Miracle-dz/UniFAR-FTUs huggingface dataset:
Defining data-driven primary transcript annotations with primaryTranscriptAnnotation in R

Nascent transcript measurements derived from run-on sequencing experiments are critical for the investigation of transcriptional mechanisms and regulatory networks. However, conventional gene annotations specify the boundaries of mRNAs, which significantly differ from the boundaries of primary transcripts. Moreover, transcript isoforms with distinct transcription start and end coordinates can vary between cell types. Therefore, new primary transcript annotations are needed to accurately interpret run-on data. We developed the primaryTranscriptAnnotation R package to infer the transcriptional start and termination sites of annotated genes from genomic run-on data. We then used these inferred co-ordinates to annotate transcriptional units identified de novo. Hence, this package provides the novel utility to integrate data-driven primary transcript annotations with transcriptional unit coordinates identified in an unbiased manner. Our analyses demonstrated that this new methodology increases the sensitivity for detecting differentially expressed transcripts and provides more accurate quantification of RNA polymerase pause indices, consistent with the importance of using accurate primary transcript coordinates for interpreting genomic nascent transcription data. Availability https://github.com/WarrenDavidAnderson/genomicsRpackage/tree/master/primaryTranscriptAnnotation
Function prediction of transcription start site associated RNAs (TSSaRNAs) in Halobacterium salinarum NRC-1

xv Resumo . xviii
Seeing β-arrestin in action: The role of β-arrestins in Histamine 1 Receptor signaling

ß-arrestins regulate G protein-coupled receptor functions by influencing their signaling activity and intracellular location. Histamine is a major chemical mediator of allergic reactions, and its action is mainly mediated by the Gq/11- and Gi-coupled H1R. Contrary to accumulating insights into G protein-mediated signaling downstream of H1R, very little is known about the function of ß-arrestins in H1R signaling. Here, we describe dynamic, live cell measurements of ß-arrestin recruitment upon H1R activation in HEK293TN cells. Our observations classify H1R as a class A receptor, undergoing transient interactions with ß-arrestin. To investigate the relative contributions of G proteins and ß-arrestins to H1R signaling, we use specific G protein inhibitors, as well as ß-arrestin overexpression and depletion, and quantify various signaling outcomes in a panel of dynamic, live cell biosensor assays. Overall, we link ß-arrestins to desensitization of H1R-mediated signaling and show that ERK activation downstream of endogenous (HeLa, HUVEC) or transiently expressed (HEK293TN) H1R is largely Gq-mediated.
Nutrient dynamics in submarine groundwater discharge through a coral reef (western Lombok, Indonesia)

Submarine groundwater discharge (SGD) from tropical volcanic islands locally transports significant amounts of terrestrial nutrients into the coastal ocean, which can affect sensitive coastal ecosystems such as coral reefs. In northwestern Lombok, terrestrial submarine groundwater discharges through several submarine springs at the seafloor into a coral reef. In order to understand the transport mechanisms of nutrients from land into the reef, we investigated nutrient fluxes via SGD within the area using a combination of different methods, including recharge estimates in the coastal catchment area, echosounder profiling of the seafloor, discharge measurements, and hydrochemical analyses (stable isotopes of water, radon, and nutrients). Different types of springs can be distinguished based on their morphology. One spring showed a “crater”‐shaped structure while other springs consisted of fissures. Recharge rates in the coastal catchment amounted to 5 L s−1, while discharge rates from the largest spring were 5 L s−1 for total SGD and 2.5 L s−1 for fresh SGD, which is similar to discharge rates from smaller onshore springs at the slopes of a volcano. SGD was in general a source of nutrients such as dissolved silicon (~ 226 mol d−1), phosphate (0.61 mol d−1), or total dissolved nitrogen (13.4 mol d−1). Nitrate concentrations varied among the different springs, probably due to different sources in the hinterland, transformations (e.g., denitrification), or biological uptake during transport from land into the ocean. As nitrate can considerably affect coral reef health, our findings suggest that especially nitrate should be monitored around submarine springs in Indonesia.
Cell-wall structure and composition of Penicillium janczewskii as affected by inulin

