show that although the number of hydrogen bonds (NHB) and the cohesive energy density increase linearly as the content of polar groups (fpol) increases, the Tg of ROMP copolymers increases with the increase of fpol in a nonlinear fashion, and tends to plateau for sufficiently high fpol. Importantly, we find that the increase rate of Gibbs free energy for HB breaking gradually slows down with the increase of fpol, indicating that the HB is gradually stabilized. Therefore, Tg is jointly determined by NHB and the strength of HBs in the system, while the latter dominates. Although NHB increases linearly with increasing fpol, the HB strength increases slowly with increasing fpol, which leads to a decreasing rate of increase in Tg.

Research on magneto-hydraulic proportional control strategy for single degree of freedom supporting system of magnetic-liquid double suspension bearing.

Compared with the traditional active electromagnetic bearing, the additional hydrostatic supporting concept is imported to form magnetic-liquid double suspension bearing (MLDSB) without affecting the support performance. Therefore, the bearing carrying capacity and stiffness are greatly increased and the operational stability and reliability of MLDSB are also improved. The controlling strategy and the regulating mode have the major impact on the safe and stable operation of MLDSB, which directly determines the performance quality. MLDSB adopts the magnetic-liquid coupling supporting mode with electromagnetic suspension as the main and hydrostatic supporting as the supplement, which greatly increases the complexity and difficulty of MLDSB. Therefore, the proportional control strategy and the magneto-hydraulic coupled nonlinear controller of MLDSB are explored in this paper. First, the regulation mechanism of the single degree of freedom (DOF) supporting system is revealed, and the proportional-integral-differential controller of the electromagnetic and hydrostatic closed-loop is designed. Then, the fuzzy control idea is introduced into the single DOF supporting system to design a magnetic-liquid variable proportional fuzzy controller, and the difference between the proportional/variable proportional control modes is compared. Finally, the rotor displacement following characteristics and anti-interference characteristics in the proportional/variable proportional control mode are compared on a magnetic-liquid double suspension test bench. The results show that compared with the proportional control method, the variable proportional control method combines the advantages of fast regulation speed of the electromagnetic system and the stable and reliable advantages of the hydrostatic system. In the same step signal, the rotor can achieve unbiased following under two control modes of proportional/variable proportion, and the adjustment time of the variable proportional control mode is shorter. In two control modes, the rotor can be restored to the original equilibrium position. The maximum offset under the variable proportional control mode is smaller, and with the continuous increase of the displacement, the performance of the variable proportional control method is more obvious. The stability control of MLDSB is provided on the theoretical basis in this article.

Lung transcriptome analysis for the identification of genes involved in the hypoxic adaptation of plateau pika (Ochotona curzoniae).

The plateau pika, a typical hypoxia-tolerant mammal lives 3000-5000 m above sea level on the Qinghai-Tibet Plateau, has acquired many physiological and morphological characteristics and strategies in its adaptation to sustained, high-altitude hypoxia. Blunted hypoxic pulmonary vasoconstriction is one such strategy, but the genes involved in this strategy have not been elucidated. Here, we investigated the genes involved and their expression profiles in the lung transcriptome of plateau pikas subjected to different hypoxic conditions (using low-pressure oxygen cabins). A slight, right ventricular hypertrophy was observed in pikas of the control group (altitude: 3200 m) vs. those exposed to 5000 m altitude conditions for one week. Our assembly identified 67,774 genes; compared with their expression in the control animals, 866 and 8364 genes were co-upregulated and co-downregulated, respectively, in pikas subjected to 5000 m altitude conditions for 1 and 4 w. We elucidated pathways that were associated with pulmonary vascular arterial pressure, including vascular smooth muscle contraction, HIF-1 signalling, calcium signalling, cGMP-PKG signalling, and PI3K-Akt signalling based on the differentially expressed genes; the top-100 pathway enrichments were found between the control group and the group exposed to 5000 m altitude conditions for 4 w. The mRNA levels of 18 candidate gene showed that more than 83% of genes were expressed and the number of transcriptome The up-regulated genes were EPAS1, Hbα, iNOS, CX40, CD31, PPM1B, HIF-1α, MYLK, Pcdh12, Surfactant protein B, the down-regulated genes were RYR2, vWF, RASA1, CLASRP, HIF-3α. Our transcriptome data are a valuable resource for future genomic studies on plateau pika.

Multivariate Tail Probabilities: Predicting Regional Pertussis Cases in Washington State.

