The microRNA (miR)183 cluster, which is comprised of miRs-183, -96 and -182, is also a miR family with sequence homology. Despite the strong similarity in the sequences of these miRs, minute differences in their seed sequences result in both overlapping and distinct messenger RNA targets, which are often within the same pathway. These miRs have tightly synchronized expression during development and are required for maturation of sensory organs. In comparison to their defined role in normal development, the miR-183 family is frequently highly expressed in a variety of non-sensory diseases, including cancer, neurological and auto-immune disorders. Here, we discuss the conservation of the miR-183 cluster and the functional role of this miR family in normal development and diseases. We also describe the regulation of vital cellular pathways by coordinated expression of these miR siblings. This comprehensive review sheds light on the likely reasons why the genomic organization and seeming redundancy of the miR-183 family cluster was conserved through 600 million years of evolution.

There is a common interest for studying xeno-nucleic acid systems in the fields of synthetic biology and the origin of life, in particular, those with an engineered backbone and possessing novel properties. Along this line, we have investigated xylonucleic acid (XyloNA) containing a potentially prebiotic xylose sugar (a 3'-epimer of ribose) in its backbone. Herein, we report for the first time the synthesis of four XyloNA nucleotide building blocks and the assembly of XyloNA oligonucleotides containing all the natural nucleobases. A detailed investigation of pairing and structural properties of XyloNAs in comparison to DNA/RNA has been performed by thermal UV-melting, CD, and solution state NMR spectroscopic studies. XyloNA has been shown to be an orthogonal self-pairing system which adopts a slightly right-handed extended helical geometry. Our study on one hand, provides understanding for superior structure-function (-pairing) properties of DNA/RNA over XyloNA for selection as an informational polymer in the prebiotic context, while on the other hand, finds potential of XyloNA as an orthogonal genetic system for application in synthetic biology.

PX-DNA is a four-stranded DNA structure that has been implicated in the recognition of homology, either continuously, or in an every-other-half-turn fashion. Some of the structural features of the molecule have been noted previously, but the structure requires further characterization. Here, we report atomic force microscopic characterization of PX molecules that contain periodically placed biotin groups, enabling the molecule to be labeled by streptavidin molecules at these sites. In comparison with conventional double stranded DNA and with antiparallel DNA double crossover molecules, it is clear that PX-DNA is a more dynamic structure. Furthermore, the spacing between the nucleotide pairs along the helix axis is shorter, suggesting a mixed B/A structure. Circular dichroism spectroscopy indicates unusual features in the PX molecule that are absent in both the molecules to which it is compared.

H/ACA RNA-guided ribonucleoprotein particle (RNP), the most complicated RNA pseudouridylase so far known, uses H/ACA guide RNA for substrate capture and four proteins (Cbf5, Nop10, L7Ae and Gar1) for pseudouridylation. Although it was shown that Gar1 not only facilitates the product release, but also enhances the catalytic activity, the chemical role that Gar1 plays in this complicated machinery is largely unknown. Kinetics measurement on Pyrococcus furiosus RNPs at different temperatures making use of fluorescence anisotropy showed that Gar1 reduces the catalytic barrier through affecting the activation entropy instead of enthalpy. Site-directed mutagenesis combined with molecular dynamics simulations demonstrated that V149 in the thumb loop of Cbf5 is critical in placing the target uridine to the right position toward catalytic D85 of Cbf5. The enzyme elegantly aligns the position of uridine in the catalytic site with the help of Gar1. In addition, conversion of uridine to pseudouridine results in a rigid syn configuration of the target nucleotide in the active site and causes Gar1 to pull out the thumb. Both factors guarantee the efficient release of the product.

With the development of High-Throughput Sequencing (HTS) thousands of human genomes have now been sequenced. Whenever different studies analyze the same genome they usually agree on the amount of single-nucleotide polymorphisms, but differ dramatically on the number of insertion and deletion variants (indels). Furthermore, there is evidence that indels are often severely under-reported. In this manuscript we derive the total number of indel variants in a human genome by combining data from different sequencing technologies, while assessing the indel detection accuracy. Our estimate of approximately 1 million indels in a Yoruban genome is much higher than the results reported in several recent HTS studies. We identify two key sources of difficulties in indel detection: the insufficient coverage, read length or alignment quality; and the presence of repeats, including short interspersed elements and homopolymers/dimers. We quantify the effect of these factors on indel detection. The quality of sequencing data plays a major role in improving indel detection by HTS methods. However, many indels exist in long homopolymers and repeats, where their detection is severely impeded. The true number of indel events is likely even higher than our current estimates, and new techniques and technologies will be required to detect them.

