Sox2-Dependent 3D Chromatin Interactomes in Transcription, Neural Stem Cell Proliferation and Neurodevelopmental Diseases.

In our article, we asked whether Sox2, a transcription factor important in brain development and disease, is involved in gene regulation through its action on long-range interactions between promoters and distant enhancers. Our findings highlight that Sox2 shapes a genome-wide network of promoter-enhancer interactions, acting by direct binding to these elements. Sox2 loss affects the three-dimensional (3D) genome and decreases the activity of a subset of genes involved in Sox2-bound interactions. At least one of such downregulated genes, Socs3, is critical for long-term neural stem cell maintenance. These results point to the possibility of identifying a transcriptional network downstream to Sox2, and involved in neural stem cell maintenance. In addition, interacting Sox2-bound enhancers are often connected to genes which are relevant, in man, to neurodevelopmental disease; this may facilitate the detection of functionally relevant mutations in regulatory elements in man, contributing to neural disease

Graphene-Based Biosensors for Detection of Composite Vibrational Fingerprints in the Mid-Infrared Region.

In this study, a label-free multi-resonant graphene-based biosensor with periodic graphene nanoribbons is proposed for detection of composite vibrational fingerprints in the mid-infrared range. The multiple vibrational signals of biomolecules are simultaneously enhanced and detected by different resonances in the transmission spectrum. Each of the transmission dips can be independently tuned by altering the gating voltage applied on the corresponding graphene nanoribbon. Geometric parameters are investigated and optimized to obtain excellent sensing performance. Limit of detection is also evaluated in an approximation way. Besides, the biosensor can operate in a wide range of incident angles. Electric field intensity distributions are depicted to reveal the physical insight. Moreover, another biosensor based on periodic graphene nanodisks is further proposed, whose performance is insensitive to the polarization of incidence. Our research may have a potential for designing graphene-based biosensor used in many promising bioanalytical and pharmaceutical applications

L-4, a Well-Tolerated and Orally Active Inhibitor of Hedgehog Pathway, Exhibited Potent Anti-tumor Effects Against Medulloblastoma in vitro and in vivo

Inhibition of aberrant Hedgehog (Hh) pathway had been proved to be a promising therapeutic intervention in cancers like basal cell carcinoma (BCC), medulloblastoma (MB), and so on. Two drugs (Vismodegib, Sonidegib) were approved to treat BCC and more inhibitors are in clinical investigation. However, the adverse effects and drug resistance restricted the use of Hh inhibitors. In the present study, 61 synthesized compounds containing central backbone of phthalazine or dimethylpyridazine were screened as candidates of new Hh signaling inhibitors by performing dual luciferase reporter assay. Among the compounds, L-4 exhibited an IC50 value of 2.33 nM in the Shh-Light II assay. L-4 strongly inhibited the Hh pathway in vitro and blocked the Hh pathway by antagonizing the smoothened receptor (Smo). Remarkably, L-4 could significantly suppress the Hh pathway activity provoked by Smo mutant (D473H) which showed strong resistant properties to existing drugs such as Vismodegib. Orally administered L-4 exhibited prominent dose-dependent anti-tumor efficacy in vivo in Ptch+/-; p53-/- MB allograft model. Furthermore, L-4 showed good tolerance in acute toxicity test using ICR mice. These evidences indicated that L-4 was a potent, well-tolerated, orally active inhibitor of Hedgehog pathway, and might be a promising candidate in development of Hh-targeted anti-cancer drugs

Combined Genomic, Transcriptomic, Proteomic, and Physiological Characterization of the Growth of Pecoramyces sp. F1 in Monoculture and Co-culture With a Syntrophic Methanogen

In this study, the effects of a syntrophic methanogen on the growth of Pecoramyces sp. F1 was investigated by characterizing fermentation profiles, as well as functional genomic, transcriptomic, and proteomic analysis. The estimated genome size, GC content, and protein coding regions of strain F1 are 106.83 Mb, 16.07%, and 23.54%, respectively. Comparison of the fungal monoculture with the methanogen co-culture demonstrated that during the fermentation of glucose, the co-culture initially expressed and then down-regulated a large number of genes encoding both enzymes involved in intermediate metabolism and plant cell wall degradation. However, the number of up-regulated proteins doubled at the late-growth stage in the co-culture. In addition, we provide a mechanistic understanding of the metabolism of this fungus in co-culture with a syntrophic methanogen. Further experiments are needed to explore this interaction during degradation of more complex plant cell wall substrates

