Positive selection for the male functionality of a co-retroposed gene in the hominoids

<p>Abstract</p> <p>Background</p> <p>New genes generated by retroposition are widespread in humans and other mammalian species. Usually, this process copies a single parental gene and inserts it into a distant genomic location. However, retroposition of two adjacent parental genes, <it>i.e</it>. co-retroposition, had not been reported until the hominoid chimeric gene, <it>PIPSL</it>, was identified recently. It was shown how two genes linked in tandem (phosphatidylinositol-4-phosphate 5-kinase, type I, alpha, <it>PIP5K1A </it>and proteasome 26S subunit, non-ATPase, 4, <it>PSMD4</it>) could be co-retroposed from a single RNA molecule to form this novel chimeric gene. However, understanding of the origination and biological function of <it>PIPSL </it>requires determination of the coding potential of this gene as well as the evolutionary forces acting on its hominoid copies.</p> <p>Results</p> <p>We tackled these problems by analyzing the evolutionary signature in both within-species variation and between species divergence in the sequence and structure of the gene. We revealed a significant evolutionary signature: the coding region has significantly lower sequence variation, especially insertions and deletions, suggesting that the human copy may encode a protein. Moreover, a survey across five different hominoid species revealed that all adaptive changes of <it>PSMD4</it>-derived regions occurred on branches leading to human and chimp rather than other hominoid lineages. Finally, computational analysis suggests testis-specific transcription of <it>PIPSL </it>is regulated by tissue-dependent methylation rather than some transcriptional leakage.</p> <p>Conclusion</p> <p>Therefore, this set of analyses showed that <it>PIPSL </it>is an extraordinary co-retroposed protein-coding gene that may participate in the male functions of humans and its close relatives.</p

ABrowse - a customizable next-generation genome browser framework

<p>Abstract</p> <p>Background</p> <p>With the rapid growth of genome sequencing projects, genome browser is becoming indispensable, not only as a visualization system but also as an interactive platform to support open data access and collaborative work. Thus a customizable genome browser framework with rich functions and flexible configuration is needed to facilitate various genome research projects.</p> <p>Results</p> <p>Based on next-generation web technologies, we have developed a general-purpose genome browser framework ABrowse which provides interactive browsing experience, open data access and collaborative work support. By supporting Google-map-like smooth navigation, ABrowse offers end users highly interactive browsing experience. To facilitate further data analysis, multiple data access approaches are supported for external platforms to retrieve data from ABrowse. To promote collaborative work, an online user-space is provided for end users to create, store and share comments, annotations and landmarks. For data providers, ABrowse is highly customizable and configurable. The framework provides a set of utilities to import annotation data conveniently. To build ABrowse on existing annotation databases, data providers could specify SQL statements according to database schema. And customized pages for detailed information display of annotation entries could be easily plugged in. For developers, new drawing strategies could be integrated into ABrowse for new types of annotation data. In addition, standard web service is provided for data retrieval remotely, providing underlying machine-oriented programming interface for open data access.</p> <p>Conclusions</p> <p>ABrowse framework is valuable for end users, data providers and developers by providing rich user functions and flexible customization approaches. The source code is published under GNU Lesser General Public License v3.0 and is accessible at <url>http://www.abrowse.org/</url>. To demonstrate all the features of ABrowse, a live demo for <it>Arabidopsis thaliana </it>genome has been built at <url>http://arabidopsis.cbi.edu.cn/</url>.</p

Analysis of Conveyance Losses from Tertiary Irrigation Network

Irrigation canals are generally made through porous soil formations, since the soil is loose porous media – a huge amount of canal water is lost to conveyance losses. The situation becomes direr when these losses result in non-beneficial losses. The Sindh province of Pakistan has more than 70% saline groundwater, conveyance losses to such areas in the province not only become unusable but also creates water management problems. Perhaps the only cost-effective way to address these losses is canal lining. The present study was conducted in the command area of Belharo distributary, Sindh, Pakistan with an aim to determine the extent of losses from the tertiary irrigated network as these water channels are less considered in the literature with regards of conveyance losses. Using water balance method, conveyance efficiency and conveyance losses at 30% lined and 50 and 75% unlined length of the watercourses was observed. The results revealed that the tertiary irrigation channels face an average of 43% conveyance losses and major proportion of these losses is lost to non-beneficial losses from the study area. The study further suggests 75% lining of watercourses in order to minimize non-beneficial losses. This study also infers that with the use of geo-membrane lining, sizeable amount of fresh water can be saved. Doi: 10.28991/cej-2021-03091756 Full Text: PD

