The ancient function of RB-E2F Pathway: insights from its evolutionary history

<p>Abstract</p> <p>Background</p> <p>The RB-E2F pathway is conserved in most eukaryotic lineages, including animals and plants. E2F and RB family proteins perform crucial functions in cycle controlling, differentiation, development and apoptosis. However, there are two kinds of E2Fs (repressive E2Fs and active E2Fs) and three RB family members in human. Till now, the detail evolutionary history of these protein families and how RB-E2F pathway evolved in different organisms remain poorly explored.</p> <p>Results</p> <p>We performed a comprehensive evolutionary analysis of E2F, RB and DP (dimerization partners of E2Fs) protein family in representative eukaryotic organisms. Several interesting facts were revealed. First, orthologues of RB, E2F, and DP family are present in several representative unicellular organisms and all multicellular organisms we checked. Second, ancestral E2F, RB genes duplicated before placozoans and bilaterians diverged, thus E2F family was divided into E2F4/5 subgroup (including repressive E2Fs: E2F4 and E2F5) and E2F1/2/3 subgroup (including active E2Fs: E2F1, E2F2 and E2F3), RB family was divided into RB1 subgroup (including RB1) and RBL subgroup (including RBL1 and RBL2). Third, E2F4 and E2F5 share more sequence similarity with the predicted E2F ancestral sequence than E2F1, E2F2 and E2F3; E2F4 and E2F5 also possess lower evolutionary rates and higher purification selection pressures than E2F1, E2F2 and E2F3. Fourth, for RB family, the RBL subgroup proteins possess lower evolutionary rates and higher purification selection pressures compared with RB subgroup proteins in vertebrates,</p> <p>Conclusions</p> <p>Protein evolutionary rates and purification selection pressures are usually linked with protein functions. We speculated that function conducted by E2F4/5 subgroup and RBL subgroup proteins might mainly represent the ancient function of RB-E2F pathway, and the E2F1/2/3 subgroup proteins and RB1 protein might contribute more to functional diversification in RB-E2F pathway. Our results will enhance the current understanding of RB-E2F pathway and will also be useful to further functional studies in human and other model organisms.</p> <p>Reviewers</p> <p>This article was reviewed by Dr. Pierre Pontarotti, Dr. Arcady Mushegian and Dr. Zhenguo Lin (nominated by Dr. Neil Smalheiser).</p

Customers’ Mode Choice Behaviors of Express Service Based on Latent Class Analysis and Logit Model

As the parcel delivery service is booming in China, the competition among express companies intensifies. This paper employed multinomial logit model (MNL) and latent class model (LCM) to investigate customers’ express service choice behavior, using data from a SP survey. The attributes and attribute levels that matter most to express customers are identified. Meanwhile, the customers are divided into two segments (penny pincher segment and high-end segment) characterized by their taste heterogeneity. The results indicate that the LCM performs statistically better than MNL in our sample. Therefore, more attention should be paid to the taste heterogeneity, especially for further academic and policy research in freight choice behavior

Heat stress exposure cause alterations in intestinal microbiota, transcriptome, and metabolome of broilers

IntroductionHeat stress can affect the production of poultry through complex interactions between genes, metabolites and microorganisms. At present, it is unclear how heat stress affects genetic, metabolic and microbial changes in poultry, as well as the complex interactions between them.MethodsThus, at 28  days of age a total of 200 Arbor Acres broilers with similar body weights were randomly divided into the control (CON) and heat stress treatment (HS). There were 5 replicates in CON and HS, respectively, 20 per replication. From the 28–42  days, the HS was kept at 31 ± 1°C (9:00–17:00, 8 h) and other time was maintained at 21 ± 1°C as in the CON. At the 42nd day experiment, we calculated the growth performance (n = 8) of broilers and collected 3 and 6 cecal tissues for transcriptomic and metabolomic investigation and 4 cecal contents for metagenomic investigation of each treatment.Results and discussionThe results indicate that heat stress significantly reduced the average daily gain and body weight of broilers (value of p &lt; 0.05). Transcriptome KEGG enrichment showed that the differential genes were mainly enriched in the NF-kB signaling pathway. Metabolomics results showed that KEGG enrichment showed that the differential metabolites were mainly enriched in the mTOR signaling pathway. 16S rDNA amplicon sequencing results indicated that heat stress increased the relative abundance of Proteobacteria decreased the relative abundance of Firmicutes. Multi-omics analysis showed that the co-participating pathway of differential genes, metabolites and microorganisms KEGG enrichment was purine metabolism. Pearson correlation analysis found that ornithine was positively correlated with SULT1C3, GSTT1L and g_Lactobacillus, and negatively correlated with CALB1. PE was negatively correlated with CALB1 and CHAC1, and positively with g_Alistipes. In conclusion, heat stress can generate large amounts of reactive oxygen and increase the types of harmful bacteria, reduce intestinal nutrient absorption and antioxidant capacity, and thereby damage intestinal health and immune function, and reduce growth performance indicators. This biological process is manifested in the complex regulation, providing a foundational theoretical basis for solving the problem of heat stress

A survey of parametric modelling methods for designing the head of a high-speed train

