Miracle-dz/UniFAR-FTUs huggingface dataset:
The Mechanistic Role and Therapeutic Potential of microRNA-122 in Alcoholic Liver Disease: A Dissertation

Chronic alcohol use results in accelerated liver injury, leading to alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. However, due to the complex nature of this disease process, a central, druggable mechanism has remained elusive. microRNAs are potent post-transcriptional regulators of gene expression. A single miRNA has the ability to regulate hundreds of pathways simultaneously, defining cellular fate and function. microRNA-122 (miR-122), the most abundant miRNA in hepatocytes, has a demonstrated role as an tumor suppressor, regulator of hepatocyte metabolism, and hepatic differentiation. In this dissertation I demonstrate the role of miR-122 on alcoholic liver disease (ALD) pathogenesis over four parts. In chapter II, I will demonstrate chronic alcoholic patients, free of neoplastic changes, have a reduction of miR-122 and that this miRNA regulates HIF-1α, a determinant of ALD pathogenesis. In chapter III, using hepatocytetropic adeno-associated virus 8 (AAV8) vector, I demonstrate that miR-122 inhibition mimics ALD pathogenesis, and furthermore, using hepatocyte-specific HIF-1α-null (HIF1hepKO) mice that this phenomenon is HIF-1α dependent. Given this finding, in chapter IV, I demonstrate that ectopic expression of miR-122 in vivo can reverse alcoholinduced liver damage, steatosis, and inflammation by directly targeting HIF-1α. Finally, in chapter V, I present evidence that alcohol-induced dysregulation of grainyhead-like proteins 1 and 2 (GRHL2), mediate the inhibition of miR-122 at the transcriptional level. These findings dissect a novel mechanistic regulatory axis of miR-122 and indicate a potential opportunity for restoration of miR-122 as a therapy in early ALD.
Maternal allocation in eggs when counting on helpers in a cooperatively breeding bird

For cooperatively breeding birds, it has been proposed that breeders should reduce their investment in eggs when they count on helpers, because this can be compensated for by helpers provisioning of nestlings. Data from some species have supported this prediction, but this is not the case in others. It has also been proposed that mothers should not reduce but rather increase investment if the presence of helpers enhances the reproductive value of offspring, a pattern that might also influence egg production as long as helpers are predictable for laying females. Here, we studied maternal expenditure in eggs and clutches in the Iberian magpie, to see whether mothers reduce their expenditure at the egg stage in the presence of helpers. Our results show that investment in clutches varied depending on the year, date in the season and age of the mother, but there were no reductions in maternal expenditure per individual egg when they counted on helpers. On the contrary, a pattern emerged in the opposite direction of more investment in eggs associated with the future presence of helpers at the nestling stage. Our data suggest that the predictability of helpers, along with the type of benefits accrued from the contribution of helpers, may be crucial to understanding the reaction of mothers at egg production.
Ecological and taxonomic differences between native and introduced plants of southwestern Ontario

Abstract We compared taxonomic and ecological attributes of native and introduced plants (N = 1330 and 484 species, respectively) of southwestern Ontario, using two regional floras (Essex County and Hamilton-Wentworth Regional Municipality) for distributions, and published sources for ecological attributes. Most exotics (86.4%) originate from Europe and Asia. Exotic species tended to occur in families having just one-to-few species locally. Seven families (Amaranthaceae, Asteraceae, Boraginaceae, Brassicaceae, Caryophyllaceae, Fabaceae, and Malvaceae) were significantly over-represented by exotics compared to the distribution of native species in these families, while exotics were significantly under-represented in six families (Cyperaceae, Fagaceae, Juncaceae, Orchidaceae, Potamogetonaceae, and Ranunculaceae). In habitat comparisons, exotic species were significantly over-represented (compared to native species) in disturbed and degraded habitats and moist substrates, while being under-represented in woodland, thicket, and wetland. Introduced species of southwestern Ontario have life history traits that facilitate success in degraded, disturbed and highly fragmented environments. For example, exotics were significantly over-represented by the following life-history traits: short life span, flowering season of four or more months, hermaphrodite sex habit, and very small fruits (< 5 mm). They were significantly under-represented by the monoecious and dioecious sex habits, a flowering period of two months and less, animal-based seed dispersal, and relatively small fruits (5.1 - 10 mm). A separate analysis of exotic species found only in undisturbed communities, showed these species to be more likely to occur in open and moist habitats, to have a tree habit, and an extended flowering period, and to produce many seeds per fruit (> 7).
Regional and habitat variability in azadirachtin content of Indian neem (Azadirachta indica A. Jusieu)