An analytical model for shear behaviour of bolted rock joints

Rock bolts have been widely used to reinforce the jointed rock mass. Modelling the mechanical shear behaviors of the bolted rock joints are difficult due to the complex interactions between bolts and rock joints. The applied pretension forces combined with the axial loads developed in the bolt act as the normal forces which are applied to the rock joints. However, these combined normal forces are not considered in the existing analytical models. An analytical model is proposed in this study to predict the shear behavior of the bolted rock joints, by taking into account the pretension forces, the axial forces developed in the bolt, the interfacial bond stress between the bolt and grout, and dowel shear loads acting transversely to the bolt axis. The proposed analytical model is able to provide complete curves of the dowel shear loads, axial loads, and the global shear loads as a function of the joint shear displacement. The analytically predicted axial load vs shear displacement curves and the global shear load vs shear displacement curves are verified by available experimental tests. The validation shows that the proposed model has the capacity to predict the global shear load evolution as well as the axial load evolution. The factors such as the pretension forces, the bolt inclination angles, the concrete strength and the rock joint friction are successfully accounted for in the analytical model

Metastasis-on-a-chip mimicking the progression of kidney cancer in the liver for predicting treatment efficacy.

Metastasis is one of the most important factors that lead to poor prognosis in cancer patients, and effective suppression of the growth of primary cancer cells in a metastatic site is paramount in averting cancer progression. However, there is a lack of biomimetic three-dimensional (3D) in vitro models that can closely mimic the continuous growth of metastatic cancer cells in an organ-specific extracellular microenvironment (ECM) for assessing effective therapeutic strategies. Methods: In this metastatic tumor progression model, kidney cancer cells (Caki-1) and hepatocytes (i.e., HepLL cells) were co-cultured at an increasing ratio from 1:9 to 9:1 in a decellularized liver matrix (DLM)/gelatin methacryloyl (GelMA)-based biomimetic liver microtissue in a microfluidic device. Results:Via this model, we successfully demonstrated a linear anti-cancer relationship between the concentration of anti-cancer drug 5-Fluorouracil (5-FU) and the percentage of Caki-1 cells in the co-culture system (R2 = 0.89). Furthermore, the Poly(lactide-co-glycolide) (PLGA)-poly(ethylene glycol) (PEG)-based delivery system showed superior efficacy to free 5-FU in killing Caki-1 cells. Conclusions: In this study, we present a novel 3D metastasis-on-a-chip model mimicking the progression of kidney cancer cells metastasized to the liver for predicting treatment efficacy. Taken together, our study proved that the tumor progression model based on metastasis-on-a-chip with organ-specific ECM would provide a valuable tool for rapidly assessing treatment regimens and developing new chemotherapeutic agents

Viral Infection Induces Expression of Novel Phased MicroRNAs from Conserved Cellular MicroRNA Precursors

RNA silencing, mediated by small RNAs including microRNAs (miRNAs) and small interfering RNAs (siRNAs), is a potent antiviral or antibacterial mechanism, besides regulating normal cellular gene expression critical for development and physiology. To gain insights into host small RNA metabolism under infections by different viruses, we used Solexa/Illumina deep sequencing to characterize the small RNA profiles of rice plants infected by two distinct viruses, Rice dwarf virus (RDV, dsRNA virus) and Rice stripe virus (RSV, a negative sense and ambisense RNA virus), respectively, as compared with those from non-infected plants. Our analyses showed that RSV infection enhanced the accumulation of some rice miRNA*s, but not their corresponding miRNAs, as well as accumulation of phased siRNAs from a particular precursor. Furthermore, RSV infection also induced the expression of novel miRNAs in a phased pattern from several conserved miRNA precursors. In comparison, no such changes in host small RNA expression was observed in RDV-infected rice plants. Significantly RSV infection elevated the expression levels of selective OsDCLs and OsAGOs, whereas RDV infection only affected the expression of certain OsRDRs. Our results provide a comparative analysis, via deep sequencing, of changes in the small RNA profiles and in the genes of RNA silencing machinery induced by different viruses in a natural and economically important crop host plant. They uncover new mechanisms and complexity of virus-host interactions that may have important implications for further studies on the evolution of cellular small RNA biogenesis that impact pathogen infection, pathogenesis, as well as organismal development

