MicroRNAs (miRNAs) are defined as small non-coding RNAs ~22 nt in length. They regulate gene expression at a post-transcriptional level through complementary base pairing with the target mRNA, ...leading to mRNA degradation and therefore blocking translation. In the last decade, the dysfunction of miRNAs has been related to the development and progression of many diseases. Currently, researchers need a method to identify precisely the miRNA targets, prior to applying experimental approaches that allow a better functional characterization of miRNAs in biological processes and can thus predict their effects. Computational prediction tools provide a rapid method to identify putative miRNA targets. However, since a large number of tools for the prediction of miRNA:mRNA interactions have been developed, all with different algorithms, the biological researcher sometimes does not know which is the best choice for his study and many times does not understand the bioinformatic basis of these tools. This review describes the biological fundamentals of these prediction tools, characterizes the main sequence-based algorithms, and offers some insights into their uses by biologists.
Twisted bilayer graphene is created by slightly rotating the two crystal networks in bilayer graphene with respect to each other. For small twist angles, the material undergoes a self-organized ...lattice reconstruction, leading to the formation of a periodically repeated domain
. The resulting superlattice modulates the vibrational
and electronic
structures within the material, leading to changes in the behaviour of electron-phonon coupling
and to the observation of strong correlations and superconductivity
. However, accessing these modulations and understanding the related effects are challenging, because the modulations are too small for experimental techniques to accurately resolve the relevant energy levels and too large for theoretical models to properly describe the localized effects. Here we report hyperspectral optical images, generated by a nano-Raman spectroscope
, of the crystal superlattice in reconstructed (low-angle) twisted bilayer graphene. Observations of the crystallographic structure with visible light are made possible by the nano-Raman technique, which reveals the localization of lattice dynamics, with the presence of strain solitons and topological points
causing detectable spectral variations. The results are rationalized by an atomistic model that enables evaluation of the local density of the electronic and vibrational states of the superlattice. This evaluation highlights the relevance of solitons and topological points for the vibrational and electronic properties of the structures, particularly for small twist angles. Our results are an important step towards understanding phonon-related effects at atomic and nanometric scales, such as Jahn-Teller effects
and electronic Cooper pairing
, and may help to improve device characterization
in the context of the rapidly developing field of twistronics
.
Heterostructures based on layering of two-dimensional (2D) materials such as graphene and hexagonal boron nitride represent a new class of electronic devices. Realizing this potential, however, ...depends critically on the ability to make high-quality electrical contact. Here, we report a contact geometry in which we metalize only the ID edge of a 2D graphene layer. In addition to outperforming conventional surface contacts, the edge-contact geometry allows a complete separation of the layer assembly and contact metallization processes. In graphene heterostructures, this enables high electronic performance, including low-temperature ballistic transport over distances longer than 15 micrometers, and room-temperature mobility comparable to the theoretical phonon-scattering limit. The edge-contact geometry provides new design possibilities for multilayered structures of complimentary 2D materials.
A faster rate of adaptive evolution of X‐linked genes compared with autosomal genes can be caused by the fixation of recessive or partially recessive advantageous mutations, due to the full ...expression of X‐linked mutations in hemizygous males. Other processes, including recombination rate and mutation rate differences between X chromosomes and autosomes, may also cause faster evolution of X‐linked genes. We review population genetics theory concerning the expected relative values of variability and rates of evolution of X‐linked and autosomal DNA sequences. The theoretical predictions are compared with data from population genomic studies of several species of Drosophila. We conclude that there is evidence for adaptive faster‐X evolution of several classes of functionally significant nucleotides. We also find evidence for potential differences in mutation rates between X‐linked and autosomal genes, due to differences in mutational bias towards GC to AT mutations. Many aspects of the data are consistent with the male hemizygosity model, although not all possible confounding factors can be excluded.
Genetic recombination associated with sexual reproduction increases the efficiency of natural selection by reducing the strength of Hill-Robertson interference. Such interference can be caused either ...by selective sweeps of positively selected alleles or by background selection (BGS) against deleterious mutations. Its consequences can be studied by comparing patterns of molecular evolution and variation in genomic regions with different rates of crossing over. We carried out a comprehensive study of the benefits of recombination in Drosophila melanogaster, both by contrasting five independent genomic regions that lack crossing over with the rest of the genome and by comparing regions with different rates of crossing over, using data on DNA sequence polymorphisms from an African population that is geographically close to the putatively ancestral population for the species, and on sequence divergence from a related species. We observed reductions in sequence diversity in noncrossover (NC) regions that are inconsistent with the effects of hard selective sweeps in the absence of recombination. Overall, the observed patterns suggest that the recombination rate experienced by a gene is positively related to an increase in the efficiency of both positive and purifying selection. The results are consistent with a BGS model with interference among selected sites in NC regions, and joint effects of BGS, selective sweeps, and a past population expansion on variability in regions of the genome that experience crossing over. In such crossover regions, the X chromosome exhibits a higher rate of adaptive protein sequence evolution than the autosomes, implying a Faster-X effect.