Penicillium janczewskii, a filamentous fungus isolated from the rhizosphere of Vernonia herbacea (Asteraceae), grows rapidly on media containing either sucrose or inulin as carbon sources. Maintenance of P. janczewskii on inulin medium induces secretion of proteins with high inulinase activity but results in a mycelium that easily collapses and breaks. We evaluated the influence of inulin on fungal growth and colony morphology and on cell-wall structure and composition in comparison with growth and wall characteristics on sucrose-containing medium. P. janczewskii grown on Czapek medium with agar containing 1% (w/v) sucrose or inulin showed differences in the color and morphology of the colonies, although growth rates were similar on both carbon sources. Scanning-electron microscopy revealed that the hyphae from fungus grown on inulin-containing medium are much thinner than those from fungus cultivated on sucrose. Ultrastructural analysis of 5 d old cultures using transmission-electron microscopy indicated significant differences in the cell-wall thickness between hyphae grown on inulin or sucrose media. No differences were detected in the overall carbohydrate and protein contents of cell walls isolated from cultures grown on the two carbon sources. Glycosyl composition analyses showed glucose and galactose as the predominant neutral monosaccharides in the walls but showed no differences attributable to the carbon source. Glycosyl linkage composition analyses indicated a predominance of 3-linked glucopyranosyl in the hyphal walls when P. janczewskii was grown on inulin-containing medium. Our results suggest that growth on inulin as the sole carbon source results in structural changes in the mycelia of P. janczewskii that lead to mycelial walls with altered physical and biological properties.
Invariant chain regulates endosomal fusion and maturation through the SNARE Vti1b

Invariant chain (Ii) is an important multifunctional player in the regulation of adaptive immune responses and is responsible for several cellular functions related to MHCI and MHCII antigen loading and antigen presentation. While regulating endosomal trafficking of MHCII and other proteins that bind to Ii, this molecule is able to influence the endosomal pathway delaying the maturation of endosomes to the late endosomal loading compartments. When expressed in cells Ii is found to increase endosomal size, but the mechanisms for this is not known. We used RNAi silencing to identify SNARE proteins controlling Ii induced increase of endosomal size and delay of the endosomal pathway. Ii was found to interact with the SNARE protein Vti1b. Vti1b localized at the contact sites of fusing Ii positive endosomes and a tailless Ii was able to relocate Vti1b to the plasma membrane. Furthermore, silencing Vti1b, abrogated the delay in endosomal maturation induced by Ii expression. In conclusion, Ii interacts with Vti1b and this interaction is fundamental for Ii-mediated alteration of the endosomal pathway. We propose that Ii, by interacting with SNAREs, in particular Vti1B in the biosynthetic pathway of antigen presenting cells, is able to assemble SNARE directed fusion partners in the early part of the endosomal pathway that lead to a slower endosomal maturation for efficient antigen processing and antigen loading.
Using multiple infection history to infer contact network structure

The structure of host interactions within a population shapes the spread of infectious diseases but contact patterns between hosts are difficult to access. We hypothesised that key properties of these patterns can be inferred by using multiple infections data from individual longitudinal follow-ups. To show this, we simulated multiple infections on a contact network in an unbiased way by implementing a non-Markovian extension of the Gillespie algorithm for a community of parasites spreading on this network. We then analysed the resulting individual infection time series in an original way by introducing the concept of ‘infection barcodes’ to represent the infection history in each host. We find that, depending on infection multiplicity and immunity assumptions, knowledge about the barcode topology makes it possible to recover key properties of the network topology and even of individual nodes. The combination of individual-based simulations and barcode analysis of infection histories opens promising perspectives for the study of infectious disease transmission networks. Significance Statement The way hosts interact with each other is known to shape epidemics spread. However, these interactions are difficult to infer, especially in human populations. Using recent developments in stochastic epidemiological modeling and barcode theory, we show that the diversity of infections each host has undergone over time contains key information about contact network between hosts. This means that longitudinal follow-ups of some individuals in a population can tell us how hosts are in contact with each other. It can also inform us on how connected a particular individual is. This opens new possibilities regarding the use of genetic diversity of infectious diseases in epidemiology.
Prediction of energy load profiles

