Miracle-dz/UniFAR-FTUs huggingface dataset:
Single-cell RNA-sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis

Pulmonary fibrosis is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix. In order to comprehensively define the cell types, mechanisms and mediators driving fibrotic remodeling in lungs with pulmonary fibrosis, we performed single-cell RNA-sequencing of single-cell suspensions from 10 non-fibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell types. We report a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF, and identify several previously unrecognized epithelial cell phenotypes including a KRT5−/KRT17+, pathologic ECM-producing epithelial cell population that was highly enriched in PF lungs. Multiple fibroblast subtypes were observed to contribute to ECM expansion in a spatially-discrete manner. Together these data provide high-resolution insights into the complexity and plasticity of the distal lung epithelium in human disease, and indicate a diversity of epithelial and mesenchymal cells contribute to pathologic lung fibrosis. One Sentence Summary Single-cell RNA-sequencing provides new insights into pathologic epithelial and mesenchymal remodeling in the human lung.
Preparation of Nanocellulose Aerogel from the Poplar (Populus tomentosa) Catkin Fiber

: The effects of chemical pretreatment on the purification of poplar (Populus tomentosa) catkin fiber and the effect of ultrasonic time for the microfibrillarization of poplar catkin fiber (PCF) were studied. The nanocellulose aerogels were prepared by freeze drying the cellulose solutions. The density, porosity, micro morphology, thermal stability and mechanical properties of the aerogels were analyzed. It was found that the dewaxing time of PCF is shorter than that of unsonicated nanocellulose. After the treatment of 0.5 wt% sodium chlorite for 2 h, the lignin of PCF was removed. After the chemical purification, the PCF was treated with 2 and 5 wt% NaOH solution and ultrasonicated for 5 and 10 min, respectively. When the ultrasonic time was 10 min, the diameter of the nanocellulose was 20-25 nm. When the ultrasonic time was 5 min, the aerogels with porous honeycomb structure can be prepared by using the nanocellulose sol of PCF as raw material. The density of the aerogels was only 0.3-0.4 mg/cm3 and the porosities of the aerogels were all larger than 99%. The difference between the pyrolysis temperature of aerogels was small, the elastic modulus of aerogels was 30–52 kPa, and the compressive strength was 22–27 kPa. With the increase of the concentration of NaOH solution (5 wt%) and ultrasonic time (10 min), the elastic modulus of aerogels increased gradually and reached the maximum value of 52 kPa, while the compressive strength reached the maximum value of 27 kPa when the PCF being treated in 5 wt% NaOH solution and was ultrasonicated for 5 min.
Émergence d’une souche de génotype 4d détectée chez des hommes du Québec grâce à la surveillance moléculaire des génotypes du virus de l’hépatite C, de 2001 à 2017

Méthodes : Le LSPQ a procédé de façon prospective à un séquençage de Sanger et à une analyse phylogénétique afin de déterminer les génotypes de VHC dans les échantillons prélevés entre novembre 2001 et décembre 2017. Lorsqu’un agrégat important de G4d fut détecté, des renseignements démographiques, l’état de l’infection au VIH et les résultats d’un test de dépistage de la syphilis ont été analysés.
Nanoapplication of a Resistance Inducer to Reduce Phytophthora Disease in Pineapple (Ananas comosus L.)

