Dynamic evolution of bitter taste receptor genes in vertebrates

<p>Abstract</p> <p>Background</p> <p>Sensing bitter tastes is crucial for many animals because it can prevent them from ingesting harmful foods. This process is mainly mediated by the bitter taste receptors (T2R), which are largely expressed in the taste buds. Previous studies have identified some T2R gene repertoires, and marked variation in repertoire size has been noted among species. However, the mechanisms underlying the evolution of vertebrate T2R genes remain poorly understood.</p> <p>Results</p> <p>To better understand the evolutionary pattern of these genes, we identified 16 T2R gene repertoires based on the high coverage genome sequences of vertebrates and studied the evolutionary changes in the number of T2R genes during birth-and-death evolution using the reconciled-tree method. We found that the number of T2R genes and the fraction of pseudogenes vary extensively among species. Based on the results of phylogenetic analysis, we showed that T2R gene families in teleost fishes are more diverse than those in tetrapods. In addition to the independent gene expansions in teleost fishes, frogs and mammals, lineage-specific gene duplications were also detected in lizards. Furthermore, extensive gains and losses of T2R genes were detected in each lineage during their evolution, resulting in widely differing T2R gene repertoires.</p> <p>Conclusion</p> <p>These results further support the hypotheses that T2R gene repertoires are closely related to the dietary habits of different species and that birth-and-death evolution is associated with adaptations to dietary changes.</p

Diagenesis and reservoir quality of Neoproterozoic dolomitized microbialites following multi-stage diagenetic fluid activity: a case study of the Sinian Dengying Formation, China

Neoproterozoic marine microbialites have been targets for exploration and hydrocarbon reservoir development. The original depositional fabric and diagenesis control the pore systems of microbialites, leading to the complicated origin of microbialite reservoirs. This study aimed to reveal the origin of microbialite reservoirs following multi-stage diagenetic fluid activity in the fourth Member of the Dengying Formation in the central Sichuan Basin in southwestern China. The fourth Member of the Sinian Dengying Formation developed dolomitized microbialites, mainly including stromatolites, laminates, and thrombolites. Based on the background of tectonic movement, petrology and geochemistry examinations were executed to analyze the origin of the microbialite reservoir. Based on the cathodoluminescence and the homogenization temperature of the brine inclusions, it is credible that there were four stages of diagenetic fluid activities in the burial diagenesis. In the first stage, the microbialite reservoir was charged by oil in the Silurian period, with evidence from residual asphalt around the pores. In the second stage, dolomite precipitated to incompletely fill the pore spaces. In the third stage, the silica-rich diagenetic fluid with high temperature resulted in the precipitation of authigenic quartz. In the last stage, the oil charged again during the Triassic period, followed by siliceous filling, with residual asphalt filling the pore spaces. There were two stages of subaerial emergence, which occurred in two episodes of the Sinian-Early Cambrian Tongwan movement. The evidence for the two tectonic events includes two phases of dolomites with meteoric water origin, two cycles of V, Sr, and Na element profiles, two instances of negative excursion δ18O isotope, and two cavity layers. By comparison, the karstification of reservoirs in the Tongwan III episode could generate a higher quality of reservoir than that in the Tongwan II episode. As a result, the quality of the microbialite reservoir from the fourth Member of the Dengying Formation was mainly improved by the subaerial exposure in the Tongwan III episode and then was partly destroyed by the siliceous filling. The identification of multi-staged diagenetic fluid charging can illustrate the evolution of the reservoir quality of Neoproterozoic microbialites

Increased fibroblast functionality on CNN2-loaded titania nanotubes

Infection and epithelial downgrowth are major problems associated with maxillofacial percutaneous implants. These complications are mainly due to the improper closure of the implant–skin interface. Therefore, designing a percutaneous implant that better promotes the formation of a stable soft tissue biologic seal around percutaneous sites is highly desirable. Additionally, the fibroblast has been proven to play an important role in the formation of biologic seals. In this study, titania nanotubes were filled with 11.2 kDa C-terminal CCN2 (connective tissue growth factor) fragment, which could exert full CCN2 activity to increase the biological functionality of fibroblasts. This drug delivery system was fabricated on a titanium implant surface. CCN2 was loaded into anodized titania nanotubes using a simplified lyophilization method and the loading efficiency was approximately 80%. Then, the release kinetics of CCN2 from these nanotubes was investigated. Furthermore, the influence of CCN2-loaded titania nanotubes on fibroblast functionality was examined. The results revealed increased fibroblast adhesion at 0.25, 0.5, 1, 2, 4, and 24 hours, increased fibroblast viability over the course of 5 days, as well as enhanced actin cytoskeleton organization on CCN2-loaded titania nanotubes surfaces compared to uncoated, unmodified counterparts. Therefore, the results from this in vitro study demonstrate that CCN2-loaded titania nanotubes have the ability to increase fibroblast functionality and should be further studied as a method of promoting the formation of a stable soft tissue biologic seal around percutaneous sites

Research Progress on the Metabolites Formation Mechanism of Plant Jiaosu

Plant Jiaosu is a kind of product made from fruit and vegetable cereals as the main raw material by microbial fermentation. It has been gradually favored by the public because of its non-toxic and harmless characteristics and multiple physiological functions. Understanding the metabolic mechanisms of plant Jiaosu plays an important role in improving their quality. However, there are still few summaries on the metabolic mechanism of plant Jiaosu. This paper comprehensively analyzes the research progress of plant Jiaosu, and introduces the related metabolic pathways, product change analysis, product formation influencing factors, flavor source and flavor substance changes of plant Jiaosu in the process of plant ferment glycolysis. The future development of plant Jiaosu is discussed, which provides a reference for the further research and development of plant Jiaosu