Azadirachtin content in the seeds of neem (Azadirachta indica A. Jusieu) collected from different regions of India was studied. The concentration of azadirachtin varied from 200 to 16,000 ppm (pg/g of the seed kernel). Azadirachtin content was found to be affected by climate and habitat. Annual variation in azadirachtin content was significant. The highest azadirachtin content was recorded in the neem tree populations growing in the southern part of India.
Chemopreventive potential of minor components of olive oil against cancer

Epidemiological studies have suggested that a diet rich in olive oil is associated with a reduced risk of a number of common cancers. In the last decade significant advances have been made in the understanding of how virgin olive oil may work to prevent cancer. A plethora of olive oil constituents have been identified as effective agents against the initiation, promotion and progression of multistage carcinogenesis. These include minor constituents such as the well-studied tocopherol and carotenoid antioxidants, a number of very efficient antioxidant phenolics (simple phenols-hydroxytyrosol, tyrosol- and linked phenols- secoiridoids, lignans-), the triterpene hydrocarbon squalene and the phytosterol β-sitosterol. Provocative recent studies have revealed that the major antioxidant components of olive oil can also exert important non-antioxidant biological functions. Because the chemopreventive role of olive oil constituents is based on hypotheses and not hard data, it needs to be evaluated and verified in animal models of multistage carcinogenesis and in humans in order to gain a better understanding of the effect of olive oil consumption on human cancer. In this review, the antioxidant activity of a number of minor olive oil components is presented and evidence of their ability to interfere with and modulate cellular pathways important in carcinogenesis is reviewed. The implications of these properties for their cancer chemopreventive potential is discussed.
The California fruits and how to grow them

The Climate of California and its Local Modifications . 9 Why the California Climate Specially Favors the Growth of Fruits 20 The Fruit Soils of California . 29 The Wild Fruits of California . 49 California Mission Fruits . -. 6
Autonomy of Higher Education System: In What Direction We Are Moving?

In the current paper we analyze autonomy of high education. Main question what we ask: exist increase or decrease autonomy of high education in the world. We propose Autonomy Increase Hypothesis (AIH) that was provided with help of evolutionary analysis of phase development autonomy and cluster analysis by autonomy indicator. We analyzed four groups’ indicators by 28 European countries and constructed five clusters with different level of autonomy. Also, we investigated economics sense of each cluster and make conclusion about supporting AIH.
Multiplexed Analysis of Diverse RNA Classes via Hybridization Chain Reaction

Gene circuits are complex biological networks composed of numerous regulatory elements, including transcription factors, mRNAs, and microRNAs. Fluorescent in situ hybridization (FISH) is a powerful method for spatially mapping expression levels of RNA elements within an intact organism, but traditional methods exhibit at least one of the following drawbacks: low signal-to-background, arduous and/or destructive multiplexing, and non-quantitative signal. These issues are all overcome using in situ amplification based on the mechanism of hybridization chain reaction (HCR). With this approach, nucleic acid probes complementary to RNA targets trigger the self-assembly of fluorophore-labeled nucleic acid hairpins into tethered fluorescent amplification polymers. In situ HCR enables straightforward multiplexing, high signal-to-background, and quantitative signal. Here, we address three key scenarios in which HCR enables novel applications for in situ hybridization. First, we address the challenge of sorting cell subpopulations based on mRNA abundance using flow cytometry to enable high-throughput measurement of the signal intensity from individual cells. High signal is required to overcome the background autofluorescence integrated over the volume of each cell. Quantitative HCR signal amplification enables multi-dimensional sorting of mammalian cell lines based on expression levels of multiple target mRNAs. Second, we address the challenge of mapping multiple microRNA and mRNA targets simultaneously. Traditional methods enable mapping of single microRNA targets in isolation and use costly LNA probes with proprietary compositions that differ for each target. Here we develop in situ HCR for multiplexed mapping not only of microRNAs, but of microRNAs and mRNAs together, using non-proprietary 2'OMe-RNA probes for miRNA targets and DNA probes for mRNA targets. Third, to enable studies of gut flora, we address the challenge of mapping spatial relationships between different bacterial species within the intact mouse colon. In situ HCR enables multiplexed discrimination of multiple closely-related Bacteroides species with rRNAs that differ by only a few nucleotides. In summary, this thesis presents in situ HCR as a tool for multiplexed analysis of diverse RNA classes and expands the range of gene circuit regulatory elements that can be spatially and quantitatively mapped.
Limnology and trophic status of glacial lakes in the tropical Andes (Cajas National Park, Ecuador)