Due to the helical structure of DNA the process of DNA replication is topologically complex. Freshly replicated DNA molecules are catenated with each other and are frequently knotted. For proper functioning of DNA it is necessary to remove all of these entanglements. This is done by DNA topoisomerases that pass DNA segments through each other. However, it has been a riddle how DNA topoisomerases select the sites of their action. In highly crowded DNA in living cells random passages between contacting segments would only increase the extent of entanglement. Using molecular dynamics simulations we observed that in actively supercoiled DNA molecules the entanglements resulting from DNA knotting or catenation spontaneously approach sites of nicks and gaps in the DNA. Type I topoisomerases, that preferentially act at sites of nick and gaps, are thus naturally provided with DNA–DNA juxtapositions where a passage results in an error-free DNA unknotting or DNA decatenation.

Recent chromosome conformation capture (3C) derived techniques have revealed that topologically associating domain (TAD) is a pervasive element in chromatin three-dimensional (3D) organization. However, there is currently no parameter to quantitatively measure the structural characteristics of TADs, thus obscuring our understanding on the structural and functional differences among TADs. Based on our finding that there exist intrinsic chromatin interaction patterns in TADs, we define a theoretical parameter, called aggregation preference (AP), to characterize TAD structures by capturing the interaction aggregation degree. Applying this defined parameter to 11 Hi-C data sets generated by both traditional and in situ Hi-C experimental pipelines, our analyses reveal that heterogeneous structures exist among TADs, and this structural heterogeneity is significantly correlated to DNA sequences, epigenomic signals and gene expressions. Although TADs can be stable in genomic positions across cell lines, structural comparisons show that a considerable number of stable TADs undergo significantly structural rearrangements during cell changes. Moreover, the structural change of TAD is tightly associated with its transcription remodeling. Altogether, the theoretical parameter defined in this work provides a quantitative method to link structural characteristics and biological functions of TADs, and this linkage implies that chromatin interaction pattern has the potential to mark transcription activity in TADs.

Recently, several experimental techniques have emerged for probing RNA structures based on high-throughput sequencing. However, most secondary structure prediction tools that incorporate probing data are designed and optimized for particular types of experiments. For example, RNAstructure-Fold is optimized for SHAPE data, while SeqFold is optimized for PARS data. Here, we report a new RNA secondary structure prediction method, restrained MaxExpect (RME), which can incorporate multiple types of experimental probing data and is based on a free energy model and an MEA (maximizing expected accuracy) algorithm. We first demonstrated that RME substantially improved secondary structure prediction with perfect restraints (base pair information of known structures). Next, we collected structure-probing data from diverse experiments (e.g. SHAPE, PARS and DMS-seq) and transformed them into a unified set of pairing probabilities with a posterior probabilistic model. By using the probability scores as restraints in RME, we compared its secondary structure prediction performance with two other well-known tools, RNAstructure-Fold (based on a free energy minimization algorithm) and SeqFold (based on a sampling algorithm). For SHAPE data, RME and RNAstructure-Fold performed better than SeqFold, because they markedly altered the energy model with the experimental restraints. For high-throughput data (e.g. PARS and DMS-seq) with lower probing efficiency, the secondary structure prediction performances of the tested tools were comparable, with performance improvements for only a portion of the tested RNAs. However, when the effects of tertiary structure and protein interactions were removed, RME showed the highest prediction accuracy in the DMS-accessible regions by incorporating in vivo DMS-seq data.

Journal of the American Chemical SocietyDOI: 10.1021/jacs.5b06336

Ten years ago, Katrina, a category 5 hurricane at peak strength, slammed into New Orleans. Its associated storm surge breached the extensive levee system that had protected the city. Nearly 2000 residents died, and damages exceeded $100 billion. The storm remains the costliest natural disaster in U.S. history, and the resulting economic, social, and environmental turmoil led to the largest mass migration since the U.S. Civil War. A distinguished panel* of scientists and engineers who had been on the scene of Katrina was convened on the eve of the 10th anniversary of this event to address the question: Are American cities better prepared for the next major hurricane? Author: Marcia McNutt

In science news around the world, the IS group destroys an ancient temple in Palmyra, Syria, the U.S. Food and Drug Administration approves a "female Viagra" drug, eight protestors are arrested in Hawaii attempting to block construction of the Daniel K. Inouye Solar Telescope, a new quantum processor breaks the "1000-qubit barrier," and more. Also, the National Oceanic and Atmospheric Administration declares the deaths of 30 large whales in the Gulf of Alaska since May an "unusual mortality event," triggering a focused investigation into the cause of the deaths. And Science chats with Jorge Cham, creator of the comic Piled Higher and Deeper (PHD), about his new, upcoming movie.

