Miracle-dz/UniFAR-FTUs huggingface dataset:
Miconazole resistance in fungal biofilms : a molecular point of view

The interest in fungal biofilm formation and in the resistance of fungal biofilms against antimicrobial agents has increased due to the expanding problem of biofilm-related infections. In this doctoral research the activity of miconazole against biofilms of Candida species has been investigated. Furthermore, we have focused on the molecular mechanisms involved in fungal biofilm formation and in resistance to miconazole. The data showed that miconazole has a fungicidal activity against Candida spp. biofilms. The exact mechanism leading to cell death could not be elucidated, and possibly includes other mechanisms than increased ROS levels. Notwithstanding the fungicidal activity of miconazole against Candida spp. biofilms, we noticed a resistant fraction (1% - 10%) of sessile cells that was able to survive a high dose of miconazole. The molecular mechanisms of biofilm formation and the resistance to miconazole were unraveled by screening a S. cerevisiae deletion mutant bank. The results of the screening highlighted the multi-factorial complexity of biofilm formation and resistance. An in depth analysis of the results revealed that two major biological processes play an important role in S. cerevisiae biofilm formation and the susceptibility to miconazole, i.e. the organization of two types of organelles, the mitochondria and the peroxisomes. Furthermore, we demonstrated that phytosphingosine-1-phosphate has a protective effect against miconazole treatment. Experiments in C. albicans indicated that this intermediate of the sphingolipid biosynthesis acts as a signaling molecule enhancing the export of miconazole. This doctoral research showed that miconazole has a fungicidal activity against Candida spp. biofilms and unraveled the mechanisms involved in fungal biofilm formation and resistance to miconazole.
Peptide Folding and Binding Probed by Systematic Non-canonical Mutagenesis

Many proteins and peptides fold upon binding another protein. Mutagenesis has proved an essential tool in the study of these multi-step molecular recognition processes. By comparing the biophysical behavior of carefully selected mutants, the concert of interactions and conformational changes that occur during folding and binding can be separated and assessed. Recently, this mutagenesis approach has been radically expanded by deep mutational scanning methods, which allow for many thousands of mutations to be examined in parallel. Furthermore, these high-throughput mutagenesis methods have been expanded to include mutations to non-canonical amino acids, returning peptide structure-activity relationships with unprecedented depth and detail. These developments are timely, as the insights they provide can guide the optimization of de novo cyclic peptides, a promising new modality for chemical probes and therapeutic agents.
Pretest studies for a microbially enhanced oil recovery field pilot in a hypersaline oil reservoir

Abstract The ecological and physiological factors governing microbial activity in the Southeast Vassar Vertz Sand Unit (SEWSU), Payne County, OK, an oil reservoir selected for a microbially enhanced oil recovery field pilot, were studied. Analysis of the brines from the reservoir showed that the SEWSU reservoir is a hypersaline environment rich in calcium and magnesium cations, and contains most of the inorganic nutrients required for microbial growth. Substantial amounts of sulfate and sulfide were detected in the brines, indicating a potential for sulfate reduction activity. Of the various carbohydrate‐based nutrients tested, a molasses‐ammonium nitrate nutrient mixture best stimulated the metabolism and growth of the microbial communities in the brines. Sulfide was not detected in any brine samples that received high levels of nitrate, even when additional carbon sources such as molasses were added. The addition of nitrate also resulted in shorter lag times, higher maximum turbidities, and larger press.
Role of Sole Similarity of Top Management Team on International Shipping Transporting Network

