Miracle-dz/UniFAR-FTUs huggingface dataset:
Utility of cell-free DNA concentrations and illness severity scores to predict survival in critically ill neonatal foals

Plasma cell-free DNA (cfDNA) levels have been associated with disease and survival status in septic humans and dogs. To date, studies investigating cfDNA levels in association with critical illness in foals are lacking. We hypothesized that cfDNA would be detectable in the plasma of foals, that septic and sick-nonseptic foals would have significantly higher cfDNA levels compared to healthy foals, and that increased cfDNA levels would be associated with non-survival. Animals used include 80 foals of 10 days of age or less admitted to a tertiary referral center between January and July, 2020 were stratified into three categories: healthy (n=34), sick non-septic (n=11) and septic (n=35) based on specific criteria. This was a prospective clinical study. Blood was collected from critically ill foals at admission or born in hospital for cfDNA quantification and blood culture. Previously published sepsis score (SS) and neonatal SIRS score (NSIRS) were also calculated. SS, NSIRS, blood culture status and cfDNA concentrations were evaluated to predict survival. Continuous variables between groups were compared using Kruskal-Wallis ANOVA with Dunn’s post hoc test. Comparisons between two groups were assessed using the Mann-Whitney U-test or Spearman rank for correlations. The performance of cfDNA, sepsis score and NSIRS score to predict survival was assessed by receiver operator characteristic (ROC) curve analysis including area under the curve, sensitivity and specificity using cutoffs. Plasma cfDNA was detectable in all foals. No significant differences in cfDNA concentration were detected between healthy foals and septic foals (P=0.65) or healthy foals and sick non-septic foals (P=0.88). There was no significant association between cfDNA and culture status, SS, NSIRS or foal survival. SS (AUC 0.85) and NSIRS (AUC 0.83) were superior to cfDNA (AUC 0.64) in predicting survival. cfDNA was detectable in foal plasma however offers negligible utility to diagnose sepsis or predict survival in critical illness in neonates.
Verification of Dispersion Model on Anaerobic Reaction Simulation

A dispersion model was established on the combination of biological reaction and related physical-operational characteristics, such as dispersion, diffusion, cell accumulation and transportation. Also, the feasibility of the dispersion model in anaerobic filter digester simulation was identified. Under low loading rate and without recirculation, the digester behaves like a plug flow reactor. Therefore, the simulated results of dispersion model and plug flow model are similiar. However, at higher loading rate, the dispersion of digester increases, and the simulated results of the dispersion model are closer to experimental data than the plug model. That proved the applicability of dispersion model in anaerobic reaction simulation.
The Discomfort of Riding Shotgun – Why Many People Don’t Like to Be Co-driver

This work investigates which conditions lead to co-driver discomfort aside from classical motion sickness, what characterizes uncomfortable situations, and why these conditions have a negative effect. The automobile is called a “passenger vehicle” as its main purpose is the transportation of people. However, passengers in the car are rarely considered in research concerning driving discomfort. The few studies in this area focus on driver discomfort, automated vehicles, or driver assistant systems. An earlier public survey indicated that discomfort is also a relevant problem for co-drivers. In this paper, these results are confirmed and extended through an online questionnaire with N = 119 participants and a detailed follow-up interview study with N = 24 participants was conducted. The results of the online questionnaire show that co-driver discomfort is a widespread problem (88%). The interviews indicate that the driving style is one factor contributing to co-driver discomfort, in particular close following or fast driving. In those situations, participants experienced a feeling of being exposed, which additionally contributed to their discomfort. Uncomfortable situations were also perceived as safety critical. A model for possible cognitive origins of discomfort in co-drivers, extending theories from the areas of stress and self-regulation, is developed based on the results. Co-driver discomfort is a common problem, highlighting the relevance of further research on supporting co-drivers. The reported correlations and the proposed model can help to explain the origin of this discomfort. The results provide a foundation for the future design of interventions like human machine interfaces aiming at reducing co-driver discomfort.
The Attentive Cursor Dataset

