Miracle-dz/UniFAR-FTUs huggingface dataset:
Ultra-fast Identity by Descent Detection in Biobank-Scale Cohorts using Positional Burrows–Wheeler Transform

With the availability of genotyping data of very large samples, there is an increasing need for tools that can efficiently identify genetic relationships among all individuals in the sample. One fundamental measure of genetic relationship of a pair of individuals is identity by descent (IBD), chromosomal segments that are shared among two individuals due to common ancestry. However, the efficient identification of IBD segments among a large number of genotyped individuals is a challenging computational problem. Most existing methods are not feasible for even thousands of individuals because they are based on pairwise comparisons of all individuals and thus scale up quadratically with sample size. Some methods, such as GERMLINE, use fast dictionary lookup of short seed sequence matches to achieve a near-linear time efficiency. However, the number of short seed matches often scales up super-linearly in real population data. In this paper we describe a new approach for IBD detection. We take advantage of an efficient population genotype index, Positional BWT (PBWT), by Richard Durbin. PBWT achieves linear time query of perfectly identical subsequences among all samples. However, the original PBWT is not tolerant to genotyping errors which often interrupt long IBD segments into short fragments. We introduce a randomized strategy by running PBWTs over random projections of the original sequences. To boost the detection power we run PBWT multiple times and merge the identified IBD segments through interval tree algorithms. Given a target IBD segment length, RaPID adjust parameters to optimize detection power and accuracy. Simulation results proved that our tool (RaPID) achieves almost linear scaling up to sample size and is orders of magnitude faster than GERMLINE. At the same time, RaPID maintains a detection power and accuracy comparable to existing mainstream algorithms, GERMLINE and IBDseq. Running multiple times with various target detection lengths over the 1000 Genomes Project data, RaPID can detect population events at different time scales. With our tool, it is feasible to identify IBDs among hundreds of thousands to millions of individuals, a sample size that will become reality in a few years.
Rh glycoprotein immunoreactivity in the skin and its role in extrabranchial ammonia excretion by the sea lamprey (Petromyzon marinus) in fresh water

Aquatic organisms employ various strategies to excrete ammonia across the gills, skin, and (or) renal routes. During three different stages of their life cycle, we hypothesized that the basal vertebrate sea lamprey (Petromyzon marinus L., 1758) used the skin as a route for ammonia excretion. Measurements of ammonia excretion using divided flux chambers revealed that extrabranchial sites (skin plus renal) of ammonia excretion were quantitatively more important in larval sea lampreys, but following metamorphosis, the gills became the dominant route of excretion in juvenile sea lampreys. Despite the greater relative importance of the skin in the larval stage, Rh glycoprotein isoforms Rhbg, Rhcg1, and Rhcg2 were detected in the skin in all three sea lamprey life stages examined, but the patterns of expression were dependent on the life stage. We conclude that, during the relatively sedentary filter-feeding larval stage, extrabranchial routes play an equally important role as the gill in facilitating ammonia e.
Distribution, body size, genetic structure and conservation of Siphlaenigma janae (Insecta: Ephemeroptera)

ABSTRACT Distribution, body size and genetic structure of the poorly known New Zealand mayfly Siphlaenigma janae were investigated to improve understanding of its conservation status. It has now been recorded from 42 locations, 22 of which are reported for the first time. The distribution of S. janae extends from Northland to the central North Island, and also into the northwestern South Island. Population structure consisted of three distinct haplotype networks; two in the North Island and one in the South Island. Maximum uncorrected genetic distance was 6.1% but no strong evidence for the presence of sibling species was found. The specialist nymphs predominantly live in low-gradient first- and second-order forested streams, a habitat that is increasingly being threatened by land-use modification. We recommend S. janae remain classified as Nationally Vulnerable due to its unique taxonomic position, regionally distinct genetic structure and fragmented population that is likely experiencing ongoing decline.
Nest Height and Vertical Vegetation Associated with Black-capped Vireo Breeding Success in Southwest Texas