ABSTRACT Pi, S. ; Hu, Z. ; Peng, L. , and Liang, J., 2020. Role of sole similarity of top management team on international shipping transporting network. In: Yang, Y. ; Mi, C. ; Zhao, L. , and Lam, S. (eds.), Global Topics and New Trends in Coastal Research: Port, Coastal and Ocean Engineering. Journal of Coastal Research, Special Issue No. 103, pp. 624–628. Coconut Creek (Florida), ISSN 0749-0208. By proposing a new construct of sole similarity in top management team personal network, this paper attempt to reveal the scientific law that how the relationship between the interpersonal network of TMT and the external network of international shipping firms affects the growth of performance. We calculated 17-year data from Chinese listed companies, constructing the sole similarity of TMT network by 2-mode network method. The results indicate that the diversity of the external network of firms has an overshadowing effect on the sole similarity TMT and the performance of the enterprise. This study integrates the two theoretical perspectives of the heterogeneity and interaction of the TMT, reveals that the sole similarity of the TMT has a “double-edged sword” effect on the enterprise, improves the relevant theories of the TMT.
Knockdown of DDX46 inhibits trophoblast cell proliferation and migration through the PI3K/Akt/mTOR signaling pathway in preeclampsia

Abstract Preeclampsia (PE) is a serious disease during pregnancy associated with the dysfunction of trophoblast cell invasion. DDX46 is a kind of RNA helicase that has been found to regulate cancer cell metastasis. However, the role of DDX46 in PE remains unclear. Our results showed that the mRNA levels of DDX46 in placental tissues of pregnant women with PE were markedly lower than those in normal pregnancies. Loss-of-function assays showed that knockdown of DDX46 significantly suppressed cell proliferation of trophoblast cells. Besides, DDX46 knockdown decreased trophoblast cell migration and invasion capacity. In contrast, the overexpression of DDX46 promoted the migration and invasion of trophoblast cells. Furthermore, knockdown of DDX46 caused significant decrease in the levels of p-PI3K, p-Akt, and p-mTOR in HTR-8/SVneo cells. In addition, treatment with IGF-1 reversed the inhibitory effects of DDX46 knockdown on proliferation, migration, and invasion of HTR-8/SVneo cells. In conclusion, these data suggest that DDX46 might be involved in the progression of PE, which might be attributed to the regulation of PI3K/Akt/mTOR signaling pathway. Thus, DDX46 might serve as a therapeutic target for the treatment of PE.
Distribution and community structure of microphytoplankton in relation to increasing anthropogenic impact along coastal waters of Jeddah, the central Red Sea

Abstract Seasonal distribution and diversity of surface phytoplankton have been studied in relation to anthropogenic activities at seven locations along the coastal waters of Jeddah, Saudi Arabia in 2017. The concentration of nitrite, nitrate, ammonia, phosphate and silicate varied over wide ranges: 0.04–20.27, 0.05–29.3, 0.22–78.16, 0.02–25.90 and 43–24.50 μmol l−1, respectively. Inorganic nutrients, phytoplankton biomass and density were at eutrophic levels at two lagoon locations (4 and 5), while other coastal locations showed oligotrophic characteristics of the Red Sea. Phytoplankton biomass was positively correlated with all measured inorganic nutrients. The total phytoplankton density varied between 52.4 × 103 and 40800 × 103 cells m−3 (average 6249.9×103 ± 10797×103 cells m−3). A total of 174 species of phytoplankton (95 diatoms, 75 dinoflagellates, 3 cyanophytes and 1 silicoflagellates) were recorded in this study, with the dominance of diatoms (95.1%). Higher densities observed at lagoon locations were mainly due to the proliferation of the diatom species Skeletonema costatum and Chaetoceros decipiens. In terms of diversity, dinoflagellates were more numerous than diatoms in July, otherwise mostly diatoms dominated. On the other hand, cyanophytes were more abundant in November. Based on the present study, anthropogenic activities (especially sewage effluent) in Jeddah coastal waters had a significant impact on the phytoplankton densities and diversity.
The Application of BIM Technology in Budget Control of Port Construction Cost

