The availability of fast alignment-free algorithms has greatly reduced the computational burden of RNA-seq processing, especially for relatively poorly assembled genomes. Using these approaches, ...previous RNA-seq datasets could potentially be processed and integrated with newly sequenced libraries. Confounding factors in such integration include sequencing depth and methods of RNA extraction and selection. Different selection methods (typically, either polyA-selection or rRNA-depletion) omit different RNAs, resulting in different fractions of the transcriptome being sequenced. In particular, rRNA-depleted libraries sample a broader fraction of the transcriptome than polyA-selected libraries. This study aimed to develop a systematic means of accounting for library type that allows data from these two methods to be compared.
The method was developed by comparing two RNA-seq datasets from ovine macrophages, identical except for RNA selection method. Gene-level expression estimates were obtained using a two-part process centred on the high-speed transcript quantification tool Kallisto. Firstly, a set of reference transcripts was defined that constitute a standardised RNA space, with expression from both datasets quantified against it. Secondly, a simple ratio-based correction was applied to the rRNA-depleted estimates. The outcome is an almost perfect correlation between gene expression estimates, independent of library type and across the full range of levels of expression.
A combination of reference transcriptome filtering and a ratio-based correction can create equivalent expression profiles from both polyA-selected and rRNA-depleted libraries. This approach will allow meta-analysis and integration of existing RNA-seq data into transcriptional atlas projects.
We present observational evidence that carbonates and iron-rich clays are present on the surface of Ceres. These components are also present in CI chondrites and provide a means of explaining the ...unusual spectrum of this object as well as providing potential insight into its evolution.
There is a growing trend to treat displaced midshaft clavicular fractures with primary open reduction and plate fixation; whether such treatment results in improved patient outcomes is debatable. The ...aim of this multicenter, single-blinded, randomized controlled trial was to compare union rates, functional outcomes, and economic costs for displaced midshaft clavicular fractures that were treated with either primary open reduction and plate fixation or nonoperative treatment.
In a prospective, multicenter, stratified, randomized controlled trial, 200 patients between sixteen and sixty years of age who had an acute displaced midshaft clavicular fracture were randomized to receive either primary open reduction and plate fixation or nonoperative treatment. Functional assessment was conducted at six weeks, three months, six months, and one year with use of the Disabilities of the Arm, Shoulder and Hand (DASH) and Constant scores. Union was evaluated with use of three-dimensional computed tomography. Complications were recorded, and an economic evaluation was performed.
The rate of nonunion was significantly reduced after open reduction and plate fixation (one nonunion) as compared with nonoperative treatment (sixteen nonunions) (relative risk = 0.07; p = 0.007). Group allocation to nonoperative treatment was independently predictive of the development of nonunion (p = 0.0001). Overall, DASH and Constant scores were significantly better after open reduction and plate fixation than after nonoperative treatment at the time of the one-year follow-up (DASH score, 3.4 versus 6.1 p = 0.04; Constant score, 92.0 versus 87.8 p = 0.01). However, when patients with nonunion were excluded from analysis, there were no significant differences in the Constant scores or DASH scores at any time point. Patients were less dissatisfied with symptoms of shoulder droop, local bump at the fracture site, and shoulder asymmetry in the open reduction and plate fixation group (p < 0.0001). The cost of treatment was significantly greater after open reduction and plate fixation (p < 0.0001).
Open reduction and plate fixation reduces the rate of nonunion after acute displaced midshaft clavicular fracture compared with nonoperative treatment and is associated with better functional outcomes. However, the improved outcomes appear to result from the prevention of nonunion by open reduction and plate fixation. Open reduction and plate fixation is more expensive and is associated with implant-related complications that are not seen in association with nonoperative treatment. The results of the present study do not support routine primary open reduction and plate fixation for the treatment of displaced midshaft clavicular fractures.