Treatment of plants with a variety of abiotic and biotic inducers causes induced resistance to pathogen attack. In this study, the effect of four resistance inducers on plant diseases caused by Phytophthora cinnamomi was screened in vivo initially by using lupin, a susceptible model plant. Lupin pretreated with 0.5 mM salicylic acid (SA) showed effective resistance against P. cinnamomi with restricted lesions. Then, mesoporous silica nanoparticles (MSNs) with particle size around 20 nm and approximate pore size of 3.0 nm were synthesized and functionalized for loading and importing SA to pineapple plantlets. Decanethiol gatekeepers were introduced to the surface of MSNs via glutathione (GSH)–cleavable disulfide linkages to cover the pore entrance, which was confirmed through using Raman spectroscopy. Through free diffusion, the loading efficiency of SA in MSNs gated with gatekeepers was 11.7%, but was lower in MSNs without gatekeepers (8.0%). In addition, in vitro release profile of SA from gatekeeper-capped MSNs indicated that higher concentrations of GSH resulted in more cargo release. Moreover, the experiments in planta showed that the application of MSNs as a resistance inducer delivery system significantly improved pineapple resistance to P. cinnamomi in terms of inhibiting lesion development and improving root growth of infected plants, compared to the use of free SA and MSNs without gatekeepers. The analysis of SA, GSH, and defense-related genes, of PR1 and PR5, further confirmed that the slow and prolonged release of SA from MSNs inside the roots of pineapple plants was achieved through a redox-stimuli release mechanism. Therefore, the application of MSNs with redox-responsive gatekeepers has shown great potential as an efficient tool for delivering chemicals into plants in a controllable way.
The Cannabis Multi-Omics Draft Map Project

Recently we have seen a relaxation of the historic restrictions on the use and subsequent research on the Cannabis plants, generally classified as Cannabis sativa and Cannabis indica. What research has been performed to date has centered on chemical analysis of plant flower products, namely cannabinoids and various terpenes that directly contribute to phenotypic characteristics of the female flowers. In addition, we have seen many groups recently completing genetic profiles of various plants of commercial value. To date, no comprehensive attempt has been made to profile the proteomes of these plants. We report herein our progress on constructing a comprehensive draft map of the Cannabis proteome. To date we have identified over 17,000 potential protein sequences. Unfortunately, no annotated genome of Cannabis plants currently exists. We present a method by which “next generation” DNA sequencing output and shotgun proteomics data can be combined to produce annotated FASTA files, bypassing the need for annotated genetic information altogether in traditional proteomics workflows. The resulting material represents the first comprehensive annotated FASTA for any Cannabis plant. Using this annotated database as reference we can refine our protein identifications, resulting in the confident identification of 13,000 proteins with putative function. Furthermore, we demonstrate that post-translational modifications play an important role in the proteomes of Cannabis flower, particularly lysine acetylation and protein glycosylation. To facilitate the evolution of analytical investigations into these plant materials, we have created a portal to host resources we have developed from proteomic and metabolomic analysis of Cannabis plant material as well as our results integrating these resources. All data for this project is available to view or download at www.CannabisDraftMap. Org
Combined cultivation and single-cell approaches to the phylogenomics of nucleariid amoebae, close relatives of fungi

Nucleariid amoebae (Opisthokonta) have been known since the nineteenth century but their diversity and evolutionary history remain poorly understood. To overcome this limitation, we have obtained genomic and transcriptomic data from three Nuclearia, two Pompholyxophrys and one Lithocolla species using traditional culturing and single-cell genome (SCG) and single-cell transcriptome amplification methods. The phylogeny of the complete 18S rRNA sequences of Pompholyxophrys and Lithocolla confirmed their suggested evolutionary relatedness to nucleariid amoebae, although with moderate support for internal splits. SCG amplification techniques also led to the identification of probable bacterial endosymbionts belonging to Chlamydiales and Rickettsiales in Pompholyxophrys. To improve the phylogenetic framework of nucleariids, we carried out phylogenomic analyses based on two datasets of, respectively, 264 conserved proteins and 74 single-copy protein domains. We obtained full support for the monophyly of the nucleariid amoebae, which comprise two major clades: (i) Parvularia–Fonticula and (ii) Nuclearia with the scaled genera Pompholyxophrys and Lithocolla. Based on these findings, the evolution of some traits of the earliest-diverging lineage of Holomycota can be inferred. Our results suggest that the last common ancestor of nucleariids was a freshwater, bacterivorous, non-flagellated filose and mucilaginous amoeba. From the ancestor, two groups evolved to reach smaller (Parvularia–Fonticula) and larger (Nuclearia and related scaled genera) cell sizes, leading to different ecological specialization. The Lithocolla + Pompholyxophrys clade developed exogenous or endogenous cell coverings from a Nuclearia-like ancestor. This article is part of a discussion meeting issue ‘Single cell ecology’.
Predicting changes in bee assemblages following state transitions in North American drylands