[18F]AlF-NOTA-ADH-1: A new PET molecular radiotracer for imaging of N-cadherin-positive tumors

BackgroundThe cell adhesion molecule (CAM) N-cadherin has become an important target for tumor therapy. The N-cadherin antagonist, ADH-1, exerts significant antitumor activity against N-cadherin-expressing cancers.MethodsIn this study, [18F]AlF-NOTA-ADH-1 was radiosynthesized. An in vitro cell binding test was performed, and the biodistribution and micro-PET imaging of the probe targeting N-cadherin were also studied in vivo.ResultsRadiolabeling of ADH-1 with [18F]AlF achieved a yield of up to 30% (not decay-corrected) with a radiochemical purity of &gt;97%. The cell uptake study showed that Cy3-ADH-1 binds to SW480 cells but weakly binds to BXPC3 cells in the same concentration range. The biodistribution results demonstrated that [18F]AlF-NOTA-ADH-1 had a good tumor/muscle ratio (8.70±2.68) in patient-derived xenograft (PDX) tumor xenografts but a lower tumor/muscle ratio (1.91±0.69) in SW480 tumor xenografts and lowest tumor/muscle ratio (0.96±0.32) in BXPC3 tumor xenografts at 1 h post-injection (p.i.) These findings were in accordance with the immunohistochemistry results. The micro PET imaging results revealed good [18F]AlF-NOTA-ADH-1 tumor uptake in pancreatic cancer PDX xenografts with strong positive N-calcium expression, while lower tumor uptake in SW480 xenografts with positive expression of N-cadherin, and significantly lower tumor uptake in BXPC3 xenografts with low expression of N-cadherin, which was consistent with the biodistribution and immunohistochemistry results. The N-cadherin-specific binding of [18F]AlF-NOTA-ADH-1 was further verified by a blocking experiment involving coinjection of a non radiolabeled ADH-1 peptide, resulting in a significant reduction in tumor uptake in PDX xenografts and SW480 tumor.Conclusion[18F]AlF-NOTA-ADH-1 was successfully radiosynthesized, and Cy3-ADH-1 showed favorable N-cadherin-specific targeting ability by in vitro data. The biodistribution and microPET imaging of the probe further showed that [18F]AlF-NOTA-ADH-1 could discern different expressions of N-cadherin in tumors. Collectively, the findings demonstrated the potential of [18F]AlF-NOTA-ADH-1 as a PET imaging probe for non-invasive evaluation of the N-cadherin expression in tumors

Evolution of Olfactory Receptor Genes in Primates Dominated by Birth-and-Death Process

Olfactory receptor (OR) is a large family of G protein–coupled receptors that can detect odorant in order to generate the sense of smell. They constitute one of the largest multiple gene families in animals including primates. To better understand the variation in odor perception and evolution of OR genes among primates, we computationally identified OR gene repertoires in orangutans, marmosets, and mouse lemurs and investigated the birth-and-death process of OR genes in the primate lineage. The results showed that 1) all the primate species studied have no more than 400 intact OR genes, fewer than rodents and canine; 2) Despite the similar number of OR genes in the genome, the makeup of the OR gene repertoires between different primate species is quite different as they had undergone dramatic birth-and-death evolution with extensive gene losses in the lineages leading to current species; 3) Apes and Old World monkey (OWM) have similar fraction of pseudogenes, whereas New World monkey (NWM) have fewer pseudogenes. To measure the selective pressure that had affected the OR gene repertoires in primates, we compared the ratio of nonsynonymous with synonymous substitution rates by using 70 one-to-one orthologous quintets among five primate species. We found that OR genes showed relaxed selective constraints in apes (humans, chimpanzees, and orangutans) than in OWMs (macaques) and NWMs (marmosets). We concluded that OR gene repertoires in primates have evolved in such a way to adapt to their respective living environments. Differential selective constraints might play important role in the primate OR gene evolution in each primate species

Genomic and Genetic Evidence for the Loss of Umami Taste in Bats

Umami taste is responsible for sensing monosodium glutamate, nucleotide enhancers, and other amino acids that are appetitive to vertebrates and is one of the five basic tastes that also include sour, salty, sweet, and bitter. To study how ecological factors, especially diets, impact the evolution of the umami taste, we examined the umami taste receptor gene Tas1r1 in a phylogenetically diverse group of bats including fruit eaters, insect eaters, and blood feeders. We found that Tas1r1 is absent, unamplifiable, or pseudogenized in each of the 31 species examined, including the genome sequences of two species, suggesting the loss of the umami taste in most, if not all, bats regardless of their food preferences. Most strikingly, vampire bats have also lost the sweet taste receptor gene Tas1r2 and the gene required for both umami and sweet tastes (Tas1r3), being the first known mammalian group to lack two of the five tastes. The puzzling absence of the umami taste in bats calls for a better understanding of the roles that this taste plays in the daily life of vertebrates

Fractional-Order Control Method Based on Twin-Delayed Deep Deterministic Policy Gradient Algorithm

In this paper, a fractional-order control method based on the twin-delayed deep deterministic policy gradient (TD3) algorithm in reinforcement learning is proposed. A fractional-order disturbance observer is designed to estimate the disturbances, and the radial basis function network is selected to approximate system uncertainties in the system. Then, a fractional-order sliding-mode controller is constructed to control the system, and the parameters of the controller are tuned using the TD3 algorithm, which can optimize the control effect. The results show that the fractional-order control method based on the TD3 algorithm can not only improve the closed-loop system performance under different operating conditions but also enhance the signal tracking capability