Abstract Vireo atricapilla (Black-capped Vireo) is an endangered songbird whose habitat use has been well studied in central portions of its breeding range, which is characterized by successional vegetation communities. To expand our understanding of habitat use as it relates to reproductive success, we studied Black-capped Vireo habitat use at the territory and nest-site scales in southwest Texas in 2009 and 2010, an area characterized by xeric and stable vegetation communities. We measured vegetation in territories and at nests to evaluate the influence of habitat variables on nest parasitism and nest survival. Our results showed that Black-capped Vireo nest-site use in southwest Texas differed from that in breeding areas of central Texas and Oklahoma. Black-capped Vireos in southwest Texas used nest sites with a wide range of woody cover (70 ± 13%) and used Juniperus spp. (junipers) as a nest substrate proportionately more than its availability in territories, which is contradictory to previously published literature. Nest parasitism increased significantly with greater nest height, likely due to increased visibility to Molothrus ater (Brown-headed Cowbird). Increasing height of vertical cover above the nest was associated with decreased overall nest survival, likely because nests placed in habitat with taller vegetation are more susceptible to avian predators and Brown-headed Cowbird parasitism. Unlike the findings of studies conducted in the northern part of the species' breeding range, we found that parasitism did not increase the likelihood of depredation or abandonment. Our results indicate that Black-capped Vireo habitat structure and composition, as well as factors influencing nest success in Southwest Texas, differ from their breeding habitat in central Texas and Oklahoma, indicating that management guidelines need to be regi on-specific.
The Role of LXR in Glucocorticoid-Induced Osteoporosis and Muscle Wasting

Synthetic glucocorticoids (GCs) have unparalleled anti-inflammatory and immunosuppressive properties that are crucial for the treatment of many inflammatory diseases. Unfortunately, a remaining limitation for the long-term therapeutic use of GCs is the development of major metabolic side effects, including Cushing’s syndrome, a disease characterized by metabolic dysregulations such as hyperglycemia, muscle wasting and osteoporosis. The glucocorticoid receptor (GR) and liver X receptor (LXR) are members of the nuclear receptor superfamily that regulate distinct but overlapping transcriptional programs. Using a Cushing’s mouse model of GC excess, as well as in vitro cell lines treated with synthetic GCs, we find that LXR antagonism is protective from GC-induced osteoclast activation, but not from the anti-osteoblastogenic or muscle atrophy effect of GCs; suggesting a cell type specific effect. Together, these studies show the selective regulation of LXR antagonism may be useful in preventing GC-induced osteoclast activation.
Anti-obesity and haematological effects of Malaysia Hibiscus sabdariffa L. aqueous extract on obese Sprague Dawley rats

Background: Hibiscus sabdariffa L. (Hs; Malvaceae) is commonly known as roselle or red sorrel in English or karkadè in Arabic. It is a tropical plant native to India and Malaysia. Roselle extracts have been widely reported to have beneficial health effects. The aim of this study was to determine the effective dose of Hs aqueous extract, which is a possible reducing agent in diet-induced obese rats, and monitoring any toxicological effect.Methods: Male Sprague Dawley rats (n= 24) aged 6-7 weeks and weighing 210 ± 3.5 g (mean ± S.E.M) were used. The rats were fed a high fat diet (HFD) for 8 consecutive weeks to induce obesity. The animals were then randomly assigned to one of five groups based on the concentration of Hs aqueous extract. The normal group (NG) received a normal diet (commercial chow) throughout the study. The obese group (ObG) included obese rats administered with tap water ad libitum. Groups 1 (150 mg/kg), 2 (200 mg/kg), 3 (250 mg/kg), and 4 (300 mg/kg) were obese rats continuously fed with HFD in combination with the Hs extract for 10 weeks. The effect of Hs on some haematological and blood biochemical parameters were also evaluated.Results: Hs aqueous extract is a rich source of anthocyanins. The main compounds detected are delphinidin-3-O-sambubioside and delphinidin-3-O-sambubioside. The extract also possesses high antioxidant properties which may be caused by these anthocyanins. The anti-obesity effect of Hs aqueous extract was demonstrated by the significant reduction in the weight gain and abdominal weight (p < 0.05) between treated and non-treated groups, which was dose-dependent. Overall, our study demonstrated that oral administration of Hs at doses of 150, 200, 250, and 300 mg/kg for ten weeks did not cause any toxicity effect within the obese rats.Conclusions: The results of the study implied Hs aqueous extract at 300 mg/kg is the dose which can the most weight reduction effect with no severe haematological and biochemical changes in all experimental animals.Keywords: Hibiscus sabdariffa, obese rats, roselle, aqueous extract, and body weight
Effects of management and natural disturbance on oribatid mites in montane forest

