Efficient use of accessibility in microRNA target prediction

Considering accessibility of the 3′UTR is believed to increase the precision of microRNA target predictions. We show that, contrary to common belief, ranking by the hybridization energy or by the sum of the opening and hybridization energies, used in currently available algorithms, is not an efficient way to rank predictions. Instead, we describe an algorithm which also considers only the accessible binding sites but which ranks predictions according to over-representation. When compared with experimentally validated and refuted targets in the fruit fly and human, our algorithm shows a remarkable improvement in precision while significantly reducing the computational cost in comparison with other free energy based methods. In the human genome, our algorithm has at least twice higher precision than other methods with their default parameters. In the fruit fly, we find five times more validated targets among the top 500 predictions than other methods with their default parameters. Furthermore, using a common statistical framework we demonstrate explicitly the advantages of using the canonical ensemble instead of using the minimum free energy structure alone. We also find that ‘naïve' global folding sometimes outperforms the local folding approac

Evidence of topological superconductivity in planar Josephson junctions

Majorana zero modes are quasiparticle states localized at the boundaries of topological superconductors that are expected to be ideal building blocks for fault-tolerant quantum computing. Several observations of zero-bias conductance peaks measured in tunneling spectroscopy above a critical magnetic field have been reported as experimental indications of Majorana zero modes in superconductor/semiconductor nanowires. On the other hand, two dimensional systems offer the alternative approach to confine Ma jorana channels within planar Josephson junctions, in which the phase difference {\phi} between the superconducting leads represents an additional tuning knob predicted to drive the system into the topological phase at lower magnetic fields. Here, we report the observation of phase-dependent zero-bias conductance peaks measured by tunneling spectroscopy at the end of Josephson junctions realized on a InAs/Al heterostructure. Biasing the junction to {\phi} ~ {\pi} significantly reduces the critical field at which the zero-bias peak appears, with respect to {\phi} = 0. The phase and magnetic field dependence of the zero-energy states is consistent with a model of Majorana zero modes in finite-size Josephson junctions. Besides providing experimental evidence of phase-tuned topological superconductivity, our devices are compatible with superconducting quantum electrodynamics architectures and scalable to complex geometries needed for topological quantum computing.Comment: main text and extended dat

PACCMIT/PACCMIT-CDS: identifying microRNA targets in 3′ UTRs and coding sequences

The purpose of the proposed web server, publicly available at http://paccmit.epfl.ch, is to provide a user-friendly interface to two algorithms for predicting messenger RNA (mRNA) molecules regulated by microRNAs: (i) PACCMIT (Prediction of ACcessible and/or Conserved MIcroRNA Targets), which identifies primarily mRNA transcripts targeted in their 3′ untranslated regions (3′ UTRs), and (ii) PACCMIT-CDS, designed to find mRNAs targeted within their coding sequences (CDSs). While PACCMIT belongs among the accurate algorithms for predicting conserved microRNA targets in the 3′ UTRs, the main contribution of the web server is 2-fold: PACCMIT provides an accurate tool for predicting targets also of weakly conserved or non-conserved microRNAs, whereas PACCMIT-CDS addresses the lack of similar portals adapted specifically for targets in CDS. The web server asks the user for microRNAs and mRNAs to be analyzed, accesses the precomputed P-values for all microRNA–mRNA pairs from a database for all mRNAs and microRNAs in a given species, ranks the predicted microRNA–mRNA pairs, evaluates their significance according to the false discovery rate and finally displays the predictions in a tabular form. The results are also available for download in several standard formats

Optimization by Response Surface Methodology (RSM) of the Kharasch−Sosnovsky Oxidation of Valencene

Response surface methodology (RSM) has been employed to model and optimize the Kharasch−Sosnovsky allylic oxidation of valencene. The detailed effects of the amounts of oxidant, substrate, copper catalyst, 1,8- diazabicyclo[5.4.0]undec-7-ene (DBU), and temperature have been studied. The concentration of substrate and quantity of oxidant have been determined as the most significant variables. The interaction effects on the yield have been investigated using a three-level full-factorial design. The yield of benzoyloxyvalencene has been improved to 99%. Analysis of variance (ANOVA) has been used to evaluate the goodness of fit of the model

Mitochondrial phylogeography and demographic history of the Vicuña: implications for conservation

