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In-depth profiling of genetic variations in the gut microbiome is highly desired for understanding its functionality and impacts on host health and disease. Here, by harnessing the long read advantage provided by Oxford Nanopore Technology (ONT), we characterize fine-scale genetic variations of structural variations (SVs) in hundreds of gut microbiomes from healthy humans. ONT long reads dramatically improve the quality of metagenomic assemblies, enable reliable detection of a large, expanded set of structural variation types (notably including large insertions and inversions). We find SVs are highly distinct between individuals and stable within an individual, representing gut microbiome fingerprints that shape strain-level differentiations in function within species, complicating the associations to metabolites and host phenotypes such as blood glucose. In summary, our study strongly emphasizes that incorporating ONT reads into metagenomic analyses expands the detection scope of genetic variations, enables profiling strain-level variations in gut microbiome, and their intricate correlations with metabolome.

MicroRNA (miRNA) mediates post-transcriptional gene regulation and plays an important role in regulating the development of immune cells and in modulating innate and adaptive immune responses in mammals, including cattle. In the present study, we identified novel and differentially expressed miRNAs in peripheral blood from healthy and mastitis Holstein cattle by Solexa sequencing and bioinformatics. In total, 608 precursor hairpins (pre-miRNAs) encoding for 753 mature miRNAs were detected. Statistically, 173 unique miRNAs (of 753, 22.98%) were identified that had significant differential expression between healthy and mastitis Holstein cattle (P < 0.001). Most differentially expressed miRNAs (118 of 173, 68.21%) belonged to the chemokine signaling pathway involved in the immune responses. This study expands the number of miRNAs known to be expressed in cattle. The patterns of miRNAs expression differed significantly between the peripheral blood from healthy and mastitis Holstein cattle, which provide important information on mastitis in miRNAs expression. Diverse miRNAs may play an important role in the treatment of mastitis in Holstein cattle.

Functional nucleic acids lose activity when their sequence is prepared in the backbone architecture of a different genetic polymer. The only known exception to this rule is a subset of aptamers whose binding mechanism involves G-quadruplex formation. We refer to such examples as transliteration—a synthetic biology concept describing cases in which the phenotype of a nucleic acid molecule is retained when the genotype is written in a different genetic language. Here, we extend the concept of transliteration to include nucleic acid enzymes (XNAzymes) that mediate site-specific cleavage of an RNA substrate. We show that an in vitro selected 2′-fluoroarabino nucleic acid (FANA) enzyme retains catalytic activity when its sequence is prepared as α-l-threofuranosyl nucleic acid (TNA), and vice versa, a TNA enzyme that remains functional when its sequence is prepared as FANA. Structure probing with DMS supports the hypothesis that FANA and TNA enzymes having the same primary sequence can adopt similarly folded tertiary structures. These findings provide new insight into the sequence-structure-function paradigm governing biopolymer folding.

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To gain further insight into the molecular mechanism of bovine muscle development, we combined mass spectrometry characterization of proteins with Illumina deep sequencing of RNAs obtained from bovine longissimus muscle (LD) at prenatal and postnatal stages. For the proteomic study, each group of LD proteins was extracted and labeled using isobaric tags for relative and absolute quantitation (iTRAQ) method. Among the 1321 proteins identified from six samples, 390 proteins were differentially expressed in embryos at day 135 post-fertilization (Emb135d) vs. 30-month-old adult cattle (Emb135d vs. 30M) samples. Gene Ontology, Cluster of Orthologous Groups and Kyoto Encyclopedia of Genes and Genomes analyses were further conducted to better understand the different functions. Furthermore, we analyzed the relationship between transcript and protein regulation between samples by direct comparison of expression levels from transcriptomic and iTRAQ-based proteomics. Association results indicated that 1295 of 1321 proteins could be mapped to transcriptome sequencing data. This study provides the most comprehensive, targeted survey of bovine LD proteins to date and has shown the power of combining transcriptomic and proteomic approaches to provide molecular insights for understanding the developmental characteristics in bovine muscle, and even in other mammals.

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Oral vaccines have become a recent focus because of their potential significance in disease prevention and therapy. In the development of oral vaccine-based therapeutics, synthetic materials with tailorable structures and versatile functions can act as antigen conveyers with adjuvant effects, reduce the time cost for vaccine optimization, and provide high security and enhanced immunity. This review presents an overview of the current status of tailoring synthetic adjuvants for oral vaccination, modification strategies for producing effectors with specific structures and functions, enhancement of immune-associated efficiencies, including the barrier-crossing capability to protect antigens in the gastrointestinal tract, coordination of the antigens penetrating mucosa and cell barriers, targeting of concentrated antigens to immune-associated cells, and direct stimulation of immune cells. Finally, we focus on prospective synthetic adjuvants that facilitate the use of oral vaccines via two approaches, namely, in vivo antigen expression and cancer immunotherapy.