Brazilian scientists are facing one of the nation's worst funding climates in decades. Battling a slumping economy and debt, Brazil's federal government has taken an ax to spending, and it isn't sparing science. President Dilma Rousseff's administration has cut by 25% the Ministry of Science's projected 2015 budget, and sliced 9% from the budget of the Ministry of Education, which plays an important role in funding graduate students. Research agencies are withholding money for grants that have already been awarded, and have canceled or postponed new calls for proposals. And Rousseff is redirecting funds once earmarked largely for research to send Brazilian students abroad to study. The funding climate is "the worst in 20 years," says Helena Nader, president of the Brazilian Society for the Advancement of Science. At the root of the problem are changes in how Brazil's government spends the royalties generated by Brazil's lucrative offshore oil fields, which have been a major source of funding for science and technology development. In recent years, Brazil's government has redirected much of the oil revenue to other priorities, including health care and education. Author: Herton Escobar

The largest effort yet to replicate psychology studies has yielded both good and bad news. On the down side, of the 100 prominent papers analyzed, only 39% could be replicated unambiguously, as a group of 270 researchers describes on page 943. On the up side, despite the sobering results, the effort seems to have drawn little of the animosity that greeted a similar replication effort last year. This time around, even some of the original authors see the replications as a useful addition to their own research. "This is how science works," says Joshua Correll, a psychologist at the University of Colorado, Boulder, and one of the authors whose results could not be replicated. "How else will we converge on the truth? Really, the surprising thing is that this kind of systematic attempt at replication is not more common." That's encouraging news to Brian Nosek, a psychologist at the University of Virginia in Charlottesville who led the mass replication effort, which began in 2011 with the goal of putting psychological science on more rigorous experimental footing. Author: John Bohannon

It is famous for robbing Lou Gehrig of his life and Stephen Hawking of his mobility and voice, but just how amyotrophic lateral sclerosis (ALS) destroys motor neurons in the brain and spinal cord remains a mystery. Now, scientists are converging on an explanation, at least for a fraction of the ALS cases caused by a mutation also associated with a kind of dementia. In cells with the mutation, the new work shows, pores in the membrane separating the nucleus and cytoplasm become clogged, preventing vital molecules from passing through and creating a fatal cellular traffic jam. For now, the work applies only to the mutation dubbed C9orf72—a DNA stutter in which a short nucleotide sequence, GGGGCC, is repeated hundreds to thousands of times in a gene on chromosome 9. Nor do the multiple labs reporting results this week agree on exactly what plugs those nuclear pores and how the cells die. Still, many in the field are calling the work a major breakthrough, and say the findings could point to new therapies, as well as a novel mechanism for neurodegeneration. Author: Emily Underwood

Nuclear fusion has always required titanic machines and vast amounts of public money—and success is always decades away. Now, a privately funded company has taken what some physicists say is a significant step toward mastering fusion energy with a smaller, cheaper, faster approach. Tri Alpha Energy announced this week that it has built a machine that forms a ball of gas—superheated to about 10 million degrees Celsius—and holds it steady for 5 milliseconds without decaying. Those conditions are well short of what is needed for fusion, but the feat shows for the first time that Tri Alpha's unorthodox approach can trap hot fusion gas in a steady state. Now, the scientists hope to scale up the technique toward times and temperatures that cause atomic nuclei in the gas to fuse together, releasing energy. Author: Daniel Clery

With more than 25,000 species, orchids are the largest group of plants. A new family tree shows how they owe their diversity to a series of innovations that individually or jointly touched off explosions of new species. The pace of diversification rose after orchids developed a way to lump their pollen into balls called pollinia, which allowed them to exclusively rely on certain insect species for pollination. Many lineages benefited from the evolution of a kind of water-saving photosynthesis. A shift to living in trees opened up many niches, as did a move into tropical mountains such as the Andes. Author: Erik Stokstad

In North America, crayfish have diversified into roughly 400 species—two-thirds of the world's total—and live mainly in the southeast. Biologists estimate nearly half of U.S. species are imperiled, whereas about a third of the world's crayfish are. Spurred by growing concerns that pollution, habitat destruction, and other threats are placing many crayfish species in harm's way, federal officials are taking a hard look at whether to give legal protection to two: the Guyandotte River crayfish found in southern West Virginia and the Big Sandy crayfish found in Kentucky, West Virginia, and Virginia. If the listings go through, a broad range of economically important activities that affect the crayfish, including mining, logging, and recreation, could feel an impact. So government officials are proceeding with care, seeking to learn as much as possible about the enigmatic invertebrates before making decisions—and they are asking researchers like West Liberty University's Zachary Loughman for help. Author: Emily DeMarco