A comparative genome analysis of gene expression reveals different regulatory mechanisms between mouse and human embryo pre-implantation development

<p>Abstract</p> <p>Background</p> <p>Pre-implantation development is a crucial step in successful implantation and pregnancy in mammals. It has been studied in depth, but mostly in laboratory animal models. Less is known about the regulatory mechanism involved in the pre-implantation development in humans and about the comparative aspects.</p> <p>Methods</p> <p>Here, we employed the microarray datasets from the public database library of GEO and applied comparative analysis of genome wide temporal gene expression data based on statistical analysis and functional annotation for both mouse and human, demonstrating the discordance between the regulatory mechanisms of both mouse and human pre-implantation development.</p> <p>Results</p> <p>There were differences between mouse and human pre-implantation development both in the global gene expression pattern and in the expression changes of individual genes at each stage, including different major transient waves of transcription profiles and some stage-specific genes and significantly related pathways. There also appeared to be different functional changes from one stage to another between mouse and human.</p> <p>Conclusions</p> <p>The analysis presented here lead to interesting and complementary conclusions that the regulatory mechanism of human pre-implantation development is not completely the same as the mouse. Not as the fact that 1-cell to 2-cell stage is important for mouse pre-implantation development, the 4-cell stage and 8-cell stage are both essential for human. Unlike in mouse, of which most of pathways found were related to energy, RNA and protein metabolism, the identified pathways in human were mostly disease-related and associated with human pre-implantation embryonic development. All of these suggest that a further comparative analysis should be required for applying the result of mouse expression data to human research or therapy, particularly in pre-implantation developments. Our study provides several potential targets of genes and pathways for studying the regulatory mechanism of human pre-implantation development using mouse model.</p

FoxO gene family evolution in vertebrates

<p>Abstract</p> <p>Background</p> <p>Forkhead box, class O (FoxO) belongs to the large family of forkhead transcription factors that are characterized by a conserved forkhead box DNA-binding domain. To date, the FoxO group has four mammalian members: FoxO1, FoxO3a, FoxO4 and FoxO6, which are orthologs of DAF16, an insulin-responsive transcription factor involved in regulating longevity of worms and flies. The degree of homology between these four members is high, especially in the forkhead domain, which contains the DNA-binding interface. Yet, mouse FoxO knockouts have revealed that each FoxO gene has its unique role in the physiological process. Whether the functional divergences are primarily due to adaptive selection pressure or relaxed selective constraint remains an open question. As such, this study aims to address the evolutionary mode of FoxO, which may lead to the functional divergence.</p> <p>Results</p> <p>Sequence similarity searches have performed in genome and scaffold data to identify homologues of FoxO in vertebrates. Phylogenetic analysis was used to characterize the family evolutionary history by identifying two duplications early in vertebrate evolution. To determine the mode of evolution in vertebrates, we performed a rigorous statistical analysis with FoxO gene sequences, including relative rate ratio tests, branch-specific <it>d</it>_<it>N</it>/<it>d</it>_{<it>S </it>}ratio tests, site-specific <it>d</it>_<it>N</it>/<it>d</it>_{<it>S </it>}ratio tests, branch-site <it>d</it>_<it>N</it>/<it>d</it>_{<it>S </it>}ratio tests and clade level amino acid conservation/variation patterns analysis. Our results suggest that FoxO is constrained by strong purifying selection except four sites in FoxO6, which have undergone positive Darwinian selection. The functional divergence in this family is best explained by either relaxed purifying selection or positive selection.</p> <p>Conclusion</p> <p>We present a phylogeny describing the evolutionary history of the FoxO gene family and show that the genes have evolved through duplications followed by purifying selection except for four sites in FoxO6 fixed by positive selection lie mostly within the non-conserved optimal PKB motif in the C-terminal part. Relaxed selection may play important roles in the process of functional differentiation evolved through gene duplications as well.</p

基于CIM技术的智慧交通项目管理建设方案研究

This paper takes smart transportation as the research object, selects the construction of project management as the research problem, and proposes to use CIM as the supporting technology. From the perspective of various digital fusion technologies, it emphasizes the information reliability of multi-dimensional model calculation, which is used to guide the management of urban transportation hub projects