Powered by TCPDF (www.tcpdf.org) This material is protected by copyright and other intellectual property rights, and duplication or sale of all or part of any of the repository collections is not permitted, except that material may be duplicated by you for your research use or educational purposes in electronic or print form. You must obtain permission for any other use. Electronic or print copies may not be offered, whether for sale or otherwise to anyone who is not an authorised user. Leiva, Luis; Arapakis, Ioannis
Dynamics, cariogenicity, and geographic distribution of Streptococcus mutans adhesin types suggest adaptation to individual hosts

Dental caries, the most common chronic infectious disease, involve Streptococcus mutans SpaP A/B/C and Cnm/Cbm adhesin types of different virulence. We have explored their stability and dynamics over 5 years, their geographic distribution, as well as the potentially increased cariogenicity of specific SpaP B subtypes. We performed qPCR and TaqMan typing using whole saliva and isolates from 452 Swedish adolescents followed from 12 to 17 years of age. Approximately 50% of the children were infected at baseline with a single dominant (44%) or mixed (6%) SpaP A, B, or C type, some of which were also Cnm (6%) or Cbm (1%) positive. Stability (+, +) was high for S. mutans infection (85%) and dominant SpaP A or C (80% and 67%) and Cnm or Cbm (85% and 100%) types, but low for SpaP B (51%) and mixed SpaP A/B/C types (26%). Only five children switched from one SpaP type to another, and none between Cnm and Cbm types. Mixed SpaP A/B/C types were typically lost or changed into dominant types. Moreover, children infected with Cnm (n=26) types were more frequent in the northern (Skellefteå) region (p = 0.0041), and those with Cbm types (n=7) in the southern (Umeå) region. Children infected with SpaP B-2 subtypes had a doubled caries experience (p = 0.009) and 5-year caries increment (p = 0.02) compared to those infected with SpaP A. In conclusion, the stable dominant but instable mixed adhesin types and geographic differentiation of Cnm and Cbm types suggest adaptation of low and high cariogenicity types to specific individuals.
Short-range template switching in great ape genomes explored using pair hidden Markov models

Many complex genomic rearrangements arise through template switch errors, which occur in DNA replication when there is a transient polymerase switch to an alternate template nearby in three-dimensional space. While typically investigated at kilobase-to-megabase scales, the genomic and evolutionary consequences of this mutational process are not well characterised at smaller scales, where they are often interpreted as clusters of independent substitutions, insertions and deletions. Here we present an improved statistical approach using pair hidden Markov models, and use it to detect and describe short-range template switches underlying clusters of mutations in the multi-way alignment of hominid genomes. Using robust statistics derived from evolutionary genomic simulations, we show that template switch events have been widespread in the evolution of the great apes’ genomes and provide a parsimonious explanation for the presence of many complex mutation clusters in their phylogenetic context. Larger-scale mechanisms of genome rearrangement are typically associated with structural features around breakpoints, and accordingly we show that atypical patterns of secondary structure formation and DNA bending are present at the initial template switch loci. Our methods improve on previous non-probabilistic approaches for computational detection of template switch mutations, allowing the statistical significance of events to be assessed. By specifying realistic evolutionary parameters based on the genomes and taxa involved, our methods can be readily adapted to other intra- or inter-species comparisons.
iSMNN: Batch Effect Correction for Single-cell RNA-seq data via Iterative Supervised Mutual Nearest Neighbor Refinement

Batch effect correction is an essential step in the integrative analysis of multiple single cell RNA-seq (scRNA-seq) data. One state-of-the-art strategy for batch effect correction is via unsupervised or supervised detection of mutual nearest neighbors (MNNs). However, both two kinds of methods only detect MNNs across batches on the top of uncorrected data, where the large batch effect may affect the MNN search. To address this issue, we presented iSMNN, a batch effect correction approach via iterative supervised MNN refinement across data after correction. Our benchmarking on both simulation and real datasets showed the advantages of the iterative refinement of MNNs on the performance of correction. Compared to the popular methods MNNcorrect and Seurat v3, our iSMNN is able to better mix the cells of the same cell type across batches. In addition, iSMNN can also facilitate the identification of DEGs relevant to the biological function of certain cell types. These results indicated that iSMNN will be a valuable method for integrating multiple scRNA-seq datasets that can facilitate biological and medical studies at single-cell level.
Polymer-clay nanocomposites: current status and challenges