The vicuña (Vicugna vicugna; Miller, 1924) is a conservation success story, having recovered from near extinction in the 1960s to current population levels estimated at 275 000. However, lack of information about its demographic history and genetic diversity has limited both our understanding of its recovery and the development of science-based conservation measures. To examine the evolution and recent demographic history of the vicuña across its current range and to assess its genetic variation and population structure, we sequenced mitochondrial DNA from the control region (CR) for 261 individuals from 29 populations across Peru, Chile and Argentina. Our results suggest that populations currently designated as Vicugna vicugna vicugna and Vicugna vicugna mensalis comprise separate mitochondrial lineages. The current population distribution appears to be the result of a recent demographic expansion associated with the last major glacial event of the Pleistocene in the northern (18 to 22°S) dry Andes 14–12 000 years ago and the establishment of an extremely arid belt known as the 'Dry Diagonal' to 29°S. Within the Dry Diagonal, small populations of V. v. vicugna appear to have survived showing the genetic signature of demographic isolation, whereas to the north V. v. mensalis populations underwent a rapid demographic expansion before recent anthropogenic impacts

Efficient use of accessibility in microRNA target prediction

Considering accessibility of the 3′UTR is believed to increase the precision of microRNA target predictions. We show that, contrary to common belief, ranking by the hybridization energy or by the sum of the opening and hybridization energies, used in currently available algorithms, is not an efficient way to rank predictions. Instead, we describe an algorithm which also considers only the accessible binding sites but which ranks predictions according to over-representation. When compared with experimentally validated and refuted targets in the fruit fly and human, our algorithm shows a remarkable improvement in precision while significantly reducing the computational cost in comparison with other free energy based methods. In the human genome, our algorithm has at least twice higher precision than other methods with their default parameters. In the fruit fly, we find five times more validated targets among the top 500 predictions than other methods with their default parameters. Furthermore, using a common statistical framework we demonstrate explicitly the advantages of using the canonical ensemble instead of using the minimum free energy structure alone. We also find that ‘naïve’ global folding sometimes outperforms the local folding approach

Optimal Use of Conservation and Accessibility Filters in MicroRNA Target Prediction

It is generally accepted that filtering microRNA (miRNA) target predictions by conservation or by accessibility can reduce the false discovery rate. However, these two strategies are usually not exploited in a combined and flexible manner. Here, we introduce PACCMIT, a flexible method that filters miRNA binding sites by their conservation, accessibility, or both. The improvement in performance obtained with each of these three filters is demonstrated on the prediction of targets for both i) highly and ii) weakly conserved miRNAs, i.e., in two scenarios in which the miRNA-target interactions are subjected to different evolutionary pressures. We show that in the first scenario conservation is a better filter than accessibility (as both sensitivity and precision are higher among the top predictions) and that the combined filter improves performance of PACCMIT even further. In the second scenario, on the other hand, the accessibility filter performs better than both the conservation and combined filters, suggesting that the site conservation is not equally effective in rejecting false positive predictions for all miRNAs. Regarding the quality of the ranking criterion proposed by Robins and Press and used in PACCMIT, it is shown that top ranking interactions correspond to more downregulated proteins than do the lower ranking interactions. Comparison with several other target prediction algorithms shows that the ranking of predictions provided by PACCMIT is at least as good as the ranking generated by other conservation-based methods and considerably better than the energy-based ranking used in other accessibility-based methods

Uncovering the stellar structure of the dusty star-forming galaxy GN20 at z=4.055 with MIRI/JWST