Drylands worldwide are experiencing ecosystem state transitions: the expansion of some ecosystem types at the expense of others. Bees in drylands are particularly abundant and diverse, with potential for large compositional differences and seasonal turnover across ecotones. To better understand how future ecosystem state transitions may influence bees, we compared bee assemblages and their seasonality among three dryland ecosystem types of the southwestern U.S. (Plains grassland, Chihuahuan Desert grassland, and Chihuahuan Desert shrubland). Using passive funnel traps, we caught bees during two-week intervals from March through October during 2002 – 2014. The resulting dataset included 302 bee species and >70,500 individuals. Bee abundance, composition, and diversity differed among ecosystems, indicating the potential for future ecosystem state transitions to alter bee assemblage composition in drylands. We also found strong seasonal turnover in bee species, suggesting that bee phenological shifts may accompany ecosystem state transitions. Common rather than rare species drove the observed trends, and both specialist and generalist bee species were indicators of each ecosystem type or month; these species could be informative sentinels of community-wide responses to future shifts. Our work suggests that predicting the consequences of global change for bee assemblages will require accounting for both within-year and among-ecosystem variation.
Rosenzweig-Macaurther Model with Holling type II Predator Functional Response for Constant Delayed Migration

Predator-prey models describe the interaction between two species, the prey which serves as a food source to the predator. The migration of the prey for safety reasons after a predator attack and the predator in search of food, from a patch to another may not be instantaneous. In this paper, a Rosenzweig-MacAurther model with a Holling-type II predator functional response and time delay in the migration of both species is developed and analysed. Stability analysis of the system shows that depending on the prey growth and prey migration rates either both species go to extinction or co-exist. Numerical simulations show that a longer delay in the migration of the species leads makes the model to stabilize at a slower rate compared to when the delay is shorter. Relevant agencies likethe Kenya Wildlife Service should address factors that slow down migration of species, for example, destruction of natural habitats for human settlement and activities, which may cause delay in migration.
The complete mitochondrial genome of a grasshopper endemic to the Qinghai-Tibet plateau, Uvaroviola multispinosa (Acrididae: Oedipodinae)

Abstract The grasshopper Uvaroviola multispinosa (Acrididae: Oedipodinae), is an agricultural pest to pasture and limitedly distributed in Qinghai-Tibet plateau of China. The complete mitochondrial genome of U. multispinosa is 15,620 bp long, which comprises of 13 protein-coding genes (PCGs), two ribosomal RNA genes, 22 transfer RNA (tRNA) genes and a putative non-coding control region (GenBank accession ID: MK829651). These genes are unequally distributed on different DNA chains, which 23 are located on the majority Chain. The nucleotide composition shows evidently bias (A, C, G, and T was 43.8, 14.8, 10.1, and 31.3%, respectively) with an overall AT content of 75.2%. All PCGs are initiated by ATN codons, among them ATG is the most preferred. Eleven PCGs use a common stop codon of TAA or TAG, whereas the remaining two were terminated with single T as incomplete stop codon. The phylogenetic relationships based on Bayes method showed that U. multispinosa is closely related to Compsorhipis davidiana, which is in accordance with its traditional morphological classification.
Population-specific sequence and expression differentiation in Europeans