The tropical Andes has a high density of glacial lakes that are situated in the high‐altitude paramo (3500–4500 m). Ecological information about such lakes is scant despite the fact that these lakes are an important source of water for drinking, irrigation and electricity generation and feed several major tributaries of the Amazon. In this study, we provide data on a survey of 31 lakes in Cajas National Park (Ecuador). Two of the lakes were monitored monthly during one year. In situ nutrient addition experiments were carried out in three of the lakes. Seasonal monitoring in two lakes revealed a thermal stratification of the water column between October and June, with a small temperature difference between epi‐ and hypolimnion (2–3 °C). Oxygen depletion of the hypolimnion towards the end of the stratification period indicated that no complete mixing of the water column occurred during stratification. There was no evidence of depletion of nutrients in the epilimnion or accumulation in the hypolimnion during stratification. There were also no clear seasonal changes in chlorophyll‐a (Chl‐a) concentration nor in phytoplankton community composition in the two lakes. Inputs of dissolved organic carbon (DOC) from the vegetated catchment resulted in high DOC concentrations (median 2.9 mg L⁻¹) compared to temperate mountain lakes. Water transparency was relatively low, with a median extinction coefficient for photosynthetic active radiation of 0.50 m⁻¹ and for UV‐B radiation of 10.13 m⁻¹. Although the thermocline was deep and water transparency was low, estimates of the critical depth for photosynthesis were deeper than the mean water depth in all lakes, suggesting that phytoplankton was not light limited. The phytoplankton community was dominated by chlorophytes (e.g. Oocystis), diatoms (small Cyclotella spp.) or small colonial cyanobacteria (Aphanocapsa, Merismopedia). The zooplankton community was either dominated by large cladocerans and cyclopoid copepods, or by the calanoid copepod Boeckella occidentalis. Total concentrations of phosphorus (P) and nitrogen (N) were comparable to those in temperate mountain lakes (4–35 μg P L⁻¹ and 162–758 μg N L⁻¹) while Chl‐a concentrations were in the lower range (<1 μg L⁻¹). A large part of the total nutrient pool consists of dissolved organic N and P that appeared to have a low bioavailability to phytoplankton. The median seston N:P ratio of 44, a positive correlation between Chl‐a and total P concentration, as well as nutrient addition assays carried out in three lakes all pointed to P limitation of phytoplankton.
Use of duckweed for waste treatment and animal feed

that aquatic plants demonstrate po tentials for reducing inorganic nutrients in domestic wastewater effluent and animal waste lagoons.1-4 These workers have also suggested that aquatic plants have poten tial for crop development, but the technol ogy required for production, harvesting, and processing has not been developed. Reviews and studies showed that vascu lar aquatic plants have acceptable animal feed qualities, ability to remove nutrients from water, and high production rates.48 One factor in favor of developing aquatic plants as an agricultural crop is the ap parent immunity of some species to pests. For example, Eichhornia crassipis, Spiro dela spp. , Lemna spp. , Wolffia spp. , and Typha latifolia apparently have few serious pests. The costs for pest control would, therefore, be negligible when compared to those for traditional agricultural crops. Rapid human population growth has led to consideration of production of aquatic plants as feed crops and for reducing or ganic and inorganic nutrients in wastewa ter. Biological wastes generated by do mestic stock are estimated to be 2 bil tons/ yr (1.8 bil metric tons/yr) in the U. S.9 Poultry houses may concentrate 250,000 animals, cattle feedlots up to 50,000, and swine parlors, 1,500. Concentrating wastes in small areas creates conditions favorable for economic energy extraction. Growth of aquatic plants may well serve the dual function of extracting nutrients from waste water effluents and producing animal feeds. The economic value of the har
Glucocorticoid Receptor Function and its Role in Tamoxifen Resistance