The key to the performance of polymer nanocomposites is the quality of dispersion of the nano-reinforcement particles and the interfacial interaction between the matrix and the reinforcement phase. Optimisation of these properties requires various special and complicated treatments, which are not always easy to determine. Often property enhancement is not as significant as expected by the industry for the use of these nanocomposites. The present paper aims to provide an overview of the current status of these materials in terms of their development and production. Examples have been provided for the production of thermoplastic, thermoset and biodegradable polymer nanocomposites by different means, such as melt blending and in-situ polymerisation. It also focusses on properties enhancement reported by different researchers and future challenges for these emerging materials in engineering applications.
Badger territoriality maintained despite disturbance of major road construction

Road ecology has traditionally focused on the impact of in-situ and functional roads on wildlife. However, road construction also poses a major, yet understudied, threat and any implications for key aspects of animal behaviour are unknown. There are also concerns that environmental disturbances, including major roadworks, can disrupt badger territoriality, promoting the spread of tuberculosis to cattle. To address these knowledge gaps, the ranging behaviour of a medium-density Irish badger population was monitored, using GPS-tracking collars, before, during and after a major road realignment project that bisected the study area. We estimated badgers’ home range sizes, nightly distances travelled and the distance and frequency of extra-territorial excursions during each phase of the study and quantified any changes to these parameters. We show that roadworks had a very limited effect on ranging behaviour. A small increase in nightly distance during the roadworks did not translate into an increase in home range size, nor an increase in the distance or frequency of extra-territorial excursions during the roadworks. In addition, suitable mitigation measures to prevent badger deaths appeared to ensure that normal patterns of ranging behaviour continued once the new road was in place. Our analysis supports the view that road construction did not cause badgers to change their ranging behaviour in ways likely to increase the spread of tuberculosis.
Sphingolipid changes in Parkinson L444P GBA mutation fibroblasts promote α-synuclein aggregation

Intraneuronal accumulation of aggregated α-synuclein is a pathological hallmark of Parkinson’s disease. Therefore, mechanisms capable of promoting α-synuclein deposition bear important pathogenetic implications. Mutations of the glucocerebrosidase 1 (GBA) gene represent a prevalent Parkinson’s disease risk factor. They are associated with loss of activity of a key enzyme involved in lipid metabolism, glucocerebrosidase, supporting a mechanistic relationship between abnormal α-synuclein-lipid interactions and the development of Parkinson pathology. In this study, the lipid membrane composition of fibroblasts isolated from control subjects, patients with idiopathic Parkinson’s disease (iPD) and Parkinson patients carrying the L444P GBA mutation (PD-GBA) was assayed using shotgun lipidomics. The lipid profile of PD-GBA fibroblasts differed significantly from that of control and iPD cells. It was characterized by an overall increase in sphingolipid levels. It also featured a significant change in the proportion of ceramide, sphingomyelin and hexosylceramide molecules with shorter and longer hydrocarbon chain length; levels of shorter-chain molecules were increased while the percent of longer-chain sphingolipids was decreased in PD-GBA lipid extracts. The extent of this shift was correlated to the degree of reduction of fibroblast glucocerebrosidase activity. In a second set of experiments, lipid extracts from control and PD-GBA fibroblasts were added to incubations of recombinant α-synuclein. The kinetics of α-synuclein aggregation, as assessed by the binding of thioflavin T to amyloid structures, was significantly accelerated after addition of PD-GBA extracts as compared to control samples. Amyloid fibrils collected at the end of these incubations contained lipids, indicating α-synuclein-lipid co-assembly. Lipids extracted from α-synuclein fibrils were also analysed by shotgun lipidomics. Data revealed that the lipid content of these fibrils was significantly enriched of shorter-chain sphingolipids. Taken together, findings of this study indicate that the L444P GBA mutation and consequent enzymatic loss are associated with a distinctly altered membrane lipid profile that provides a biological fingerprint of this mutation in Parkinson fibroblasts. This altered lipid profile, which includes an increased content of shorter-chain sphingolipids, could also be an indicator of increased risk for α-synuclein aggregate pathology. Shorter-chain molecules may act as preferred reactants during lipid-induced α-synuclein fibrillation.
Molecular phylogenetics and character evolution in Haplanthodes (Acanthaceae), an endemic genus from peninsular India