The thesis studied effects of forest management and natural disturbance on oribatid mites in montane forests in South Bohemia (Czech Republic). We focused on the influence of (1) spruce monoculture establishment on the former beech forest, (2) management intensification in spruce forest and (3) forest dieback after bark-beetle outbreak. The impacts were pronounced especially like changes in species composition and distribution of functional traits.
The Persistence of Molecular Vibration in Collisions

The dispersion of sound is theoretically interpreted by the idea that the exchange of energy in collisions between molecular translation and rotation on one side and vibration on the other side is much slower than, for example, between the various translational degrees of freedom. It seemed desirable to find a direct optical method of observing this hypothetical effect. Apparatus has been developed in this laboratory for the purpose of investigating molecules present in very small concentration, like radicals, by their absorption spectra; with this method, relative concentrations of molecules are determined by comparing intensities of certain rotational lines. This test was applied to the higher vibrational levels of the I2 molecule. Their concentration was artificially increased beyond the small amount present in thermal equilibrium by an electric discharge of brief duration. By varying the phase between an electric switch and optical shutter, snapshots of the absorption spectrum could be taken at differ.
Isolation and sequencing of AGO-bound RNAs reveals characteristics of mammalian stem-loop processing in vivo

MicroRNA precursors (pre-miRNAs) are short hairpin RNAs that are rapidly processed into mature microRNAs (miRNAs) in the cytoplasm. Due to their low abundance in cells, sequencing-based studies of pre-miRNAs have been limited. We successfully enriched for and deep sequenced pre-miRNAs in human cells by capturing these RNAs during their interaction with Argonaute (AGO) proteins. Using this approach, we detected > 350 pre-miRNAs in human cells and > 250 pre-miRNAs in a reanalysis of a similar study in mouse cells. We uncovered widespread trimming and non-templated additions to the 3’ ends of pre- and mature miRNAs. Additionally, we created an index for microRNA precursor processing efficiency. This analysis revealed a subset of pre-miRNAs that produce low levels of mature miRNAs despite abundant precursors, including an annotated miRNA in the 5’ UTR of the DiGeorge syndrome critical region 8 mRNA transcript. This led us to search for AGO-associated stem-loops originating from other mRNA species, which identified hundreds of putative pre-miRNAs derived from human and mouse mRNAs. In summary, we provide a wealth of information on mammalian pre-miRNAs, and identify novel microRNA and microRNA-like elements localized in mRNAs.
Investigation of resolvin E1 as a metabolite of eicosapentaenoic acid with anti-colorectal cancer activity

