Subtype-specific collaborative transcription factor networks are promoted by OCT4 in the progression of prostate cancer

Interactive networks of transcription factors (TFs) have critical roles in epigenetic and gene regulation for cancer progression. It is required to clarify underlying mechanisms for transcriptional activation through concerted efforts of TFs. Here, we show the essential role of disease phase-specific TF collaboration changes in advanced prostate cancer (PC). Investigation of the transcriptome in castration-resistant PC (CRPC) revealed OCT4 as a key TF in the disease pathology. OCT4 confers epigenetic changes by promoting complex formation with FOXA1 and androgen receptor (AR), the central signals for the progression to CRPC. Meanwhile, OCT4 facilitates a distinctive complex formation with nuclear respiratory factor 1 (NRF1) to gain chemo-resistance in the absence of AR. Mechanistically, we reveal that OCT4 increases large droplet formations with AR/FOXA1 as well as NRF1 in vitro. Disruption of TF collaborations using a nucleoside analogue, ribavirin, inhibited treatment-resistant PC tumor growth. Thus, our findings highlight the formation of TF collaborations as a potent therapeutic target in advanced cancer.

Internet of Vehicles and Connected Smart Vehicles Communication System Towards Autonomous Driving

Internet of Vehicles (IoV) is one of the attractive solutions that revolutionized automotive services. IoV is the key concept toward smart and autonomous cars. Providing different wireless connectivity’s for vehicles permits the communication inside and outside the vehicle. These connectivities allow the vehicle to interact with other vehicles and with its environment. Autonomous driving is an innovative automotive service that will be enabled by the technology advancement related to IoV and connected cars. Big data technology has a significant impact on the development of autonomous driving and IOV concept as it refers to a huge interactive networks of information. In this paper, we focus on wireless technologies and the communication system to provide Vehicle-to-Vehicle (V2V), Vehicle-to-Infrastructure (V2I) or Vehicle- to-Road (V2R), Vehicle-to-Sensor (V2S), Vehicle-to-Human (V2H), Vehicle-to-Cellular (V2C), Vehicle-to-Grid (V2G), and Vehicle-to-Internet (V2I) connectivities. Accordingly, this paper proposes a novel planning scheme for internet connected and autonomous driving vehicles. Particularly, we present the principal components and how they should be distributed across this kind of architecture; i.e., identifying information flows, required exchanged data and basic functionalities required to build autonomous driving service as well as the holistic hardware and software architecture involving the in-car gateway.

Differential expression of miRNAs in the presence of B chromosome in the cichlid fish Astatotilapia latifasciata

Background B chromosomes (Bs) are extra elements observed in diverse eukaryotes, including animals, plants and fungi. Although Bs were first identified a century ago and have been studied in hundreds of species, their biology is still enigmatic. Recent advances in omics and big data technologies are revolutionizing the B biology field. These advances allow analyses of DNA, RNA, proteins and the construction of interactive networks for understanding the B composition and behavior in the cell. Several genes have been detected on the B chromosomes, although the interaction of B sequences and the normal genome remains poorly understood. Results We identified 727 miRNA precursors in the A. latifasciata genome, 66% which were novel predicted sequences that had not been identified before. We were able to report the A. latifasciata-specific miRNAs and common miRNAs identified in other fish species. For the samples carrying the B chromosome (B+), we identified 104 differentially expressed (DE) miRNAs that are down or upregulated compared to samples without B chromosome (B−) (p < 0.05). These miRNAs share common targets in the brain, muscle and gonads. These targets were used to construct a protein-protein-miRNA network showing the high interaction between the targets of differentially expressed miRNAs in the B+ chromosome samples. Among the DE-miRNA targets there are protein-coding genes reported for the B chromosome that are present in the protein-protein-miRNA network. Additionally, Gene Ontology (GO) terms related to nuclear matrix organization and response to stimulus are exclusive to DE miRNA targets of B+ samples. Conclusions This study is the first to report the connection of B chromosomes and miRNAs in a vertebrate species. We observed that the B chromosome impacts the miRNAs expression in several tissues and these miRNAs target several mRNAs involved with important biological processes.