Prediction of energy load profiles is an important topic in Smart Grid technologies. Accurate forecasts can lead to reduced costs and decreased dependency on commercial power suppliers by adapting to prices on energy market, efficient utilisation of solar and wind energy and sophisticated load scheduling. This thesis compares various statistical and machine learning models and their ability to forecast load profile for an entire day divided into 48 half-hour intervals. Additionally, we examine various preprocessing methods and their influence on the accuracy of the models. We also compare a variety of imputation methods that are designed to reconstruct missing observation commonly present in energy consumption data.
Investigation of the role of VHL-HIF signaling in DNA repair and apoptosis in zebrafish

pVHL is a tumor suppressor. The lack of its function leads to various tumors, among which ccRCC (clear cell renal cell carcinoma) has the most serious outcome due to its resistance to chemotherapies and radiotherapies. Although HIF promotes the progression of ccRCC, the precise mechanism by which the loss of VHL leads to tumor initiation remains unclear. We exploited two zebrafish vhl mutants, vhl and vll, and Tg (phd3:: EGFP)i144 fish to identify crucial functions of Vhl in tumor initiation. Through the mutant analysis, we found that the role of pVHL in DNA repair is conserved in zebrafish Vll. Interestingly, we also discovered that Hif activation strongly suppressed genotoxic stress induced DNA repair defects and apoptosis in vll and brca2 mutants and in embryos lacking ATM activity. These results suggest the potential of HIF as a clinical modulator that can protect cells from accumulating DNA damage and apoptosis which can lead to cancers and neurodegenerative disorders.
Complete mitochondrial genome sequence of the broad-winged damselfly, Mnais pruinosa Selys, 1853 (Odonata: Calopterygidae)

Abstract In this study, we analyzed the complete mitochondrial genome of the Mnais pruinosa Selys, 1853 from Saga Prefecture, Japan. The mitochondrial genome of M. pruinosa was identified as a circular molecule of 15,494 bp, and was found to be similar to that of other damselfly species. It was predicted to contain 13 protein-coding (PCG), 22 tRNA, and two rRNA genes, as well as one A + T-rich control region. The genes ATP8 and ATP6 shared seven nucleotides, ATP6 and COIII shared one nucleotide, ND4 and ND4L shared seven nucleotides, and ND6 and Cytb shared one nucleotide. The initiation codon ATG was found in eight genes, ATC in four, and ATT in one; the termination codons TAA, TAG, incomplete TA, and single T were observed in seven, one, two, and three genes, respectively. All the tRNA genes possessed a cloverleaf secondary structure, except for tRNA-His that lacks the TΨC loop. The average AT content of mitochondrial genome was 66.18%.
First 3D reconstruction and volumetric body mass estimate of the tapinocephalid dinocephalian Tapinocaninus pamelae (Synapsida: Therapsida)

ABSTRACT Dinocephalians were the earliest large terrestrial tetrapods from Gondwana, making this group crucial in understanding body mass (BM) evolution in basal synapsids, but no detailed weight determinations are available for the clade. Here we present the first BM estimate for a dinocephalian on the basis of the remarkably well preserved and complete skeleton of the basal tapinocephalid Tapinocaninus pamelae from the lowermost Beaufort Group of South Africa. We reconstructed three 3D models of Tapinocaninus using mounted skeletons of the dinocephalians Moschops and Ulemosaurus to reconstruct the missing elements. Applying a density range between 0.9 and 1.15 Kg/1000 cm3 for living tissue to the model we reconstructed an average BM of 892.63 Kg for the taxon. Classic regression formulae, based on humerus and femur circumference, provide higher values of 1694.5 Kg and 2015.8 Kg, with an overestimation of 90% and 126% respectively. The study confirms that volumetric BM estimates are more precise, and are recommended if relatively complete skeletons are available. The ‘intermediate’ posture recognized for Tapinocaninus, more upright with respect to the sprawling condition characterizing sphenacodontid ‘pelycosaurs’, could represent a response to a large BM, which, for the first time in synapsids, reaches weights close to a tonne.
Extended correlated principal component analysis with SVM-PUK in opinion mining