The numerical analysis of the flow on the smooth and nonsmooth boundaries by IBEM/DBIEM

The value of the tangential velocity on the Boundary Value Problem (BVP) is inaccurate when comparing the results with analytical solutions by Indirect Boundary Element Method (IBEM), especially at the intersection region where the normal vector is changing rapidly (named nonsmooth boundary). In this study, the singularity of the BVP, which is directly arranged in the center of the surface of the fluid computing domain, is moved outside the computational domain by using the Desingularized Boundary Integral Equation Method (DBIEM). In order to analyze the accuracy of the IBEM/DBIEM and validate the above-mentioned problem, three-dimensional uniform flow over a sphere has been presented. The convergent study of the presented model has been investigated, including desingularized distance in the DBIEM. Then, the numerical results were compared with the analytical solution. It was found that the accuracy of velocity distribution in the flow field has been greatly improved at the intersection region, which has suddenly changed the boundary surface shape of the fluid domain. The conclusions can guide the study on the flow over nonsmooth boundaries by using boundary value method

Aortic dissection induced by vascular endothelial growth factor inhibitors

Vascular endothelial growth factor (VEGF) contributes to angiogenesis and vasculogenesis. The occurrence and progression of tumors are accompanied by angiogenesis. Vascular endothelial growth factor inhibitors (VEGFI) have been used in anti-tumor treatment. However, aortic dissection (AD) is one of the VEGFI-associated adverse reactions with cute onset, rapid progression, and high case fatality rate. We collected case reports of VEGFI related to aortic dissection in PubMed and CNKI (China National Knowledge Infrastructure) from inception to 28 April 2022. Seventeen case reports were selected. The medication included sunitinib, sorafenib, pazopanib, axitinib, apatinib, anlotinib, bevacizumab, and ramucirumab. This review discusses the pathology, risk factors, diagnosis, and treatment of AD. Vascular endothelial growth factor inhibitors are related to aortic dissection. Although current literature lacks clear statistical evidence on the population, we offer points to encourage further confirmation of the best methods of care for these patients

NF-κB activation is critical for bacterial lipoprotein tolerance-enhanced bactericidal activity in macrophages during microbial infection

Tolerance to bacterial components represents an essential regulatory mechanism during bacterial infection. Bacterial lipoprotein (BLP)-induced tolerance confers protection against microbial sepsis by attenuating inflammatory responses and augmenting antimicrobial activity in innate phagocytes. It has been well-documented that BLP tolerance-attenuated proinflammatory cytokine production is associated with suppressed TLR2 signalling pathway; however, the underlying mechanism(s) involved in BLP tolerance-enhanced antimicrobial activity is unclear. Here we report that BLP-tolerised macrophages exhibited accelerated phagosome maturation and enhanced bactericidal activity upon bacterial infection, with upregulated expression of membrane-trafficking regulators and lysosomal enzymes. Notably, bacterial challenge resulted in a strong activation of NF-κB pathway in BLP-tolerised macrophages. Importantly, activation of NF-κB pathway is critical for BLP tolerance-enhanced antimicrobial activity, as deactivation of NF-κB in BLP-tolerised macrophages impaired phagosome maturation and intracellular killing of the ingested bacteria. Finally, activation of NF-κB pathway in BLP-tolerised macrophages was dependent on NOD1 and NOD2 signalling, as knocking-down NOD1 and NOD2 substantially inhibited bacteria-induced activation of NF-κB and overexpression of Rab10 and Acp5, two membrane-trafficking regulators and lysosomal enzymes contributed to BLP tolerance-enhanced bactericidal activity. These results indicate that activation of NF-κB pathway is essential for BLP tolerance-augmented antimicrobial activity in innate phagocytes and depends primarily on both NOD1 and NOD2