REMEDIAL APPLICATIONS OF SILENCING RIBONUCLEIC ACIDS AND MODALITIES FOR ITS DELIVERY TO THE KIDNEYS - A REVIEW

Background: The Kidney has been the target organ for the delivery of silencing ribonucleic acids (silencing RNA) administered systemically in comparison to other body tissues. Materials and method: In this review, we discussed different approaches made to delivering proteins to the kidneys in different conditions like normal and pathological defects. Data from clinical experiments have been used to discuss and support the administration of silencing RNA for the treatment of kidney diseases. Results: Results were achieved using the available genome wide RNA libraries. Conclusion: The research results are helpful in application to 3D and conventional models to find the involvement of signal pathways in kidney diseases

Insights into the vertical stratification of microbial ecological roles across the deepest seawater column on Earth

The Earth’s oceans are a huge body of water with physicochemical properties and microbial community profiles that change with depth, which in turn influences their biogeochemical cycling potential. The differences between microbial communities and their functional potential in surface to hadopelagic water samples are only beginning to be explored. Here, we used metagenomics to investigate the microbial communities and their potential to drive biogeochemical cycling in seven different water layers down the vertical profile of the Challenger Deep (0–10,500 m) in the Mariana Trench, the deepest natural point in the Earth’s oceans. We recovered 726 metagenome-assembled genomes (MAGs) affiliated to 27 phyla. Overall, biodiversity increased in line with increased depth. In addition, the genome size of MAGs at ≥4000 m layers was slightly larger compared to those at 0–2000 m. As expected, surface waters were the main source of primary production, predominantly from Cyanobacteria. Intriguingly, microbes conducting an unusual form of nitrogen metabolism were identified in the deepest waters (>10,000 m), as demonstrated by an enrichment of genes encoding proteins involved in dissimilatory nitrate to ammonia conversion (DNRA), nitrogen fixation and urea transport. These likely facilitate the survival of ammonia-oxidizing archaea α lineage, which are typically present in environments with a high ammonia concentration. In addition, the microbial potential for oxidative phosphorylation and the glyoxylate shunt was enhanced in >10,000 m waters. This study provides novel insights into how microbial communities and their genetic potential for biogeochemical cycling differs through the Challenger deep water column, and into the unique adaptive lifestyle of microbes in the Earth’s deepest seawater

Anaerobic Fungi Isolated From Bactrian Camel Rumen Contents Have Strong Lignocellulosic Bioconversion Potential

This study aims to obtain anaerobic fungi from the rumen and fecal samples and investigates their potential for lignocellulosic bioconversion. Multiple anaerobic strains were isolated from rumen contents (CR1–CR21) and fecal samples (CF1–CF10) of Bactrian camel using the Hungate roll tube technique. After screening for fiber degradability, strains from rumen contents (Oontomyces sp. CR2) and feces (Piromyces sp. CF9) were compared with Pecoramyces sp. F1 (earlier isolated from goat rumen, having high CAZymes of GHs) for various fermentation and digestion parameters. The cultures were fermented with different substrates (reed, alfalfa stalk, Broussonetia papyrifera leaves, and Melilotus officinalis) at 39°C for 96 h. The Oontomyces sp. CR2 had the highest total gas and hydrogen production from most substrates in the in vitro rumen fermentation system and also had the highest digestion of dry matter, neutral detergent fiber, acid detergent fiber, and cellulose present in most substrates used. The isolated strains provided higher amounts of metabolites such as lactate, formate, acetate, and ethanol in the in vitro rumen fermentation system for use in various industrial applications. The results illustrated that anaerobic fungi isolated from Bactrian camel rumen contents (Oontomyces sp. CR2) have the highest lignocellulosic bioconversion potential, suggesting that the Bactrian camel rumen could be a good source for the isolation of anaerobic fungi for industrial applications