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LncRNAs (long non-coding RNAs) are pervasively transcribed in the human genome and also extensively involved in a variety of essential biological processes and human diseases. The comprehensive annotation of human lncRNAs is of great significance in navigating the functional landscape of the human genome and deepening the understanding of the multi-featured RNA world. However, the unique characteristics of lncRNAs as well as their enormous quantity have complicated and challenged the annotation of lncRNAs. Advances in high-throughput sequencing technologies give rise to a large volume of omics data that are generated at an unprecedented rate and scale, providing possibilities in the identification, characterization and functional annotation of lncRNAs. Here, we review the recent important discoveries of human lncRNAs through analysis of various omics data and summarize specialized lncRNA database resources. Moreover, we highlight the multi-omics integrative analysis as a powerful strategy to efficiently discover and characterize the functional lncRNAs and elucidate their potential molecular mechanisms.
Hallux valgus (HV) is a progressive foot deformity in which the first metatarsophalangeal (MTP) joint is affected. The relationship between the dome height of the first metatarsal head and the HV deformity has not been studied previously. click here This study aimed to investigate a possible relation of the dome height of the first metatarsal head with articular alignment and the hallux valgus angle (HVA), which is frequently used to evaluate HV.
A total of 129 feet of 68 patients were included in the study. Anteroposterior digital radiographic images of the foot taken in a weightbearing, standing position were used to assess the HVA, dome height, and shape of the first metatarsal head and the alignment of the MTP joint. The dome height of the first metatarsal head is the vertical distance from the base to the highest point of the articular surface doming. The alignment was categorized into three groups aligned, deviated, and subluxated. Patients were assigned into three groups based on the HVA Normal, Mild HV and Moderate HV.
A statistically significant, positive correlation was found between the HVA and the dome height of the first metatarsal head (r = 0.293, P = 0.001 and P < 0.05). The dome height was significantly lower in the patients with a normal HVA than those with a high HVA (P1 = 0.042, P2 = 0.039 and P < 0.05, respectively). The dome height of the first metatarsal head was found significantly higher in feet with subluxation, compared to feet aligned and deviated (P1 = 0.001; P2 = 0.0089 and P < 0.05, respectively).
Our study results suggest that HV deformity may be related to an increased dome height and the measurement of the dome height of the first metatarsal head might be used to evaluate an anatomic tendency toward HV development.
Our study results suggest that HV deformity may be related to an increased dome height and the measurement of the dome height of the first metatarsal head might be used to evaluate an anatomic tendency toward HV development.Mass photometry is a recently developed methodology capable of measuring the mass of individual proteins under solution conditions. Here, we show that this approach is equally applicable to nucleic acids, enabling their facile, rapid and accurate detection and quantification using sub-picomoles of sample. The ability to count individual molecules directly measures relative concentrations in complex mixtures without need for separation. Using a dsDNA ladder, we find a linear relationship between the number of bases per molecule and the associated imaging contrast for up to 1200 bp, enabling us to quantify dsDNA length with up to 2 bp accuracy. These results introduce mass photometry as an accurate, rapid and label-free single molecule method complementary to existing DNA characterization techniques.Mitochondrial gene expression in African trypanosomes and other trypanosomatid pathogens requires a U-nucleotide specific insertion/deletion-type RNA-editing reaction. The process is catalyzed by a macromolecular protein complex known as the editosome. Editosomes are restricted to the trypanosomatid clade and since editing is essential for the parasites, the protein complex represents a near perfect target for drug intervention strategies. Here, we report the development of an improved in vitro assay to monitor editosome function. The test system utilizes fluorophore-labeled substrate RNAs to analyze the processing reaction by automated, high-throughput capillary electrophoresis (CE) in combination with a laser-induced fluorescence (LIF) readout. We optimized the assay for high-throughput screening (HTS)-experiments and devised a multiplex fluorophore-labeling regime to scrutinize the U-insertion/U-deletion reaction simultaneously. The assay is robust, it requires only nanogram amounts of materials and it meets all performance criteria for HTS-methods. As such the test system should be helpful in the search for trypanosome-specific pharmaceuticals.GapR is a nucleoid-associated protein that is an essential regulator of chromosome replication in the cell cycle model Caulobacter crescentus. Here, we demonstrate that free GapR is a homotetramer, but not a dimer as previously reported (Guo et al., Cell 175 583-597, 2018). We have determined the crystal structure of GapR in complex with a 10-bp A-tract DNA, which has an open tetrameric conformation, different from the closed clamp conformation in the previously reported crystal structure of GapR/DNA complex. The free GapR adopts multiple conformations in dynamic exchange equilibrium, with the major conformation resembling the closed tetrameric conformation, while the open tetrameric conformation is a representative of minor conformers. As it is impossible for the circular genomic DNA to get into the central DNA binding tunnel of the major conformation, we propose that GapR initially binds DNA through the open conformation, and then undergoes structural rearrangement to form the closed conformation which fully encircles the DNA. GapR prefers to bind DNA with 10-bp consecutive A/T base pairs nonselectively (Kd ∼12 nM), while it can also bind GC-rich DNA sequence with a reasonable affinity of about 120 nM. Besides, our results suggest that GapR binding results in widening the minor groove of AT-rich DNA, instead of overtwisting DNA.
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