With the continuous increase of the running speed, the head shape of the high-speed train (HST) turns out to be a critical factor for further speed boost. In order to cut down the time used in the HST head design and improve the modelling efficiency, various parametric modelling methods have been widely applied in the optimization design of the HST head to obtain an optimal head shape so that the aerodynamic effect acting on the head of HSTs can be reduced and more energy can be saved. This paper reviews these parametric modelling methods and classifies them into four categories: 2D, 3D, CATIA-based, and mesh deformation-based parametric modelling methods. Each of the methods is introduced, and the advantages and disadvantages of these methods are identified. The simulation results are presented to demonstrate that the aerodynamic performance of the optimal models constructed by these parametric modelling methods has been improved when compared with numerical calculation results of the original models or the prototype models of running trains. Since different parametric modelling methods used different original models and optimization methods, few publications could be found which compare the simulation results of the aerodynamic performance among different parametric modelling methods. In spite of this, these parametric modelling methods indicate more local shape details will lead to more accurate simulation results, and fewer design variables will result in higher computational efficiency. Therefore, the ability of describing more local shape details with fewer design variables could serve as a main specification to assess the performance of various parametric modelling methods. The future research directions may concentrate on how to improve such ability

On-water surface synthesis of charged two-dimensional polymer single crystals via the irreversible Katritzky reaction

Two-dimensional polymers (2DPs) and their layer-stacked 2D covalent organic frameworks (2D COFs) are classes of structurally defined crystalline polymeric materials with exotic physical and chemical properties. Yet, synthesizing 2DP and 2D COF single crystals via irreversible reactions remains challenging. Here we report the synthesis of charged 2DP (C2DP) single crystals through an irreversible Katritzky reaction, under pH control, on a water surface. The periodically ordered 2DPs comprise aromatic pyridinium cations and counter BF4− anions. The C2DP crystals, which are composed of linked porphyrin and pyrylium monomers (C2DP-Por), have a tunable thickness of 2–30 nm and a lateral domain size up to 120 μm2. Single crystals with a square lattice (a = b = 30.5 Å) are resolved by imaging and diffraction methods with near-atomic precision. Furthermore, the integration of C2DP-Por crystals in an osmotic power generator device shows an excellent chloride ion selectivity with a coefficient value reaching ~0.9 and an output power density of 4 W m−2, superior to those of graphene and boron nitride

A genome-wide association study of coat color in Chinese Rex rabbits

Coat color is an important phenotypic characteristic of the domestic rabbit (Oryctolagus cuniculus) and has specific economic importance in the Rex rabbit industry. Coat color varies considerably among different populations of rabbits, and several causal genes for this variation have been thoroughly studied. Nevertheless, the candidate genes affecting coat color variation in Chinese Rex rabbits remained to be investigated. In this study, we collected blood samples from 250 Chinese Rex rabbits with six different coat colors. We performed genome sequencing using a restriction site-associated DNA sequencing approach. A total of 91,546 single nucleotide polymorphisms (SNPs), evenly distributed among 21 autosomes, were identified. Genome-wide association studies (GWAS) were performed using a mixed linear model, in which the individual polygenic effect was fitted as a random effect. We detected a total of 24 significant SNPs that were located within a genomic region on chromosome 4 (OCU4). After re-fitting the most significant SNP (OCU4:13,434,448, p = 1.31e-12) as a covariate, another near-significant SNP (OCU4:11,344,946, p = 7.03e-07) was still present. Hence, we conclude that the 2.1-Mb genomic region located between these two significant SNPs is significantly associated with coat color in Chinese Rex rabbits. The well-studied coat-color-associated agouti signaling protein (ASIP) gene is located within this region. Furthermore, low genetic differentiation was also observed among the six coat color varieties. In conclusion, our results confirmed that ASIP is a putative causal gene affecting coat color variation in Chinese Rex rabbits

Induction of autophagy is a key component of all-trans-retinoic acid-induced differentiation in leukemia cells and a potential target for pharmacological modulation

Acute myeloid leukemia (AML) is characterized by the accumulation of immature blood cell precursors in the bone marrow. Pharmacologically overcoming the differentiation block in this condition is an attractive therapeutic avenue, which has achieved success only in a subtype of AML, acute promyelocytic leukemia (APL). Attempts to emulate this success in other AML subtypes have thus far been unsuccessful. Autophagy is a conserved protein degradation pathway with important roles in mammalian cell differentiation, particularly within the hematopoietic system. In the study described here, we investigated the functional importance of autophagy in APL cell differentiation. We found that autophagy is increased during all-trans-retinoic acid (ATRA)-induced granulocytic differentiation of the APL cell line NB4 and that this is associated with increased expression of LC3II and GATE-16 proteins involved in autophagosome formation. Autophagy inhibition, using either drugs (chloroquine/3-methyladenine) or short-hairpin RNA targeting the essential autophagy gene ATG7, attenuates myeloid differentiation. Importantly, we found that enhancing autophagy promotes ATRA-induced granulocytic differentiation of an ATRA-resistant derivative of the non-APL AML HL60 cell line (HL60-Diff-R). These data support the development of strategies to stimulate autophagy as a novel approach to promote differentiation in AML