Correlated Mutation Analysis on the Catalytic Domains of Serine/Threonine Protein Kinases

BACKGROUND:Protein kinases (PKs) have emerged as the largest family of signaling proteins in eukaryotic cells and are involved in every aspect of cellular regulation. Great progresses have been made in understanding the mechanisms of PKs phosphorylating their substrates, but the detailed mechanisms, by which PKs ensure their substrate specificity with their structurally conserved catalytic domains, still have not been adequately understood. Correlated mutation analysis based on large sets of diverse sequence data may provide new insights into this question. METHODOLOGY/PRINCIPAL FINDINGS:Statistical coupling, residue correlation and mutual information analyses along with clustering were applied to analyze the structure-based multiple sequence alignment of the catalytic domains of the Ser/Thr PK family. Two clusters of highly coupled sites were identified. Mapping these positions onto the 3D structure of PK catalytic domain showed that these two groups of positions form two physically close networks. We named these two networks as theta-shaped and gamma-shaped networks, respectively. CONCLUSIONS/SIGNIFICANCE:The theta-shaped network links the active site cleft and the substrate binding regions, and might participate in PKs recognizing and interacting with their substrates. The gamma-shaped network is mainly situated in one side of substrate binding regions, linking the activation loop and the substrate binding regions. It might play a role in supporting the activation loop and substrate binding regions before catalysis, and participate in product releasing after phosphoryl transfer. Our results exhibit significant correlations with experimental observations, and can be used as a guide to further experimental and theoretical studies on the mechanisms of PKs interacting with their substrates

A proteomic analysis of the chromoplasts isolated from sweet orange fruits [Citrus sinensis (L.) Osbeck]

Here, a comprehensive proteomic analysis of the chromoplasts purified from sweet orange using Nycodenz density gradient centrifugation is reported. A GeLC-MS/MS shotgun approach was used to identify the proteins of pooled chromoplast samples. A total of 493 proteins were identified from purified chromoplasts, of which 418 are putative plastid proteins based on in silico sequence homology and functional analyses. Based on the predicted functions of these identified plastid proteins, a large proportion (∼60%) of the chromoplast proteome of sweet orange is constituted by proteins involved in carbohydrate metabolism, amino acid/protein synthesis, and secondary metabolism. Of note, HDS (hydroxymethylbutenyl 4-diphosphate synthase), PAP (plastid-lipid-associated protein), and psHSPs (plastid small heat shock proteins) involved in the synthesis or storage of carotenoid and stress response are among the most abundant proteins identified. A comparison of chromoplast proteomes between sweet orange and tomato suggested a high level of conservation in a broad range of metabolic pathways. However, the citrus chromoplast was characterized by more extensive carotenoid synthesis, extensive amino acid synthesis without nitrogen assimilation, and evidence for lipid metabolism concerning jasmonic acid synthesis. In conclusion, this study provides an insight into the major metabolic pathways as well as some unique characteristics of the sweet orange chromoplasts at the whole proteome level

Regression-based approach for testing the association between multi-region haplotype configuration and complex trait

<p>Abstract</p> <p>Background</p> <p>It is quite common that the genetic architecture of complex traits involves many genes and their interactions. Therefore, dealing with multiple unlinked genomic regions simultaneously is desirable.</p> <p>Results</p> <p>In this paper we develop a regression-based approach to assess the interactions of haplotypes that belong to different unlinked regions, and we use score statistics to test the null hypothesis of non-genetic association. Additionally, multiple marker combinations at each unlinked region are considered. The multiple tests are settled via the <it>minP </it>approach. The <it>P </it>value of the "best" multi-region multi-marker configuration is corrected via Monte-Carlo simulations. Through simulation studies, we assess the performance of the proposed approach and demonstrate its validity and power in testing for haplotype interaction association.</p> <p>Conclusion</p> <p>Our simulations showed that, for binary trait without covariates, our proposed methods prove to be equal and even more powerful than htr and hapcc which are part of the FAMHAP program. Additionally, our model can be applied to a wider variety of traits and allow adjustment for other covariates. To test the validity, our methods are applied to analyze the association between four unlinked candidate genes and pig meat quality.</p