Luminous infrared galaxies at high redshifts ($z$>4) include extreme starbursts that build their stellar mass over short periods of time (>100 Myr). These galaxies are considered to be the progenitors of massive quiescent galaxies at intermediate redshifts ($z\sim$2) but their stellar structure and buildup is unknown. Here, we present the first spatially resolved near-infrared imaging of GN20, one of the most luminous dusty star-forming galaxies known to date, observed at an epoch when the Universe was only 1.5 Gyr old. The 5.6$\mu$m image taken with the JWST Mid-Infrared Instrument (MIRI/JWST) shows that GN20 is a very luminous galaxy (M$_\mathrm{1.1\mu m,AB}$=$-$25.01), with a stellar structure composed of a conspicuous central source and an extended envelope. The central source is an unresolved nucleus that carries 9% of the total flux. The nucleus is co-aligned with the peak of the cold dust emission, and offset by 3.9 kpc from the ultraviolet stellar emission. The diffuse stellar envelope is similar in size to the clumpy CO molecular gas distribution. The centroid of the stellar envelope is offset by 1 kpc from the unresolved nucleus, suggesting GN20 is involved in an interaction or merger event supported by its location as the brightest galaxy in a proto-cluster. The stellar size of GN20 is larger by a factor of about 3-5 than known spheroids, disks, and irregulars at $z\sim$4, while its size and low S\'ersic index are similar to those measured in dusty, infrared luminous galaxies at $z\sim$2 of the same mass. GN20 has all the ingredients necessary for evolving into a massive spheroidal quiescent galaxy at intermediate $z$: it is a large, luminous galaxy at $z$=4.05 involved in a short and massive starburst centred in the stellar nucleus and extended over the entire galaxy, out to radii of 4 kpc, and likely induced by the interaction or merger with a member of the proto-cluster.Comment: 7 pages, 4 figure

Strong (Hb + [OIII]) and Ha emitters at redshift z ~ 7-8 unveiled with JWST/NIRCam and MIRI imaging in the Hubble eXtreme Deep Field (XDF)

The JWST is revolutionizing the study of high-redshift galaxies by providing for the first time a high-sensitivity view of the early Universe at infrared wavelengths, both with its Near Infrared Camera (NIRCam) and Mid Infrared Instrument (MIRI). In this paper, we make use of medium and broad-band NIRCam imaging, as well as ultra-deep MIRI 5.6 microns imaging, in the Hubble eXtreme Deep Field (XDF) to identify prominent line emitters at z ~ 7-8. Out of a total of 58 galaxies at z ~ 7-8, we find 18 robust candidates (~31%) for prominent (Hb + [OIII]) emitters, based on their enhanced fluxes in the F430M and F444W filters, with rest-frame EW(Hb + [OIII]) ~ 87 - 2100 A. Among these emitters, 16 lie on the MIRI coverage area and 12 show a clear flux excess at 5.6 microns, indicating the simultaneous presence of a prominent Ha emission line with rest-frame EW(Ha) ~ 200 - 3000 A. This is the first time that Ha emission can be detected in individual galaxies at z>7. The Ha line, when present, allows us to separate the contributions of the Hb and [OIII] emission lines to the (Hb + [OIII]) complex and derive Ha-based star formation rates (SFRs). We find that in some cases [OIII]/Hb > 1, suggesting low metallicities, but a few have [OIII]/Hb < 1, so the NIRCam flux excess is mainly driven by Hb. The vast majority of prominent line emitters are very young starbursts or galaxies on their way to/from the starburst cloud. They make for a cosmic SFR density log10(SFRD_Ha / Msun yr^-1 Mpc^-3) ~ 2.35, which is about a third of the total value at z ~ 7-8. Therefore, the strong Ha emitters likely had an important role in reionization.Comment: 15 pages, 9 figures. Submitted to Ap

South-to-north migration preceded the advent of intensive farming in the Maya region

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: The aligned sequences have been deposited in the European Nucleotide Archive database under accession code PRJEB49391. The processed genotype data used in analysis are available online on the Nature Communications website as Supplementary Data 9.The genetic prehistory of human populations in Central America is largely unexplored leaving an important gap in our knowledge of the global expansion of humans. We report genome-wide ancient DNA data for a transect of twenty individuals from two Belize rock-shelters dating between 9,600-3,700 calibrated radiocarbon years before present (cal. BP). The oldest individuals (9,600-7,300 cal. BP) descend from an Early Holocene Native American lineage with only distant relatedness to present-day Mesoamericans, including Mayan-speaking populations. After ~5,600 cal. BP a previously unknown human dispersal from the south made a major demographic impact on the region, contributing more than 50% of the ancestry of all later individuals. This new ancestry derived from a source related to present-day Chibchan speakers living from Costa Rica to Colombia. Its arrival corresponds to the first clear evidence for forest clearing and maize horticulture in what later became the Maya region.Alphawood FoundationNational Science Foundation (NSF)National Institutes of Health (NIH)John Templeton FoundationPaul G. Allen Family Foundatio