Haplanthodes (Acanthaceae) is an Indian endemic genus with four species. It is closely related to Andrographis which is also mainly distributed in India. Haplanthodes differs from Andrographis by the presence of cladodes in the inflorescences, sub actinomorphic flowers, stamens included within the corolla tube, pouched stamens and oblate pollen grains. To understand the phylogenetic relationship of Haplanthodes with Andrographis and Haplanthus, another related genus, we used four plastid markers, matK, rbcL, psbA-trnH and trnGR to construct a molecular phylogeny. Our results established the monophyly of this genus and revealed a sister relationship to Andrographis and Haplanthus. Further, to understand the historical biogeography of the genus, we inferred the divergence time and performed ancestral area reconstruction. Our analyses suggest that Haplanthodes has evolved during Late Miocene 5.85 Ma [95%HPD: 2.18-10.34 Ma] in peninsular India where it might have shared a common ancestor with Andrographis. To understand character evolution, the ancestral states of important morphological characters were inferred based on the equal rate model and discussed. The generic status of Haplanthus is not resolved due to incomplete sampling.
Identification of cell-type-specific marker genes from co-expression patterns in tissue samples

Motivation Marker genes, defined as genes that are expressed primarily in a single cell type, can be identified from the single cell transcriptome; however, such data are not always available for the many uses of marker genes, such as deconvolution of bulk tissue. Marker genes for a cell type, however, are highly correlated in bulk data, because their expression levels depend primarily on the proportion of that cell type in the samples. Therefore, when many tissue samples are analyzed, it is possible to identify these marker genes from the correlation pattern. Results To capitalize on this pattern, we develop a new algorithm to detect marker genes by combining published information about likely marker genes with bulk transcriptome data in the form of a semi-supervised algorithm. The algorithm then exploits the correlation structure of the bulk data to refine the published marker genes by adding or removing genes from the list. Availability and implementation We implement this method as an R package markerpen, hosted on https://github.com/yixuan/markerpen. Contact roeder@andrew.cmu. edu
Highly conserved and cis-acting lncRNAs produced from paralogous regions in the center of HOXA and HOXB clusters in the endoderm lineage

Long noncoding RNAs (lncRNAs) have been shown to play important roles in gene regulatory networks acting in early development. There has been rapid turnover of lncRNA loci during vertebrate evolution, with few human lncRNAs conserved beyond mammals. The sequences of these rare deeply conserved lncRNAs are typically not similar to each other. Here, we characterize HOXA-AS3 and HOXB-AS3, lncRNAs produced from the central regions of the HOXA and HOXB clusters. Sequence-similar homologs of both lncRNAs are found in multiple vertebrate species and there is evident sequence similarity between their promoters, suggesting that the production of these lncRNAs predates the duplication of the HOX clusters at the root of the vertebrate lineage. This conservation extends to similar expression patterns of the two lncRNAs, in particular in cells transiently arising during early development or in the adult colon, and their co-regulation by the CDX1/2 transcription factors. Functionally, the RNA products of HOXA-AS3 and HOXB-AS3 regulate the expression of their overlapping HOX5–7 genes both in HT-29 cells and during differentiation of human embryonic stem cells. Beyond production of paralogous protein-coding and microRNA genes, the regulatory program in the HOX clusters therefore also relies on paralogous lncRNAs acting in restricted spatial and temporal windows of embryonic development and cell differentiation.
Multi-resolution characterization of molecular taxonomies in bulk and single-cell transcriptomics data