Continuous and Noninvasive Measurement of Arterial Pulse Pressure and Pressure Waveform using an Image-free Ultrasound System

The local beat-to-beat local pulse pressure (PP) and blood pressure waveform of arteries, especially central arteries, are important indicators of the course of cardiovascular diseases (CVDs). Nevertheless, noninvasive measurement of them remains a challenge in the clinic. This work presents a three-element image-free ultrasound system with a low-computational method for real-time measurement of local pulse wave velocity (PWV) and diameter waveforms, enabling real-time and noninvasive continuous PP and blood pressure waveforms measurement without calibration. The developed system has been well-validated in vitro and in vivo. In in vitro cardiovascular phantom experiments, the results demonstrated high accuracy in the measurement of PP (error < 3 mmHg) and blood pressure waveform (root-mean-square-errors (RMSE) < 2 mmHg, correlation coefficient (r) > textgreater 0.99). In subsequent human carotid experiments, the system was compared with an arterial tonometer, which showed excellent PP accuracy (mean absolute error (MAE) = 3.7 +- 3.4 mmHg) and pressure waveform similarity (RMSE = 3.7 +- 1.6 mmHg, r = 0.98 +- 0.01). Furthermore, comparative experiments with the volume clamp device demonstrated the system's ability to accurately trace blood pressure changes (induced by deep breathing) over a period of one minute, with the MAE of DBP, MAP, and SBP within 5 +- 8 mmHg. The present results demonstrate the accuracy and reliability of the developed system for continuous and noninvasive measurement of arterial PP and blood pressure waveform measurements, with potential applications in the diagnosis and prevention of CVDs.Comment: 13 pages, 12 figure

Engineered neutrophil-derived exosome-like vesicles for targeted cancer therapy

Neutrophils are the most abundant innate immune cells in human circulation; however, their derived exosomes have been rarely studied for tumor treatment. Here, we reported that exosomes from neutrophils (N-Ex) induce tumor cell apoptosis by delivering cytotoxic proteins and activating caspase signaling pathway. In addition, we decorated N-Ex with superparamagnetic iron oxide nanoparticles ( SPIONs) to achieve higher tumor-targeting therapeutic effect. We further fabricated exosome-like nanovesicles from neutrophils (NNVs) at high yield. Compared with liposome-loaded doxorubicin (DOX) and natural NNVs, DOX-loaded NNVs show an improved inhibition of tumor cell proliferation. Moreover, DOX-loaded, SPION-decorated NNVs selectively accumulate at the tumor sites under an external magnetic field, effectively restraining tumor growth and extensively prolonging the survival rate in mice. Overall, a simple and effective method to engineer N-Ex and NNVs at clinical applicable scale was developed, which enables the efficient and safe drug delivery for targeted and combined tumor therapy.Peer reviewe

Iridescent Daytime Radiative Cooling with No Absorption Peaks in the Visible Range

Coatings for passive radiative cooling applications must be highly reflected in the solar spectrum, and thus can hardly support any coloration without losing their functionality. In this work, a colorful daytime radiative cooling surface based on structural coloration is reported. A designed radiative cooler with a bioinspired array of truncated SiO2 microcones is manufactured via a self-assembly method and reactive ion etching. Complemented with a silver reflector, the radiative cooler exhibits broadband iridescent coloration due to the scattering induced by the truncated microcone array while maintaining an average reflectance of 95% in the solar spectrum and a high thermal emissivity (ε) of 0.95, owing to the reduced impedance mismatch provided by the patterned surface at infrared wavelengths, reaching an estimated cooling power of ≈143&nbsp;W&nbsp;m-2 at an ambient temperature of 25&nbsp;°C and a measured average temperature drop of 7.1&nbsp;°C under direct sunlight. This strong cooling performance is attributed to its bioinspired surface pattern, which promotes both the aesthetics and cooling capacity of the daytime radiative cooler