With the rapid growth of microblogs and online sites, an inordinate number of product reviews are available on the Internet. They not only help in analyzing, but also assist in making informed decisions about product quality. In the proposed work, an extended correlated principal component analysis (ECPCA) is used for dimensionality reduction. A comparative analysis is conducted on movie reviews (DB-1) and Twitter datasets (DB-2 and DB-3) in opinion mining extraction. The performance of naïve Bayes, CHIRP, and support vector machine (SVM) with kernel methods such as radial basis function (RBF), polynomial, and Pearson (PUK) are compared and analyzed on the three datasets. The experimental results using ECPCA for selecting relevant features and SVM-PUK as a classifier exhibit better performance on movie reviews and Twitter datasets. The performance of the proposed approach is 99.69%, 99.4%, and 99.54% on the DB-1, DB-2, and DB-3 datasets, respectively, and comparatively outperforms the existing methods.
A comparison of complete mitochondrial DNA sequences of Mnais costalis Selys, 1869 (Odonata: Calopterygidae) from three different populations (one allopatric and two sympatric)

Abstract In Japan, two closely-related damselflies, Mnais costalis Selys, 1869 (Odonata: Calopterygidae) and M. pruinosa Selys-Longchamps (Odonata: Calopterygidae), 1853, coexist, and they exhibit geographic variations in wing color, body size, and habitat preference. In this study, we analyzed the complete mitochondrial genome of M. costalis from Saga Prefecture, Japan (sympatric populations that exhibit wing color polymorphism), and compared the genome with M. costalis that exhibit monomorphic orange wing color. The mitochondrial genome of M. costalis from Saga Prefecture was identified as a circular molecule of 15,488 bp, similar to that found in other M. costalis populations. It was predicted to contain 13 protein-coding (PCG), 22 tRNA, and two rRNA genes, along with one A + T-rich control region. Among the PCGs, ATP8 and ATP6, ATP6 and COIII, ND4 and ND4L, and ND6 and Cytb shared seven, one, seven, and one nucleotides, respectively. The initiation codon ATG was found in eight genes, ATC in four, and ATT in one, while the termination codons TAA, TAG, TA, and T were observed in seven, one, two, and three genes, respectively. All the tRNA genes possessed a cloverleaf secondary structure, except for tRNA-His that lacks the TΨC loop. The average AT content of mitochondrial genome was 66.06%. From a phylogenetic analysis, the loss of wing color polymorphism in monomorphic sympatric populations is likely to occur with the coexistence of two Mnais species.
Inhibition of the Myocardin-Related Transcription Factor Pathway Increases Efficacy of Trametinib in NRAS-Mutant Melanoma Cell Lines

The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma; it is aberrantly activated in almost 80% of human cutaneous melanomas (∼50% BRAFV600 mutations and ∼30% NRAS mutations). While targeted therapies have yielded success in BRAFV600 mutant melanoma patients, such therapies have been ineffective in NRAS mutant melanomas in part due to their cytostatic effects and primary resistance in this patient population. Here, we demonstrate that increased Rho/MRTF-pathway activation correlates with high intrinsic resistance to the MEK inhibitor, trametinib, in a panel of NRAS mutant melanoma cell lines. Combination of trametinib with the Rho/MRTF-pathway inhibitor, CCG-222740, synergistically reduced cell viability in NRAS mutant melanoma cell lines in vitro. Furthermore, the combination of CCG-222740 with trametinib induced apoptosis and reduced clonogenicity in SK-Mel-147 cells which have a high level of trametinib resistance. These findings suggest a role of the Rho/MRTF-pathway in intrinsic trametinib resistance in a subset of NRAS mutant melanoma cell lines and highlights the potential of concurrently targeting the Rho/MRTF-pathway and MEK in NRAS mutant melanomas.
Invasion implies substitution in ecological communities with class-structured populations