In disease modeling, a key statistical problem is the estimation of lower and upper tail probabilities of health events from given data sets of small size and limited range. Assuming such constraints, we describe a computational framework for the systematic fusion of observations from multiple sources to compute tail probabilities that could not be obtained otherwise due to a lack of lower or upper tail data. The estimation of multivariate lower and upper tail probabilities from a given small reference data set that lacks complete information about such tail data is addressed in terms of pertussis case count data. Fusion of data from multiple sources in conjunction with the density ratio model is used to give probability estimates that are non-obtainable from the empirical distribution. Based on a density ratio model with variable tilts, we first present a univariate fit and, subsequently, improve it with a multivariate extension. In the multivariate analysis, we selected the best model in terms of the Akaike Information Criterion (AIC). Regional prediction, in Washington state, of the number of pertussis cases is approached by providing joint probabilities using fused data from several relatively small samples following the selected density ratio model. The model is validated by a graphical goodness-of-fit plot comparing the estimated reference distribution obtained from the fused data with that of the empirical distribution obtained from the reference sample only.

Characterization of a complete mitochondrial genome of Turdus ruficollis (Passeriformes: Turdidae).

Turdus ruficollis is mainly found in China and Northeast Asia. So far, the mitochondrial genome of more than 20 species from the genus Turdus has been studied. However, the relevant information of T. ruficollis has not been reported. To grasp a better comprehension on the molecular basis of T. ruficollis, we obtained the complete mitochondrial DNA genome sequences of this species. The mitogenome was 16,737 bp in length, which consists of 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and one control region. A phylogenetic tree based on complete mitogenome sequences revealed that, within the genus Turdidae, T. ruficollis is closely related to T. naumanni and T. eumomus. The complete mitochondrial genome of T. ruficollis would be of great utility for population genetics and phylogeography of the Turdidae family and would also provide meritorious insights for future studies on conservation, genetics, and phylogeny of the Passeriformes family.

The sequence and characterization of mitochondrial of Lepus oiostolus (Lagomorpha: Leporidae).

Lepus oiostolus is widely inhabited in the Qinghai-Tibet Plateau. So far, little mitochondrial genome information of this genus has been described. To grasp a better comprehension on the molecular basis of L. oiostolus, we obtained the complete mitochondrial DNA genome sequences of this species. The mitogenome was 17,320 bp in length, which consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and 1 noncoding regions. The complete mitochondrial genome of L. oiostolus would be of great utility in the phylogenetic analysis of the Lagomorpha and also provide meritorious insights into the deeper problems of the phylogenic analysis.

Biases in Prokaryotic Community Amplicon Sequencing Affected by DNA Extraction Methods in Both Saline and Non-saline Soil.

High-throughput amplicon sequencing technology has been widely used in soil microbiome studies. Here, we estimated the bias of amplicon sequencing data affected by DNA extraction methods in a saline soil, and a non-saline normal soil was used as a control. Compared with the normal soil, several unique points were observed in the saline soil. The soil washing pretreatment can improve not only DNA quantity and quality but also microbial diversities in the saline soil; therefore, we recommend the soil washing pretreatment for saline soils especially hypersaline soils that cannot be achieved with detectable DNA amounts without the pretreatment. Also, evenness indices were more easily affected by DNA extraction methods than richness indices in the saline soil. Moreover, proportions of Gram-positive bacteria had significant positive correlations with the achieved microbial diversities within replicates of the saline soil. Though DNA extraction methods can bias the microbial diversity or community and relative abundances of some phyla/classes can vary by a factor of more than five, soil types were still the most important factor of the whole community. We confirmed good comparability in the whole community, but more attention should be paid when concentrating on an exact diversity value or the exact relative abundance of a certain taxon. Our study can provide references for the DNA extraction from saline and non-saline soils and comparing sequencing data across studies who may employ different DNA extraction methods.

Prokaryotic Community Distribution along an Ecological Gradient of Salinity in Surface and Subsurface Saline Soils.

Salinity effects on microbial communities in saline soils is still unclear, and little is known about subsurface soil microbial communities especially in saline or hypersaline ecosystems. Here we presented the survey of the prokaryotic community in saline soils along a salinity gradient (17.3-148.3 dS/m) in surface (0-10 cm) and subsurface (15-30 cm) saline soils of Qarhan Salt Lake, China. Moreover, we compared them with three paired nonsaline normal soils. Using the high-throughput sequencing technology and several statistical methods, we observed no significant community difference between surface soils and subsurface soils. For environmental factors, we found that TOC was the primary driver of the prokaryotic community distribution in surface saline soils, so was pH in subsurface saline soils. Salinity had more effects on the prokaryotic community in subsurface saline soils than in surface saline soils and played a less important role in saline soils than in saline waters or saline sediments. Our research provided references for the prokaryotic community distribution along a salinity gradient in both surface and subsurface saline soils of arid playa areas.

Microsatellite Loci Analysis Reveals Post-bottleneck Recovery of Genetic Diversity in the Tibetan Antelope.