As high-throughput genomics assays become more efficient and cost effective, their utilization has become standard in large-scale biomedical projects. These studies are often explorative, in that relationships between samples are not explicitly defined a priori, but rather emerge from data-driven discovery and annotation of molecular subtypes, thereby informing hypotheses and independent evaluation. Here, we present K2Taxonomer, a novel unsupervised recursive partitioning algorithm and associated R package that utilize ensemble learning to identify robust subgroups in a “taxonomy-like” structure (https://github.com/montilab/K2Taxonomer). K2Taxonomer was devised to accommodate different data paradigms, and is suitable for the analysis of both bulk and single-cell transcriptomics data. For each of these data types, we demonstrate the power of K2Taxonomer to discover known relationships in both simulated and human tissue data. We conclude with a practical application on breast cancer tumor infiltrating lymphocyte (TIL) single-cell profiles, in which we identified co-expression of translational machinery genes as a dominant transcriptional program shared by T cells subtypes, associated with better prognosis in breast cancer tissue bulk expression data.
SlSWEET15 exports sucrose from phloem and seed coat in tomato to supply carbon for fruit and seed development

Tomato, an important fruit crop worldwide, requires efficient sugar allocation for fruit development. However, molecular mechanisms for sugar import to fruits remain poorly understood. Expression of SWEET (Sugars Will Eventually be Exported Transporters) proteins is closely linked with hexose ratio in tomato fruits and may be involved in sugar allocation. Here, using quantitative PCR, we discovered that SlSWEET15 was highly expressed in developing fruits compared to vegetative organs. Based on in situ hybridization and GUS fusion analyses, SlSWEET15 proteins accumulated in vascular tissues and seed coats, major sites of sucrose unloading in fruits. Localizing SlSWEET15-GFP to the plasma membrane supported its putative role in apoplasmic sucrose unloading. The sucrose transport activity of SlSWEET15 was confirmed by complementary growth assays in a yeast mutant. Elimination of the SlSWEET15 function by CRISPR/cas9 gene editing significantly decreased average sizes and weights of fruits, with severe defects in seed filling and embryo development. Together, we confirmed the role of SlSWEET15 in mediating sucrose efflux from the releasing phloem to the fruit apoplasm and subsequent import into parenchyma cells during fruit development. Furthermore, SlSWEET15-mediated sucrose efflux was also required for sucrose unloading from the seed coat to the developing embryo. One-sentence Summary SlSWEET15, a specific sucrose uniporter in tomato, mediates apoplasmic sucrose unloading from releasing phloem cells and seed coat for carbon supply during fruit expansion and seed filling.
Single-molecule analysis reveals cooperative stimulation of Rad51 filament nucleation and growth by mediator proteins

Homologous recombination (HR) is an essential DNA double-strand break (DSBs) repair mechanism frequently inactivated in cancer. During HR, RAD51 forms nucleoprotein filaments on RPA-coated resected DNA and catalyses strand invasion into homologous duplex DNA. How RAD51 displaces RPA and assembles into long HR-proficient filaments remains uncertain. Here, we employ single-molecule imaging to investigate the mechanism of nematode RAD-51 filament growth in the presence of BRC-2 (BRCA2) and RAD-51 paralogs, RFS-1/RIP-1. BRC-2 nucleates RAD-51 on RPA-coated DNA, while RFS-1/RIP-1 acts as a ‘chaperone’ to promote 3’ to 5’ filament growth via highly dynamic engagement with 5’ filament ends. Inhibiting ATPase or mutation in RFS-1 Walker box leads to RFS-1/RIP-1 retention on RAD-51 filaments and hinders growth. rfs-1 Walker box mutants display sensitivity to DNA damage and accumulate RAD-51 complexes non-functional for HR in vivo. Our work reveals the mechanism of RAD-51 nucleation and filament growth in the presence of recombination mediators.