ABSTRACT Li, Y. and Li, Q. , 2020. The application of BIM technology in budget control of port construction cost. In: Yang, Y. ; Mi, C. ; Zhao, L. , and Lam, S. (eds.), Global Topics and New Trends in Coastal Research: Port, Coastal and Ocean Engineering. Journal of Coastal Research, Special Issue No. 103, pp. 644–648. Coconut Creek (Florida), ISSN 0749-0208. In order to fully alleviate the practical economic pressure of port construction projects and establish a relatively good cost control environment, a budget control method for port construction projects based on BIM technology is proposed. Taking the selected area as the target research scope, through the definition of representative cost engineering, the standardized port construction cost budget price information is collected, and then the budget item rate conditions supported by BIM technology is combined to calculate the budget control weight of port construction cost required for practical processing, the construction of the BIM technology-based port construction cost budget control method is completed. The experimental results show that after applying the engineering cost budget control method, the related attributes between the various budget control indicators in the port operation area of Z province have become clear, and the overall cost control effect is gradually approaching the ideal level.
Vitamin B6 Is Under a Tight Balance During Disease Development by Rhizoctonia solani on Different Cultivars of Potato and on Arabidopsis thaliana Mutants

Vitamin B6 is well recognized as an essential antioxidant and plays a role in stress responses. Co-expression of plant and pathogen-derived vitamin B6 genes is critical during disease development of R. solani. However, little is known about the functionality of vitamin B6 vitamers during plant-R. solani interactions and their involvement in disease tolerance. Here, we explored the possible involvement of vitamin B6 during disease progression of potato cultivars of different susceptibility levels to R. solani. A distinct pattern of gene expression, pyridoxine (PN) concentration, and fungal biomass was found in the susceptible cv. Russet Burbank and tolerant cv. Chieftain. Accumulation of reactive oxygen species (ROS) in R. solani mycelia or plant tissues applying non-fluorescence or fluorescence methods was related to up-regulation in the vitamin B6 pathway and is indicative of oxidative stress. Russet Burbank was susceptible to R. solani, which was linked to reduced amounts of VB6 content. Prior to infection, constitutive PN levels were significantly higher in Russet Burbank by 1.6-fold compared to Chieftain. Upon infection with R. solani, PN levels in infected tissues increased more in Chieftain (1.7-fold) compared to Russet Burbank (1.4-fold). R. solani AG3 infection of potato sprouts in both cultivars significantly activates the fungal and plant vitamin B6 and glutathione-S-transferase (GST) genes in a tissue-specific response. Significant fold increases of transcript abundance of the fungal genes ranged from a minimum of 3.60 (RsolSG3GST) to a maximum of 13.91 (RsolAG3PDX2) in the surrounding necrotic lesion tissues (zone 1). On the other hand, PCA showed that the top plant genes STGST and STPDX1.1 were linked to both tissues of necrotic lesions (zone 2) and their surrounding areas of necrotic lesions. Functional characterization of Arabidopsis pdx1.3 mutants challenged with R. solani provided evidence into the role of the vitamin B6 pathway in the maintenance of plant tolerance during disease progression. Overall, we demonstrate that the production of vitamin VB6 is under tight control and is an essential determinant of disease development during the interaction of R. solani with potato cultivars.
Assessment of Mechanical and Tribological Properties of Diamond-Like Carbon Coatings on the Ti13Nb13Zr Alloy

Abstract The paper presents the results of tests on the geometric structure of the surface, hardness and tribological tests of coatings produced by the method of physical vapor deposition (PVD) on the Ti13Nb13Zr alloy. Hardness was determined using MCT3 from Anton Paar, by instrumental indentation. A diamond indenter with Berkovich geometry was used for the measurement.Model tribological tests were carried out in reciprocating motion under conditions of technically dry friction, friction with lubrication of synovial fluid and Ringer’s solution. The counter-sample in the tested friction nodes was a ball of Al2O3 with a diameter of 6 mm. Nanometer hardness measurements showed that as a result of the diamond-like carbon coating (DLC), the hardness increased by an 7-fold. The lowest friction coefficients among all tested friction nodes were obtained for the material combination Ti13Nb13Zr a-C:H - Al2O3 regardless of the conditions of testing. In the case of technically dry friction, the coefficient of friction decreased by 80%, synovial fluid by 70%, and in the case of Ringer’s solution by 88% compared to the results obtained for Ti13Nb13Zr.
The Glutamate System as a Crucial Regulator of CNS Toxicity and Survival of HIV Reservoirs