The Tibetan antelope (chiru, Pantholops hodgsoni) is one of the most endangered mammals native to the Qinghai-Tibetan Plateau. The population size has rapidly declined over the last century due to illegal hunting and habitat damage. In the past 10 years, the population has reportedly been expanding due to conservation efforts. Several lines of evidence suggest that the Tibetan antelope has undergone a demographic bottleneck. However, the consequences of the bottleneck on genetic diversity and the post-bottleneck genetic recovery remain unknown. In this study, we investigate the genetic variation of 15 microsatellite loci from two Tibetan antelope populations sampled in 2003 (Pop2003) and 2013 (Pop2013). A higher level of genetic diversity (NA, 13.286; He, 0.840; PIC, 0.813; I, 2.114) was detected in Pop2013, compared to Pop2003 (NA, 12.929; He, 0.818; PIC, 0.789; I, 2.033). We observe that despite passing through the bottleneck, the Tibetan antelope retains high levels of genetic diversity. Furthermore, our results show significant or near significant increases in genetic diversity (He, PIC and I) in Pop2013 compared with Pop2003, which suggests that protection efforts did not arrive too late for the Tibetan antelope.

Signatures of functional constraint at Fgfr1a Genes in schizothoracine fishes (Pisces: Cypriniformes): The dermal skeleton variation adapted to high-altitude environments.

Fishes harbor a huge resource of phenotypic diversity and are useful for understanding the genetic basis of morphological variation. However, it is difficult to transfer classical genetic mapping to most non-model species. In this study, we performed a comparative sequence analysis of Fgfr1a to first interpret the evolution of this candidate scale-loss gene in 15 schizothoracine fishes with various scale phenotypes. While considerable amino acid (AA) substitutions were observed, molecular evolution analysis indicates that the overall coding regions were subject to functional constraint. We also identified extra copies of Fgfr1a in 4 scale-loss fishes and detected accelerated evolution in one AA substitution specific to these duplicates. We speculate that Fgfr1a had accumulated mutations in the ancestral lineage of scale-loss schizothoracine fishes before experiencing duplication events, which was further followed by the diversification of species. In silico mutation analysis predicted deleterious effects of the mutations while no disruptive molecular mechanism was detected. Collectively, our results highlight the important role of Fgfr1a gene in the adaptive evolution of schizothoracine fishes during their radiation in the Qinghai-Tibetan Plateau.

The complete mitochondrial genome sequence of Platypharodon extremus (Cypriniformes: Cyprinidae).

Platypharodon extemus is a monotypic species of Schizothoracine fishes and it was listed as Endangered species in the "China Red Data Book (Pisces)", Vulnerable (V) by the National Environmental Protection Agency and Endangered Species Scientific Commission. So far, little mitochondrial genome information of this genus has been described. In this study, we obtained the complete mitochondrial DNA genome sequences of this species. The mitogenome was 16,668 bp in length, which consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes and 2 noncoding regions. The base composition of this mitochondrial genome was 28.6% A, 27.3% T, 18.2% G, 25.9% C, with a high A + T content (55.9%). The complete mitochondrial genome of P. extremus would be of great utility in the phylogenetic analysis of the schizothoracine fishes and also provide meritorious insights into the deeper problems of the phylogenic analysis.

Inhibition of inducible nitric oxide synthase expression and nitric oxide production in plateau pika (Ochotona curzoniae) at high altitude on Qinghai-Tibet Plateau.

Nitric oxide (NO), a potent vasodilator, plays an important role in preventing hypoxia induced pulmonary hypertension. Endogenous NO is synthesized by nitric oxide synthases (NOSs) from l-arginine. In mammals, three different NOSs have been identified, including neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Plateau pika (Ochotona curzoniae) is a typical hypoxia tolerant mammal that lives at 3000-5000 m above sea level on the Qinghai-Tibet Plateau. The aim of this study was to investigate whether NOS expression and NO production are regulated by chronic hypoxia in plateau pika. Quantitative real-time PCR and western blot analyses were conducted to quantify relative abundances of iNOS and eNOS transcripts and proteins in the lung tissues of plateau pikas at different altitudes (4550, 3950 and 3200 m). Plasma NO metabolites, nitrite/nitrate (NO(x)⁻) levels were also examined by Ion chromatography to determine the correlation between NO production and altitude level. The results revealed that iNOS transcript levels were significantly lower in animals at high altitudes (decreased by 53% and 57% at altitude of 3950 and 4550 m compared with that at 3200 m). Similar trends in iNOS protein abundances were observed (26% and 41% at 3950 and 4550 m comparing with at 3200 m). There were no significant differences in eNOS mRNA and protein levels in the pika lungs among different altitudes. The plasma NO(x)⁻ levels of the plateau pikas at high altitudes significantly decreased (1.65±0.19 µg/mL at 3200 m to 0.44±0.03 µg/mL at 3950 m and 0.24±0.01 µg/mL at 4550 m). This is the first evidence describing the effects of chronic hypoxia on NOS expression and NO levels in the plateau pika in high altitude adaptation. We conclude that iNOS expression and NO production are suppressed at high altitudes, and the lower NO concentration at high altitudes may serve crucial roles for helping the plateau pika to survive at hypoxic environment.