Much of the enormous phenotypic variation observed across human populations is thought to have arisen from events experienced as our ancestors peopled different regions of the world. However, little is known about the genes involved in these population-specific adaptations. Here we explore this problem by simultaneously examining population-specific sequence and expression differentiation in four human populations. In particular, we design a branch-based statistic to estimate population-specific differentiation in four populations, and apply this statistic to single nucleotide polymorphism (SNP) and RNA-seq data from Italian, British, Finish, and Yoruban populations. As expected, genome-wide estimates of sequence and expression differentiation each independently recapitulate the known demographic history of these four human populations, highlighting the utility of our statistic for identifying genic targets of population-specific adaptations. Application of our statistic reveals that genes containing large copy number variations (CNVs) have elevated levels of population-specific sequence and expression differentiation, consistent with the hypothesis that gene turnover is a key reservoir of adaptive variation. Further, European genes displaying population-specific sequence and expression differentiation are enriched for functions related to epigenetic regulation, immunity, and reproduction. Together, our findings illustrate that population-specific sequence and expression differentiation in humans may preferentially target genes with CNVs and play important roles in a diversity of adaptive and disease-related phenotypes.
Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion

Expanded CAG/CTG repeats underlie thirteen neurological disorders, including myotonic dystrophy (DM1) and Huntington’s disease (HD). Upon expansion, CAG/CTG repeat loci acquire heterochromatic characteristics. This observation raises the hypothesis that repeat expansion provokes changes to higher order chromatin folding and thereby affects both gene expression in cis and the genetic instability of the repeat tract. Here we tested this hypothesis directly by performing 4C sequencing at the DMPK and HTT loci from DM1 and HD patient-derived cells. Surprisingly, chromatin contacts remain unchanged upon repeat expansion at both loci. This was true for loci with different DNA methylation levels and CTCF binding. Repeat sizes ranging from 15 to 1,700 displayed strikingly similar chromatin interaction profiles. Our findings argue that extensive changes in heterochromatic properties are not enough to alter chromatin folding at expanded CAG/CTG repeat loci. Moreover, the ectopic insertion of an expanded repeat tract did not change three-dimensional chromatin contacts. We conclude that expanded CAG/CTG repeats have little to no effect on chromatin conformation.
HOST RESTRICTION FACTORS IN THE REPLICATION OF TOMBUSVIRUSES: FROM RNA HELICASES TO NUCLEOCYTOPLASMIC SHUTTLING

OF DISSERTATION HOST RESTRICTION FACTORS IN THE REPLICATION OF TOMBUSVIRUSES: FROM RNA HELICASES TO NUCLEOCYTOPLASMIC SHUTTLING Positive-stranded (+)RNA viruses replicate inside cells and depend on many cellular factors to complete their infection cycle. In the meanwhile, (+)RNA viruses face the host innate immunity, such as cell-intrinsic restriction factors that could block virus replication. Firstly, I have established that the plant DDX17-like RH30 DEAD-box helicase conducts strong inhibitory function on tombusvirus replication when expressed in plants and yeast surrogate host. This study demonstrates that RH30 blocks the assembly of viral replicase complex, the activation of RNA-dependent RNA polymerase function of p92pol and viral RNA template recruitment. In addition, the features rendering the abundant plant DEAD-box helicases either antiviral or pro-viral functions in tombusvirus replication are intriguing. I found the reversion of the antiviral function of DDX17-like RH30 DEAD-box helicase and the coopted pro-viral DDX3-like RH20 helicase due to deletion of unique N-terminal domains. The discovery of the sequence plasticity of DEAD-box helicases that can alter recognition of different cis-acting elements in the viral genome illustrates the evolutionary potential of RNA helicases in the arms race between viruses and their hosts. Moreover, I discovered that Xpo1 possesses an anti-viral function and exports previously characterized cell-intrinsic restriction factors (CIRFs) from the nucleus to the replication compartment of tombusviruses. Altogether, in my PhD studies, I found plant RH30 DEAD-box helicase is a potent host restriction factor inhibiting multiple steps of the tombusvirus replication. In addition, I provided the evidence supporting that the Nterminal domain determines the functions of antiviral DDX17-like RH30 DEAD-box helicase and pro-viral DDX3-like RH20 DEAD-box helicase in tombusvirus replication. Moreover, I discovered the emerging significance of the Xpo1-dependent nuclear export pathway in tombusvirus replication.
The role of advanced technology in the assessment of oesophageal function in health and disease