Glutamate (Glu) is the most abundant excitatory neurotransmitter in the central nervous system (CNS). HIV-1 and viral proteins compromise glutamate synaptic transmission, resulting in poor cell-to-cell signaling and bystander toxicity. In this study, we identified that myeloid HIV-1-brain reservoirs survive in Glu and glutamine (Gln) as a major source of energy. Thus, we found a link between synaptic compromise, metabolomics of viral reservoirs, and viral persistence. In the current manuscript we will discuss all these interactions and the potential to achieve eradication and cure using this unique metabolic profile.
Switching factor products: nurses’ experience with NovoEight

Abstract Haemophilia nurses in the UK are instrumental in supporting people with haemophilia in self-management, including managing treatment options, recording treatment use and understanding the budgetary impact of prescribing practice. The widespread use of prophylaxis identified haemophilia as a high cost disorder to treat, resulting in a financially successful national tendering process with increased scrutiny of clotting factor use at both individual and haemophilia treatment centre level. The UK tenders, undertaken at a national level every three years, have ensured access to current and new therapies at the most cost-effective price through economies of scale in committing to purchase large volumes from suppliers. In the 2018 tendering round, NovoEight® (NovoNordisk) was added to the prescribing list and other recombinant factors were withdrawn, resulting in changes in prescribing for individual people with haemophilia. This ‘switching’ process is not uncommon in the UK, where national tenders have been in place since 2004. However, the unseen additional workload for nurses, driven by the demands of timely switching to meet product volumes and contracts, has never been captured. During the 2018 switch we interviewed 11 nurses and one operational manager from haemophilia centres across the UK to identify the barriers and facilitators to instigating this change. Ultimately the switching was completed in a timely manner, demonstrating significant cost reductions for factor concentrates. The unseen workload of the nurse – identifying which patients should have their product switched, discussion with and education of patients/families, adjusting prescriptions for home delivery of clotting factor concentrates and stock management and control to avoid waste, and organising the necessary additional clinic visits – was identified and costed based on salary per hour. Nurses remained positive that they were able to undertake this additional role but recognised that, with no specific national guidance regarding product choice, there may have inevitably been differences in approach between treatment centres.
Diurnal variation of denitrification and nitrification in sediments colonized by benthic microphytes

Diurnal variation of denitrification in sediments with benthic microphytes was investigated by a 15N isotope-pairing technique in order to distinguish between coupled nitrification-denitrification and denitrification of nitrate supplied from the water column. Sediments were incubated in a continuous flowthrough system and exposed to diurnal light and dark cycles. Illumination of both limnetic and estuarine sediments doubled the rate of coupled nitrification-denitrification but reduced the rate of denitrification of nitrate supplied from the water column by -50%. Photosynthesis in the uppermost sediment layers during illumination led to deeper oxygen penetration and a resultant stimulation of nitrification. This stimulation may explain the increased rate of coupled nitrification-denitrification during illumination. The rate of denitrification of nitrate supplied from the water column was reduced during illumination due to a longer diffusion path between water and the anoxic denitrification zone. Denitrification, the bacterial reduction of nitrate to nitrogen gas via nitrite, is an important nitrogen sink in aquatic environments. There are two main sources of nitrate for sediment denitrification: nitrate diffusing into the sediment from the water column and nitrate produced by nitrification in the sediment (Jenkins and Kemp 1984; Seitzinger 1988). The processes of nitrification and denitrification are usually vertically separated within the sediment (Vanderborght and Billen 1975). Nitrification is strictly aerobic and therefore restricted to a thin oxic zone in the upper few millimeters of the sediment. Denitrification takes place in anoxic environments, and in many sediments, most activity is found just below the oxic-anoxic interface (Sweerts and de Beer 1989). The rates of nitrification and denitrification in the active microenvironments are controlled by the availability of substrates, which to a large extent are supplied by diffusion along
Conservation genetics of the endangered eastern freshwater cod, Maccullochella ikei