Eicosapentaenoic acid (EPA) is an omega (ω)-3 polyunsaturated fatty acid (PUFA) found at high levels in oily fish such as salmon and mackerel. EPA has been shown to have anti-colorectal cancer (CRC) effects in two clinical studies where it was shown to reduce polyp burden in familial adenomatous polyposis (FAP) patients, and possibly improve overall survival in patients following liver resection for CRC liver metastases. At present, it is unknown how EPA exerts its anti-CRC effects. Resolvin E1 (RvE1) is a lipid with anti-inflammatory and pro-resolving activities derived from EPA. RvE1 biosynthesis requires three enzymes; aspirin acetylated cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and leukotriene A4 hydrolase (LTA4H). RvE1 has been shown to mediate its anti-inflammatory effects through two different G-protein coupled receptors, ChemR23 and BLT1. The hypothesis was that RvE1 synthesised within CRC could induce CRC cell apoptosis through either or both ChemR23 and BLT1 receptor signaling. ChemR23 and BLT1 protein were found to be expressed by human CRC clinical samples. ChemR23 and BLT1 were expressed at lower levels in histologically normal colorectal epithelium when compared to CRC, a relationship also seen with the associated stroma. No RvE1 mediated effect on CRC survival or apoptosis was identified on ChemR23 expressing human CRC cell lines in vitro. There was no BLT1 expression by human CRC cells in vitro. Human polymorphonuclear leukocytes (PMNs) treated directly with 18- hydroxyeicosapentaenoic acid (18-HEPE) generated RvE1. In vitro CRC cells and macrophages alone and in a transcellular synthesis model failed to produce RvE1. In conclusion, ChemR23 and BLT1 receptors were found to be expressed by human CRC clinical samples. RvE1 was not synthesised by a CRC model in vitro. The candidate identified no in vitro RvE1 biological activity. Further research could look to establish whether RvE1 can be detected in human CRC samples.
An mRNA-reprogramming method with improved kinetics and efficiency and the successful transdifferentiation of human fibroblasts using modified mRNA

Induced pluripotent stem (iPS) cells have the potential to generate a wide array of cell types from multiple lineages that enable us to explore the mechanisms that are involved in the conversion of cell states. The reprogramming process that generates iPS cells is complex, but since its discovery, technical advancements and improvements in the methodology have improved the speed and efficiency of generating integration-free, clinically relevant iPS cells. However, despite improvements, the mechanisms of reprogramming are not fully understood and so the process remains largely inefficient and slow. It has been reported that reprogramming mediated through the delivery of exogenous mRNAs encoding OCT4, SOX2, KLF4 and cMYC is a fast and efficient method for generating integration-free iPS cells. Here we show that mRNA reprogramming can be enhanced further by employing an mRNA dose-ramping approach that provides greater control of the dose of mRNA that is introduced into the target cells. This improvement upon existing methods promotes the viability of the target cells during reprogramming which in turn improves the efficiency, speed and success of generating iPS cells. We also show that an optimisation to the reprogramming factor cocktail, replacing OCT4 with a fusion between OCT4 and the transcriptional activation domain of MYOD1 – called M3O, further improves the kinetics of reprogramming. Reprogramming disease cells is also possible in that several iPS cell-disease models have been established that have successfully modelled aspects of disease development in vitro. Here we show the applicability of using the mRNA approach we have developed, on neuroblastoma cells and the characterisation of iPS cells reprogrammed from neuroblastoma cells using OCT4, SOX2, KLF4 and cMYC delivered using Sendai viral vectors. Finally, we demonstrate how human fibroblasts introduced to a vector encoding MYOD1 causes them to transdifferentiate in to myoblast-like cells without a genomic footprint. Together this data demonstrates how integration-free mRNA can be used to control gene expression to direct cell fate through reprogramming and transdifferentiation. This mRNA approach provides proof of concept that warrants the testing of other genes to explore their function in reprogramming and other pathways that govern cell fate.
The composition and richness of the land-snail fauna of gallery forest along the Muvumba River in Rwanda

We investigated the land-snail fauna in gallery forest sites along a 30-km long section of the Muvumba River in northeastern Rwanda. A total of 12,419 individuals assigned to 34 land-snail species were collected in 24 plots. Though the number of species is small compared with protected rainforests in the northern Albertine Rift, gallery forests are important as corridors for colonization for the forest fauna. Despite a strong human impact on the gallery forests, hardly any obviously introduced species were recorded. The composition of the snail assemblages was significantly affected by elevation, depth of leaf litter and the presence of dead wood. The high median abundances of the snails in the gallery forests, which are among the highest recorded from forests in the northern Albertine Rift, are probably the result of a higher average soil calcium content in these gallery forests, caused by flooding. The significant increase of land-snail species richness with elevation might be the result of a higher input of calcium into the upper part of the study area.
A zebrafish model of developmental joint dysplasia: Manipulating the larval mechanical environment to drive the malformation and recovery of joint shape