Long-term evolution of quantitative traits is classically and usefully described as the directional change in phenotype due to the recurrent fixation of new mutations. A formal justification for such continual evolution ultimately relies on the “invasion implies substitution” principle. This states that whenever a mutant allele causing a small phenotypic change can successfully invade a population, the ancestral (or wild-type) allele will be replaced, whereby fostering gradual phenotypic change if the process is repeated. It has been argued that this principle holds in a broad range of situations, including spatially and demographically structured populations experiencing frequency and density dependent selection under demographic and environmental fluctuations. However, prior studies have not been able to account for all aspects of population structure, leaving it unsettled in precisely which models does the “invasion implies substitution”-principle really hold. In this paper, we start by laying out a program to explore and clarify the generality of the “invasion implies substitution”-principle. Particular focus is given on finding an explicit and functionally constant representation of the selection gradient on a quantitative trait. We then show that the “invasion implies substitution”-principle generalizes to well-mixed and scalar-valued polymorphic multispecies ecological communities that are structured into finitely many demographic (or physiological) classes. We do this by setting up a continuous-time mutant-resident dynamical system for several interacting populations and species, and derive a closed expression for the selection gradient by separating the population dynamical and evolutionary timescales using geometric singular perturbation methods. We show that the selection gradient is constant in the relevant timescale and that it depends only on the resident phenotype, individual growth-rates, equilibrium population densities and reproductive values, all of which are calculated from the resident dynamics. Furthermore, we relate our results to previous work and discuss the theoretical tools required to address such problems. Our work contributes to the theoretical foundations of evolutionary ecology.
Deep learning performance for digital terrain model generation

Traditional methods of photogrammetric image processing allow reconstructing a digital terrain model with high accuracy needed for producing different geographic information system (GIS) products such as maps, orthophoto etc. The accuracy of correspondence problem solution for good imaging conditions can reach the level of hundredth of a pixel. Recently deep learning techniques have been applied for dense stereo matching of images. They allow receiving depth information directly from stereo images and show impressive results for such tasks as scene segmentation, object detection and classification. The aim of the study was to evaluate the performance of deep learning techniques for accurate digital terrain models generation. Some of the state-of-the-art deep learning stereo matching models were evaluated along with original convolutional network. To get reliable accuracy estimation of the considered techniques the results of 3D reconstruction were compared with the reference surface obtained by 3D scanning. Also the imagery acquired from unmanned aerial vehicle during the mission on digitizing an archaeological site was used for performance evaluation by comparing with digital terrain model generated by photogrammetric technique.
A survey on online kernel selection for online kernel learning

Online kernel selection is fundamental to online kernel learning. In contrast to offline kernel selection, online kernel selection intermixes kernel selection and training at each round of online kernel learning, and requires a sublinear regret bound and low computational complexity. In this paper, we first compare the difference between offline kernel selection and online kernel selection, then survey existing online kernel selection approaches from the perspectives of formulation, algorithm, candidate kernels, computational complexities and regret guarantees, and finally point out some future research directions in online kernel selection.
Genomic diversity of the brazilian strains of Streptococcus agalactiae isolated From outbreaks on fish farms

A tilapia do Nilo e o peixe mais produzido no Brasil e a expansao de seu cultivo e afetada pelo patogeno Streptococcus agalactiae. Os objetivos dessa dissertacao foram realizar uma revisao de literatura sobre estreptococose por S. agalactiae e sua epidemiologia, e analisar a populacao brasileira desse micro-organismo, estabelecer uma ferramenta para rastrear surtos de estreptococose e distinguir amostras geneticamente proximas. Um total de 39 amostras foram obtidas de surtos e seus genomas foram sequenciados e anotados para analises comparativas de tipagem multilocus (MLST), similaridade genomica, MLST de genoma inteiro (wgMLST) e uma analise evolutiva com inferencia Bayesiana da especie. Os isolados brasileiros de S. agalactiae apresentaram dois STs, dentre os quais um novo descrito pela primeira vez nesse trabalho, e tambem uma linhagem nao tipavel. O wgMLST diferenciou cada isolado como um clone unico e estabeleceu correlacoes temporais e geograficas entre as amostras, sendo que os STs 260 e 927 prevaleceram no Nordeste e as amostras nao tipaveis, na regiao Centro-Sul. A analise evolutiva Bayesiana mostrou que a populacao brasileira de S. agalactiae tem uma emergencia muito recente, de cerca de 585 anos. A populacao brasileira de S. agalactiae se mostrou genomicamente heterogenea e distribuida em diferentes regioes do pais conforme seu genotipo, e o wgMLST pode rastrear cada evento de surto individualmente.