Fragmentation over evolutionary time scales following vicariant and dispersal events has long been recognised as a dominant process in biological diversification and speciation; while anthropogenic habitat fragmentation in recent times is considered a threat to the long-term persistence of species and ecosystems. The eastern freshwater cod Maccullochella ikei is Australia’s largest endangered freshwater fish species. Abundant in the Clarence and Richmond River systems at the time of European settlement, populations crashed in the early 1900s causing local extinctions and range reduction. Recovery efforts, including a prohibition on fishing for M. ikei and hatchery breeding programs, were initiated in an attempt to re-establish locally extirpated populations and to support the remnant population. This thesis aims to fill critical gaps in the knowledge of M. ikei by examining genetic diversity over a broad range of evolutionary scales. Microsatellite and mitochondrial markers and a DNA extraction method were developed and applied to address issues of conservation concern including taxonomy, hybridisation, genetic variation, population structure, effective population size and genetic stocking impact. Mitochondrial sequence and nuclear genotypic data were used to infer the evolutionary relationships among the Murray cod Maccullochella peelii peelii from the inland Murray-Darling Basin and taxa from eastern coastal drainages, M. ikei and Mary River cod M. peelii mariensis. Phylogenetic analyses provide strong support for a more recent common ancestry between M. ikei and M. p. mariensis. This finding conflicts with the existing taxonomy and suggests that ancestral cod crossed the Great Dividing Range around 1 million years ago and subsequently colonised east coast drainages during Pleistocene glacial periods. The eastern taxa, persisting in isolated drainages at the periphery of the historical coastal distribution of Maccullochella are estimated to have diverged around 300 thousand years ago. Mary River cod are morphologically and genetically distinct and may warrant recognition as a separate species. High levels of population structure (global FST = 0.13) and a pattern of isolation by distance in M. ikei from the Clarence system are indicative of fragmentation and restricted dispersal. Genetically-distinct upstream populations are small and isolated with effective population sizes below 30. Cluster analysis and assignment tests suggest that gene flow to and among these populations is limited. Bayesian and frequency-based analysis of hatchery progeny suggest population admixture in the hatchery, with most parental stock sourced from upstream sites with reduced genetic variation. Analysis of temporal samples from the largest remnant population showed a significant loss in genetic variation (>20%) since the commencement of stocking, consistent with genetic swamping with hatchery-bred fish. These findings are relevant to the conservation of M. ikei and to captive breeding programs generally as they show that genetic…
Genetic Animal Models for Arrhythmogenic Cardiomyopathy

Arrhythmogenic cardiomyopathy has been clinically defined since the 1980s and causes right or biventricular cardiomyopathy associated with ventricular arrhythmia. Although it is a rare cardiac disease, it is responsible for a significant proportion of sudden cardiac deaths, especially in athletes. The majority of patients with arrhythmogenic cardiomyopathy carry one or more genetic variants in desmosomal genes. In the 1990s, several knockout mouse models of genes encoding for desmosomal proteins involved in cell–cell adhesion revealed for the first time embryonic lethality due to cardiac defects. Influenced by these initial discoveries in mice, arrhythmogenic cardiomyopathy received an increasing interest in human cardiovascular genetics, leading to the discovery of mutations initially in desmosomal genes and later on in more than 25 different genes. Of note, even in the clinic, routine genetic diagnostics are important for risk prediction of patients and their relatives with arrhythmogenic cardiomyopathy. Based on improvements in genetic animal engineering, different transgenic, knock-in, or cardiac-specific knockout animal models for desmosomal and nondesmosomal proteins have been generated, leading to important discoveries in this field. Here, we present an overview about the existing animal models of arrhythmogenic cardiomyopathy with a focus on the underlying pathomechanism and its importance for understanding of this disease. Prospectively, novel mechanistic insights gained from the whole animal, organ, tissue, cellular, and molecular levels will lead to the development of efficient personalized therapies for treatment of arrhythmogenic cardiomyopathy.