Introduction In the absence of disease on endoscopy and failure to respond to empirical therapy, guidelines recommend manometry and reflux studies; however these investigations often fail to establish the physiological basis of oesophageal symptoms or guide therapy. Advances in technology may help provide insight into oesophageal function in health and disease and in turn direct management. The aim of this thesis was to explore the impact of introducing novel techniques and methodology through High Resolution Manometry (HRM) and prolonged wireless pH monitoring (Bravo). Methods: Bravo Study 1: 110 patients who successfully completed standard catheter-based pH monitoring (C-pH) were compared with 134 patients who failed the study and progressed to 48 hour Bravo. The total reflux time (TR; total % time pH drops below 4) was used as the diagnostic marker of reflux disease. Visceral sensitivity was assessed by Symptom Index (SI) and tolerability was measured with a questionnaire. Study 2: 38 patients who continued to have symptoms of reflux despite negative results with C-pH progressed to prolonged Bravo. ‘Worst day’ and ‘Average cumulative’ 24, 48, 72 and 96 hour Bravo measurements were compared to standard 24 hour C-pH. High Resolution Manometry (HRM) 23 asymptomatic volunteers who underwent HRM were compared to 18 patients presenting with oesophageal symptoms. Measurements of swallow responses were collected by varying workload on the oesophagus (changing bolus volume, consistency and patient position). Normative values from healthy subjects were formulated and were used to investigate patients. A novel dysmotility-symptom association parameter (Dysfunction Symptom Index; D-SI) was formulated. Clinical outcome and final diagnosis were documented at 2 years.
Isolation and characterization of fourteen polymorphic microsatellite markers in the viperine snake Natrix maura

Abstract Nineteen polymorphic microsatellite loci were identified and developed for Natrix maura. Polymorphism was assessed for 120 individuals sampled across four sampling sites from the French Pyrenees Mountains. The number of alleles per locus ranged from 3 to 15, and expected heterozygosity per locus ranged from 0.227 to 0.863. We tested for deviation from Hardy–Weinberg equilibrium and linkage disequilibrium and assessed the presence of null alleles for all loci, resulting in a selection of 14 high‐quality polymorphic markers. These markers will be extremely useful in identifying fine‐scale genetic structures and providing insight into conservation management plans of this species.
Locally acting transcription factors are required for p53-dependent cis-regulatory element activity

The master tumor suppressor p53 controls transcription of a wide-ranging gene network involved in apoptosis, cell cycle arrest, DNA damage repair, and senescence. Recent studies revealed pervasive binding of p53 to cis-regulatory elements (CRE), which are non-coding segments of DNA that spatially and temporally control transcription through the combinatorial binding of local transcription factors (TFs). Although the role of p53 as a strong trans-activator of gene expression is well known, the co-regulatory factors and local sequences acting at p53-bound CREs are comparatively understudied. We designed and executed a massively parallel reporter assay (MPRA) to investigate the effect of transcription factor binding motifs and local sequence context on p53-bound CRE activity. Our data indicate that p53-bound CREs are both positively and negatively affected by alterations in local sequence context and changes to co-regulatory TF motifs. We identified a SP1/KLF family motif located in an intronic p53 CRE that is required for the endogenous expression of the p53-dependent gene CCNG1. We also identified ATF3 as a factor that co-regulates the expression of the p53-dependent gene GDF15 through binding with p53 in an upstream CRE. Loss of either p53 or ATF3 severely reduces CRE activity and alters endogenous GDF15 mRNA levels in the cell. Our data suggests that p53 has the flexibility to cooperate with a variety of transcription factors in order to regulate CRE activity. By utilizing different sets of co-factors across CREs, we hypothesize that p53 activity is guarded against loss of any one regulatory partner allowing for dynamic and redundant control of p53-mediated transcription.