ii Co-Authorship iii Acknowledgements iv List of Figures vii List of Tables ix List of Abbreviations x Introduction 1 1.1 Breast cancer 1 1.2 Glucocorticoid receptor 1 1.3 GR function and breast development 4 1.4 GR and breast cancer 4 1.5 Unliganded GR 7 1.6 ER and the breast 8 1.7 Tamoxifen in breast cancer treatment 10 1.8 GR and Tamoxifen response 12 1.9 Rationale 13 Experimental Methods 16 2.1 Cell Culture and Treatments 16 2.2 Proliferation Assay 17 2.3 Quantitative Reverse Transcriptase PCR (qRT-PCR) Analysis 18 2.4 WCL Harvest and Western Blot Analysis 19 2.5 Flow Cytometry 20 2.6 ALDEFLUOR Assay 20 2.7 Statistical Analysis 22 Results 23 3.1 Unliganded GR Activity in Normal Human Breast Cells 23 3.1.1 Validation of NR3C1 expression in MCF-10A TRIPZ-shGR cell lines 23 3.1.2 Proliferation is decreased by GR KD but apoptosis is not affected in MCF-10A cells 25 3.1.3 Target selection from EPH4 microarray 26 3.1.4 Expression of additional targets is not responsive to UL GR in MCF-10A cells 28 3.1.5 Expression of BRCA1 and CH25H is not responsive to UL GR in MCF-10A cells 30
Biological effect of a new compound glutaraldehyde disinfectant

Objective:A new compound glutaraldehyde disinfectant consisting of glutaraldehyde,benzyl ammonium bromide surfactant,and anti-corrosive was studied.Its microbiological effect and toxicity were observed in laboratory.Methods:The quantitative and qualitative carrier test and toxic experiment were used in laboratory.Results:The results showed that the compound disinfectant containing glutaraldehyde 750? mg/L with 10 or 7? min contact time could kill more than 99.9% of Staphylococcus aureus,Candida albicans,Escherichia coli and 20? g/L with 120? min contact time could kill 100% of Bacillus subtilis var.niger spore. The compound disinfectant containing glutaraldehyde 20? g/L with 240? min contact time could kill 100% of B.subtilis var.niger spore on medical instruments. Toxic experiment showed that the mouse LD 50 of oral glutaraldehyde was 6? 000? mg/kg body weight.The rate of polychromatic erythrocytes with micronucleus induced by glutaraldehyde showed no difference from the negative control group and no influence on incidence of mouse sperm deformity was observed.Conclusion:The compound glutaraldehyde disinfectant is a substance with no actual toxicity,no mutagenic action.
The anticancer effects of supinoxin (RX-5902) in renal cell cancer.

524 Background: DEAD box RNA helicase DDX5/p68 may play several important roles in cancer. In particular, phosphorylated p68 has been shown to be associated with cell transformation, epithelial mesenchymal transition (EMT), and cell migration, deeming it a promising target for novel anti-cancer therapeutics. We have previously shown that Supinoxin (RX-5902) interacts with phosphorylated p68 on Tyr593, interfering with the phosphorylated p68-β-catenin signaling pathway. Methods: In this study, we first demonstrated anti-proliferative effects in ten renal cancer cell lines with a high level of sensitivity to Supinoxin (IC50 of 39 nM); TK-10 was the only resistant cell line in this study. We also sought to examine the tumor growth inhibition (TGI), tumor growth delay (TGD), and survival benefits of Supinoxin in the human renal cell carcinoma tumor (Caki-1) xenograft mouse model, using two different dosing schemas: weekly dosing at 20-160 mg/kg for 4 weeks, or 50-70 mg/kg daily (5 days on/2 days off) for 3 we.
Leishmania transmission-blocking vaccines: a review.

Objective: To review information on transmission-blocking vaccine against Leishmania infections. Data sources: Peer-reviewed journals and accepted manuscripts in press. Study selection: Laboratory studies based on raising of immune sera against Leishmania-derived antigens using the BALB/c and hamster murine models. Testing of the immune sera for their potential to limit the transmission of cutaneous leishmaniasis in its natural vector Phlebotomus duboscqi. Data synthesis: Leishmania major-derived recombinant 63 kilodalton glycoprotein (rgp63), lipophosphoglycan (LPG), whole parasite, flagella and nuclear fractions; monoclonal antibodies and sandfly gut antigens have all been tested for their candidacy as Leishmania-transmission blocking vaccines. Conclusion: Liposphoglycan proved to be a promising candidate for Leishmania transmission-blocking vaccine studies.
Genetic diversity associated with N-cycle pathways in microbialites from Lake Alchichica, Mexico