Disease stage and recipient/donor human leukocyte antigen (HLA) matching are important determinants of outcome in transplantation using volunteer-unrelated donors (VUD). Matching for HLA-A, -B, -C, ...-DRB1, -DQB1 is beneficial, whereas the importance of DPB1 matching is more controversial. The impact of HLA matching status may differ dependent on disease stage. We investigated the outcome according to the degree of HLA matching at 6 loci, in 488 recipients of predominantly T-cell depleted bone marrow VUD transplants for leukaemia. Survival was significantly better in 12/12-matched transplants in those with early leukaemia (5 years: 63 versus 41% in 10/10 matched, P=0.006), but not late stage disease. Conversely, within the HLA-mismatched group (< or =9/10), there was a significant survival advantage to DPB1 mismatching (5 years: 39 versus 21% in DPB1 matched, P=0.008), particularly in late leukaemia (P=0.01), persisting in multivariate analysis (odds ratio 0.478; 95% confidence interval 0.30, 0.75; P=0.001). These novel findings suggest that the best outcome for patients with early leukaemia, with a 10/10-matched donor, is achieved by matching for DPB1. Conversely, our results suggest that in patients receiving an HLA-mismatched graft, the outcome is significantly better if they are also mismatched for DPB1. We recommend validation of these results in independent datasets.
The near-infrared spectrometer on board the Japanese Hayabusa spacecraft found a variation of more than 10% in albedo and absorption band depth in the surface reflectance of asteroid 25143 Itokawa. ...Spectral shape over the 1-micrometer absorption band indicates that the surface of this body has an olivine-rich mineral assemblage potentially similar to that of LL5 or LL6 chondrites. Diversity in the physical condition of Itokawa's surface appears to be larger than for other S-type asteroids previously explored by spacecraft, such as 433 Eros.
mRNA-like long non-coding RNAs (lncRNAs) are a significant component of mammalian transcriptomes, although most are expressed only at low levels, with high tissue-specificity and/or at specific ...developmental stages. Thus, in many cases lncRNA detection by RNA-sequencing (RNA-seq) is compromised by stochastic sampling. To account for this and create a catalogue of ruminant lncRNAs, we compared de novo assembled lncRNAs derived from large RNA-seq datasets in transcriptional atlas projects for sheep and goats with previous lncRNAs assembled in cattle and human. We then combined the novel lncRNAs with the sheep transcriptional atlas to identify co-regulated sets of protein-coding and non-coding loci.
Few lncRNAs could be reproducibly assembled from a single dataset, even with deep sequencing of the same tissues from multiple animals. Furthermore, there was little sequence overlap between lncRNAs that were assembled from pooled RNA-seq data. We combined positional conservation (synteny) with cross-species mapping of candidate lncRNAs to identify a consensus set of ruminant lncRNAs and then used the RNA-seq data to demonstrate detectable and reproducible expression in each species. In sheep, 20 to 30% of lncRNAs were located close to protein-coding genes with which they are strongly co-expressed, which is consistent with the evolutionary origin of some ncRNAs in enhancer sequences. Nevertheless, most of the lncRNAs are not co-expressed with neighbouring protein-coding genes.
Alongside substantially expanding the ruminant lncRNA repertoire, the outcomes of our analysis demonstrate that stochastic sampling can be partly overcome by combining RNA-seq datasets from related species. This has practical implications for the future discovery of lncRNAs in other species.
Two of the instruments onboard the OSIRIS-REx spacecraft, the MapCam color imager and the OVIRS visible and 20 infrared spectrometer, observed the surface of asteroid (101955) Bennu in partially ...overlapping wavelengths. 21 Significant scientific advances have been enabled by using data from these two instruments in tandem, but a robust 22 statistical understanding of their relationship is needed for future analyses to cross-compare their data as accurately 23 and sensitively as possible. Here we present a cross-instrument comparison of data acquired by MapCam and 24 OVIRS, including methods and results for all global and site-specific observation campaigns in which both 25 instruments were active. In our analysis, we consider both the absolute radiometric offset and the relative 26 (normalized) variation between the two instruments; we find that both depend strongly on the photometric and 27 instrumental conditions during the observation. The two instruments have a large absolute offset (>15%) due to their 28 independent radiometric calibrations. However, they are very consistent (relative offset as low as 1%) when each 29 instrument’s response is normalized at a single wavelength, particularly at low phase angles where shadows on 30 Bennu’s rough surface are minimized. We recommend using the global datasets acquired at 12:30 pm local solar 31 time for cross-comparisons; data acquired at higher phase angles have larger uncertainties.
RAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor gene Apc in the murine intestine. To avoid the impact of direct ...targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets. Deletion of these indicated that while TIAM1 deficiency could suppress Apc-driven hyperproliferation, it had no impact upon tumourigenesis, while VAV3 deficiency had no effect. Intriguingly, deletion of either gene resulted in upregulation of Vav2, with subsequent targeting of all three (Vav2
Vav3
Tiam1
), profoundly suppressing hyperproliferation, tumourigenesis and RAC1 activity, without impacting normal homeostasis. Critically, the observed RAC-GEF dependency was negated by oncogenic KRAS mutation. Together, these data demonstrate that while targeting RAC-GEF molecules may have therapeutic impact at early stages, this benefit may be lost in late stage disease.
Mastitis is the most prevalent disease in dairy sheep with major economic, hygienic and welfare implications. The disease persists in all dairy sheep production systems despite the implementation of ...improved management practises. Selective breeding for enhanced mastitis resistance may provide the means to further control the disease. In the present study, we investigated the genetic architecture of four mastitis traits in dairy sheep. Individual animal records for clinical mastitis occurrence and three mastitis indicator traits (milk somatic cell count, total viable bacterial count in milk and the California mastitis test) were collected monthly throughout lactation for 609 ewes of the Greek Chios breed. All animals were genotyped with a custom-made 960-single nucleotide polymorphism (SNP) DNA array based on markers located in quantitative trait loci (QTL) regions for mastitis resistance previously detected in three other distinct dairy sheep populations.
Heritable variation and strong positive genetic correlations were estimated for clinical mastitis occurrence and the three mastitis indicator traits. SNP markers significantly associated with these mastitis traits were confirmed on chromosomes 2, 3, 5, 16 and 19. We identified pathways, molecular interaction networks and functional gene clusters for mastitis resistance. Candidate genes within the detected regions were identified based upon analysis of an ovine transcriptional atlas and transcriptome data derived from milk somatic cells. Relevant candidate genes implicated in innate immunity included SOCS2, CTLA4, C6, C7, C9, PTGER4, DAB2, CARD6, OSMR, PLXNC1, IDH1, ICOS, FYB, and LYFR.
The results confirmed the presence of animal genetic variability in mastitis resistance and identified genomic regions associated with specific mastitis traits in the Chios sheep. The conserved genetic architecture of mastitis resistance between distinct dairy sheep breeds suggests that across-breed selection programmes would be feasible.
Context. Super-luminous supernovae (SLSNe) are rare events defined as being significantly more luminous than normal terminal stellar explosions. The source of the additional power needed to achieve ...such luminosities is still unclear. Discoveries in the local Universe (i.e. z < 0.1) are scarce, but afford dense multi-wavelength observations. Additional low-redshift objects are therefore extremely valuable. Aims. We present early-time observations of the type I SLSN ASASSN-18km/SN 2018bsz. These data are used to characterise the event and compare to literature SLSNe and spectral models. Host galaxy properties are also analysed. Methods. Optical and near-IR photometry and spectroscopy were analysed. Early-time ATLAS photometry was used to constrain the rising light curve. We identified a number of spectral features in optical-wavelength spectra and track their time evolution. Finally, we used archival host galaxy photometry together with H II region spectra to constrain the host environment. Results. ASASSN-18km/SN 2018bsz is found to be a type I SLSN in a galaxy at a redshift of 0.0267 (111 Mpc), making it the lowest-redshift event discovered to date. Strong C II lines are identified in the spectra. Spectral models produced by exploding a Wolf-Rayet progenitor and injecting a magnetar power source are shown to be qualitatively similar to ASASSN-18km/SN 2018bsz, contrary to most SLSNe-I that display weak or non-existent C II lines. ASASSN-18km/SN 2018bsz displays a long, slowly rising, red “plateau” of >26 days, before a steeper, faster rise to maximum. The host has an absolute magnitude of –19.8 mag (r), a mass of M⋆ = 1.5−0.33+0.08 × 109 M⊙ M ⋆ = 1.5 − 0.33 + 0.08 × 10 9 M ⊙ $ M_\star=1.5_{-0.33}^{+0.08}\times10^9M_\odot $ , and a star formation rate of = 0.50−0.19+2.22 M⊙ yr −1 = 0.50 − 0.19 + 2.22 M ⊙ yr − 1 $ =0.50_{-0.19}^{+2.22}M_\odot\text{yr}^{-1} $ . A nearby H II region has an oxygen abundance (O3N2) of 8.31 ± 0.01 dex.
PDF