Whole Exome Sequencing Reveals Pathogenic Variants in MYO3A, MYO15A and COL9A3, and Differential Frequencies in Ancestral Alleles in Hearing Impairment Genes Among Individuals from Cameroon

There is scarcity of known gene variants of Hearing Impairment (HI) in African populations. This knowledge deficit is ultimately affecting the development of genetic diagnoses. We used whole exome sequencing to investigate gene variants, pathways of interactive genes, and the fractions of ancestral over derived alleles for 159 HI genes, among 18 Cameroonian patients with non-syndromic HI (NSHI), and 129 ethnically matched controls. Pathogenic and likely pathogenic (PLP) variants were found in MYO3A, MYO15A and COL9A3, with a resolution rate of 50% (9/18 patients). The study identified significant genetic differentiation in novel population specific gene variants at FOXD4L2, DHRS2L6, RPL3L and VTN, between HI patients and controls. These gene variants are found in functional/co-expressed interactive networks with other known HI associated genes; and in the same pathways with VTN being a hub protein, i.e. focal adhesion pathway and regulation of the actin cytoskeleton (p values &lt; 0.05). The results suggest that these novel population specific gene variants are possible modifiers of the HI phenotypes. We found a high proportion of ancestral allele vs derived at low HI patients-specific minor allele frequency in range of 0.0 to 0.1. The results showed a relatively low pick up rate of PLP variants in known genes in this group of Cameroonian patients with NSHI. In addition, findings may signal an evolutionary enrichment of some variants of HI genes in patients, as the result of polygenic adaptation, and suggest the possibility of multigenic influence on the phenotype of congenital HI, which deserves further investigations.

Diversity, Interaction, and Bioprospecting of Plant-Associated Microbiomes

Plant-associated microbiomes have been suggested as pivotal for the growth and health of natural vegetation and agronomic plants. In this sense, plant-associated microbiomes harbor a huge diversity of microorganisms (such as bacteria and fungi) which can modulate the plant host response against pathogens and changing environmental conditions through a complex network of genetic, biochemical, physical, and metabolomics interactions. Advances on next-generation omic technologies have opened the possibility to unravel this complex microbial diversity and their interactive networks as never described before. In parallel, the develop of novel culture-dependent methods are also crucial to the study of the biology of members of plant-associated microbiomes and their bioprospecting as sources of bioactive compounds, or as tools to improve the productivity of agriculture. This Special Issue aims to motivate and collect recent studies which are focused on exploring the diversity and ecology of plant-associated microbiomes and their genetic and metabolic interactions with other microorganisms or their plant hosts, as well as their potential biotechnological applications in diverse fields, such as inoculants for agriculture.

Chromatin Dynamics and Transcriptional Control of Circadian Rhythms in Arabidopsis

Circadian rhythms pervade nearly all aspects of plant growth, physiology, and development. Generation of the rhythms relies on an endogenous timing system or circadian clock that generates 24-h oscillations in multiple rhythmic outputs. At its bases, the plant circadian function relies on dynamic interactive networks of clock components that regulate each other to generate rhythms at specific phases during the day and night. From the initial discovery more than 13 years ago of a parallelism between the oscillations in chromatin status and the transcriptional rhythms of an Arabidopsis clock gene, a number of studies have later expanded considerably our view on the circadian epigenome and transcriptome landscapes. Here, we describe the most recent identification of chromatin-related factors that are able to directly interact with Arabidopsis clock proteins to shape the transcriptional waveforms of circadian gene expression and clock outputs. We discuss how changes in chromatin marks associate with transcript initiation, elongation, and the rhythms of nascent RNAs, and speculate on future interesting research directions in the field.