Author(s): Alcantara-Hernandez, RJ; Valdespino-Castillo, PM; Centeno, CM; Alcocer, J; Merino-Ibarra, M; Falcon, LI | Abstract: © Inter-Research 2017. Microbialites are an example of complex and diverse microbial assemblages where several metabolic pathways are interconnected for biomass formation coupled to mineral precipitation. Lake Alchichica (Mexico) is an oligotrophic environment where nitrogen (N) and phosphorus alternately limit productivity, and massive microbialite growths are found along the lake's perimeter. Previous studies have described the importance of N2 fixation in these microbialites, although other pathways associated with the N cycle, including denitrification, nitrification and anaerobic ammonium oxidation (anammox), had not been evaluated. This study identified the genetic diversity associated with N cycling in both metagenomic DNA and RNA expression by targeting key genes for nitrogenase (nifH), ammonia monooxygenase (amoA), nitrite oxidoreductase (nxrA, nxrB), hydrazine oxidoreductase (hzo) and nitrite (nirS and nirK) and nitrous oxide (nosZ) reductases. While the genetic potential for N2 fixation, ammonia oxidation, anammox and denitrification was present in the microbialites of Lake Alchichica, the most transcribed pathway was N2 fixation.
Rôle du métabolisme énergétique dans un contexte de vieillissement chez C. elegans

Mutations in the DNA/RNA binding proteins TDP-43 and FUS are associated with Amyotrophic Lateral Sclerosis and Frontotemporal Lobar Degeneration. Intracellular accumulations of wild type TDP-43 and FUS are observed in a growing number of late-onset diseases suggesting that TDP-43 and FUS proteinopathies may contribute to multiple neurodegenerative diseases. To better understand the mechanisms of TDP-43 and FUS toxicity we have created transgenic Caenorhabditis elegans strains that express full-length, untagged human TDP-43 and FUS in the worm’s GABAergic motor neurons. Transgenic worms expressing mutant TDP-43 and FUS display adult-onset, age-dependent loss of motility, progressive paralysis and neuronal degeneration that is distinct from wild type alleles. Additionally, mutant TDP-43 and FUS proteins are highly insoluble while wild type proteins remain soluble suggesting that protein misfolding may contribute to toxicity. Populations of mutant TDP-43 and FUS transgenics grown on solid media become paralyzed over 7 to 12 days. We have developed a liquid culture assay where the paralysis phenotype evolves over several hours. We introduce C. elegans transgenics for mutant TDP-43 and FUS motor neuron toxicity that may be used for rapid genetic and pharmacological suppressor screening. Citation: Vaccaro A, Tauffenberger A, Aggad D, Rouleau G, Drapeau P, et al. (2012) Mutant TDP-43 and FUS Cause Age-Dependent Paralysis and Neurodegeneration in C. elegans. PLoS ONE 7(2): e31321. doi:10.1371/journal.pone. 0031321 Editor: Leonard Petrucelli, Mayo Clinic, United States of America Received October 11, 2011; Accepted January 5, 2012; Published February 21, 2012 Copyright: ! 2012 Vaccaro et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This research was supported by: Montreal University Hospital Foundation (http://fondationduchum.com/fr) to JAP, Natural Sciences and Engineering Research Council Discovery Grant (http://www.nserc-crsng.gc.ca) to JAP, Canadian Institutes of Health Research New Investigator (http://www.cihr-irsc.gc.ca) to JAP, Frick Foundation for ALS Research (http://frick-fondation.ch) to PD and JAP and a Bernice Ramsay Discovery Grant from the ALS Society of Canada (http:// www.als.ca/) to JAP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. *
Effects of Antioxidants on the Oxidative Stability of Vegetable Oil at Elevated Temperature

Unstable nature of vegetable oil posed serious health risk to humans. The oxidative stability of vegetable oils (Palm Olein, Soyabean Oil and Linseed Oil) with direct incorporation of antioxidants (tertiary butyl hydroxoquinone (TBHQ), butylated hydroxyl toluene (BHT) and mixed (TBHQ and BHT) at room temperature and 70 0 C for 168 hours was aimed to be investigated. Peroxide value was determined and the oxidative stability was evaluated. TBHQ had significant effect on the oxidative stability of palm olein at 70 0 C while (TBHQ and BHT) had synergetic effect on stability of Soya bean oil at room temperature and Linseed oil at 70 0 C.