Developmental dysplasia of the hip (DDH), a malformation of the acetabulum, is a frequent cause of early onset osteoarthritis. The disease encompasses a spectrum of severities, some of which are more amenable to treatment. Embryonic immobilisation significantly impairs the development of joint shape however the impact of this malformation to the function and growth of the joint in the short to medium term is unclear. We developed a novel model of developmental joint dysplasia using the zebrafish jaw joint to identify the mechanisms regulating cellular plasticity and ability to recover joint shape and function. Larval zebrafish were immobilised either pharmacologically or using targeted ablation of jaw muscles to induce an altered joint shape. Following restoration of muscle activity we dynamically monitored the joint shape and function in individuals at cellular resolution impossible in other vertebrate species. Reflecting the variability of the human condition we found a proportion of joints will recover both their shape and function, while others will not; despite coming from a genetically homogenous population. This allowed us to study what controls likelihood of recovery; we identified a number of cellular changes that predict likelihood of functional recovery, including position of precursor cells, and specific patterns of proliferation, migration and differentiation in joints and associated connective tissues. These factors together predict recovery better than severity of malformation alone. Using Finite Element Analysis we studied the mechanics of joints representative of ones that recover and those that fail to identify differences in patterns of strain that could explain the cellular behaviours that underpin likelihood of recovery. Thus, this model would enable the study of the short to long term impact of altered joint shape on function and could help to identify the changes that render an individual more receptive to treatment and therefore may potentially be indicative of long term joint health.
Screening of Epiphytic Isolates from Different Crops for Plant Growth Promoting Traits

Microorganisms are present in soil, near and above the roots and also present on aerial part of plants like leaves. Ruinen (1961) introduced term phyllosphere for plant leaf surface. The termed epiphytes used for inhabitants of phyllosphere. The diverse range of bacteria, filamentous fungi, yeasts and algae which are important for plant health and growth are present on phyllosphere (Whipps et al., 2008; Vorholt, 2012). The total count of microbes approximately is about 6.4 x 10 8 km 2
Double-Linear Thompson Sampling for Context-Attentive Bandits

In this paper, we analyze and extend an online learning frame-work known as Context-Attentive Bandit, motivated by various practical applications, from medical diagnosis to dialog systems, where due to observation costs only a small subset of a potentially large number of context variables can be observed at each iteration; however, the agent has a freedom to choose which variables to observe. We derive a novel algorithm, called Context-Attentive Thompson Sampling (CATS), which builds upon the Linear Thompson Sampling approach, adapting it to Context-Attentive Bandit setting. We provide a theoretical regret analysis and an extensive empirical evaluation demonstrating advantages of the proposed approach over several baseline methods on a variety of real-life datasets.
DBA bandits: Self-driving index tuning under ad-hoc, analytical workloads with safety guarantees

Automating physical database design has remained a long-term interest in database research due to substantial performance gains afforded by optimised structures. Despite significant progress, a majority of today’s commercial solutions are highly manual, requiring offline invocation by database administrators (DBAs) who are expected to identify and supply representative training workloads. Even the latest advancements like query stores provide only limited support for dynamic environments. This status quo is untenable: identifying representative static workloads is no longer realistic; and physical design tools remain susceptible to the query optimiser’s cost misestimates.We propose a self-driving approach to online index selection that eschews the DBA and query optimiser, and instead learns the benefits of viable structures through strategic exploration and direct performance observation. We view the problem as one of sequential decision making under uncertainty, specifically within the bandit learning setting. Multi-armed bandits balance exploration and exploitation to provably guarantee average performance that converges to policies that are optimal with perfect hindsight. Our simplified bandit framework outperforms deep reinforcement learning (RL) in terms of convergence speed and performance volatility. Comprehensive empirical results demonstrate up to 75% speed-up on shifting and ad-hoc workloads and 28% speed-up on static workloads compared against a state-of-the-art commercial tuning tool and up to 58% speed-up against the deep RL alternatives.