Recent epidemiological findings of associations between hearing loss (HL) and poorer mobility and higher falls risk have increased the demand for ecologically valid experimental research to determine ...the potential mechanisms underlying human hearing-balance relationships. This review provides an overview of the laboratory-based approaches to studying human balance, identifies crucial factors that should be considered to improve the ecological validity of hearing-balance research, and provides a critical review of the scientific literature to date on the effects of HL on balance. Most present studies can be subdivided into those that examine balance changes due to the effects of (1) auditory suppression in individuals with normal hearing, (2) HL with and without hearing aids, and (3) cochlear implants in children and adults. To allow for meaningful comparisons, we based our in-depth critical review on studies that met minimum criteria of having at least one objective kinetic or kinematic measure of standing balance during a two-legged stance with feet side-by-side, for at stance duration of at least 30 sec. With this minimum criterion in place, we found mixed evidence that hearing suppression, HL, or hearing devices affects postural stability, especially when other sensory information is available and/or reliable, and task demands are relatively low. However, hearing may become more important when multiple sensory systems become unreliable, task demands, or cognitive impairments are greater, or when sounds provide important auditory cues to assist with orientation or provide early detection of an impending balance disturbance. However, more research is clearly needed, because there is a wide range of technical and experimental differences and limitations observed across the present literature. To address these gaps, we have provided a number of recommendations and suggested priorities for future research to provide the ecologically valid, reliable, and reproducible evidence needed to uncover any potential relationships between HL, balance, and falls.
Genetic recombination affects levels of variability and the efficacy of selection because natural selection acting at one site affects evolutionary processes at linked sites. The variation in local ...recombination rates across the Drosophila genome provides excellent material for testing hypotheses concerning the evolutionary consequences of recombination. The current state of knowledge from studies of Drosophila genomics and population genetics is reviewed here. Selection at linked sites has influenced the relations between recombination rates and patterns of molecular variation and evolution, such that higher rates of recombination are associated with both higher levels of variability and a greater efficacy of selection. It seems likely that background selection against deleterious mutations is a major factor contributing to these patterns in genome regions in which crossing over is rare or absent, whereas selective sweeps of positively selected mutations probably play an important role in regions with crossing over.
Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by ...single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.
Many approaches for inferring adaptive molecular evolution analyze the unfolded site frequency spectrum (SFS), a vector of counts of sites with different numbers of copies of derived alleles in a ...sample of alleles from a population. Accurate inference of the high-copy-number elements of the SFS is difficult, however, because of misassignment of alleles as derived vs. ancestral. This is a known problem with parsimony using outgroup species. Here we show that the problem is particularly serious if there is variation in the substitution rate among sites brought about by variation in selective constraint levels. We present a new method for inferring the SFS using one or two outgroups that attempts to overcome the problem of misassignment. We show that two outgroups are required for accurate estimation of the SFS if there is substantial variation in selective constraints, which is expected to be the case for nonsynonymous sites in protein-coding genes. We apply the method to estimate unfolded SFSs for synonymous and nonsynonymous sites in a population of Drosophila melanogaster from phase 2 of the Drosophila Population Genomics Project. We use the unfolded spectra to estimate the frequency and strength of advantageous and deleterious mutations and estimate that ∼50% of amino acid substitutions are positively selected but that <0.5% of new amino acid mutations are beneficial, with a scaled selection strength of Nes ≈ 12.
The plant hormone jasmonate (JA) promotes the degradation of JASMONATE ZIM-DOMAIN (JAZ) proteins to relieve repression on diverse transcription factors (TFs) that execute JA responses. However, ...little is known about how combinatorial complexity among JAZ–TF interactions maintains control over myriad aspects of growth, development, reproduction, and immunity.
We used loss-of-function mutations to define epistatic interactions within the core JA signaling pathway and to investigate the contribution of MYC TFs to JA responses in Arabidopsis thaliana.
Constitutive JA signaling in a jaz quintuple mutant (jazQ) was largely eliminated by mutations that block JA synthesis or perception. Comparison of jazQ and a jazQ myc2 myc3 myc4 octuple mutant validated known functions of MYC2/3/4 in root growth, chlorophyll degradation, and susceptibility to the pathogen Pseudomonas syringae. We found that MYC TFs also control both the enhanced resistance of jazQ leaves to insect herbivory and restricted leaf growth of jazQ. Epistatic transcriptional profiles mirrored these phenotypes and further showed that triterpenoid biosynthetic and glucosinolate catabolic genes are up-regulated in jazQ independently of MYC TFs.
Our study highlights the utility of genetic epistasis to unravel the complexities of JAZ–TF interactions and demonstrates that MYC TFs exert master control over a JAZ-repressible transcriptional hierarchy that governs growth–defense balance.
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