Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional Pathway Identification with CRISPR/Cas9 Genome Wide Gene Disruption in Human Dopaminergic Neuronal Cells Following Chronic Treatment with Dieldrin.

Organochlorine pesticides, once widely used, are extremely persistent and bio-accumulative in the environment. Epidemiological studies have implicated that environmental exposure to organochlorine pesticides including dieldrin is a risk factor for the development of Parkinson's disease. However, the pertinent mechanisms of action remain poorly understood. In this study, we carried out a genome wide (Brunello library, 19,114 genes, 76,411 sgRNA) CRISPR/Cas9 screen in human dopaminergic SH-SY5Y neuronal cells exposed to a chronic treatment (30 days) with dieldrin to identify cellular pathways that are functionally related to the chronic cellular toxicity. Our results indicate that dieldrin toxicity was enhanced by gene disruption of specific components of the ubiquitin proteasome system as well as, surprisingly, the protein degradation pathways previously implicated in inherited forms of Parkinson's disease, centered on parkin. Additionally, disruption of regulatory components of the mTOR pathway which integrates cellular responses to both intracellular and extracellular signals and is a central regulator for cell metabolism, growth, proliferation and survival, led to increased sensitivity to dieldrin-induced cellular toxicity. This study is one of the first to apply a genome wide CRISPR/Cas9-based functional gene disruption screening approach in an adherent neuronal cell line to globally decipher cellular mechanisms that contribute to environmental toxicant-induced neurotoxicity and provides novel insight into the dopaminergic neurotoxicity associated with chronic exposure to dieldrin.
Aortic Hemodynamics and Cognitive Performance in Postmenopausal Women: Impact of Pregnancy History

Abstract BACKGROUND Studies demonstrate an association between aortic hemodynamics and cognitive function. The impact of pregnancy history on this association is unknown. METHODS Postmenopausal women (age 59 ± 5 years; years since last pregnancy 35 ± 3) with either a history of preeclampsia (PE; n = 34) or a history of a normotensive pregnancy (NP; n = 30) underwent cognitive testing: Letter-Number Sequencing, Digit Span, Trail Making Test, and letter and category fluency. Applanation tonometry was used to derive aortic systolic and diastolic blood pressure and augmentation index. RESULTS Distribution of cognitive scores and aortic hemodynamic measures was similar between the PE and NP groups. Principal component (PC) analysis was used to reduce the 3 aortic hemodynamic measures and the 5 cognitive variables to single summary indices, each representing a weighted average of their respective constituent variables. Using a multivariable linear model based on these PCs that adjusted for pregnancy history and body mass index, the composite index of aortic hemodynamics was associated with the summary cognitive index, whether taking into account a potential interaction with pregnancy history (P = 0.035) or not (P = 0.026) (interaction P = 0.178). Multivariable modeling of individual cognitive tests revealed a differential association for letter fluency by pregnancy history (test for interaction P = 0.023); this score correlated with the aortic hemodynamic index in the PE (partial R2 = 0.20), but not the NP (partial R2 = 0.00) group. CONCLUSIONS Elevated aortic hemodynamics may negatively impact cognitive function in postmenopausal women with specific executive functions, such as letter fluency, being impacted more by a pregnancy history of PE.
Magnetically Responsive Peptide Coacervates for Dual Hyperthermia and Chemotherapy Treatments of Liver Cancer

Liver cancer is an aggressive malignancy associated with high levels of mortality and morbidity. Doxorubicin (Dox) is often used to slow down liver cancer progression; however its efficacy is limited, and its severe side effects prevent its routine use at therapeutic concentrations. We present a biomimetic peptide that coacervates into micro-droplets, within which both Dox and magnetic nanoparticles (MNPs) can be sequestered. These Dox-loaded Magnetic Coacervates (DMCs) can be used for thermo-chemotherapy, with the controlled release of Dox triggered by an external Alternating Magnetic Field (AMF). The DMCs are internalized by the cells via an energy-independent mechanism which is not based on endocytosis. Application of AMF generates a temperature of 45°C within the DMCs, triggering their disassembly and the simultaneous release of Dox, thereby resulting in dual hyperthermia and chemotherapy for more efficient cancer therapy. In vitro studies conducted under AMF reveal that DMCs are cytocompatible and effective in inducing HepG2 liver cancer cell death. Thermo-chemotherapy treatment against HepG2 cells is also shown to be more effective compared to either hyperthermia or chemotherapy treatments alone. Thus, our novel peptide DMCs can open avenues in theranostic strategies against liver cancer through programmable, wireless, and remote control of Dox release.
ToxicoDB: an integrated database to mine and visualize large-scale toxicogenomic datasets

Abstract In the past few decades, major initiatives have been launched around the world to address chemical safety testing. These efforts aim to innovate and improve the efficacy of existing methods with the long-term goal of developing new risk assessment paradigms. The transcriptomic and toxicological profiling of mammalian cells has resulted in the creation of multiple toxicogenomic datasets and corresponding tools for analysis. To enable easy access and analysis of these valuable toxicogenomic data, we have developed ToxicoDB (toxicodb.ca), a free and open cloud-based platform integrating data from large in vitro toxicogenomic studies, including gene expression profiles of primary human and rat hepatocytes treated with 231 potential toxicants. To efficiently mine these complex toxicogenomic data, ToxicoDB provides users with harmonized chemical annotations, time- and dose-dependent plots of compounds across datasets, as well as the toxicity-related pathway analysis. The data in ToxicoDB have been generated using our open-source R package, ToxicoGx (github.com/bhklab/ToxicoGx). Altogether, ToxicoDB provides a streamlined process for mining highly organized, curated, and accessible toxicogenomic data that can be ultimately applied to preclinical toxicity studies and further our understanding of adverse outcomes.
Construction and Performance of a Temperature-Gradient Bar and Chamber.

An inexpensive temperature-gradient bar and chamber for use in studies of seed germination and root growth is described. Aluminum troughs and a bar, surrounded by insulation and heated and cooled at their ends by water baths, form the floor of a chamber. A plexiglass top permits illumination by overhead light banks. The temperature gradient may be adjusted to any range within the limits of 10° and 50°C. The linearity and stability of the bar gradient, and the presence of temperature and humidity gradients in the chamber air above the bar, are discussed.
Real Time Monitoring of Calcium Oxalate Precipitation Reaction by Using Corrosion Resistant Magnetoelastic Resonance Sensors

The magnetoelastic resonance is used to monitor the precipitation reaction of calcium oxalate (CaC2O4) crystals in real-time, by measuring the shift of the resonance frequency caused by the mass increase on the resonator. With respect to previous work on the same matter, the novelty lies in the adoption of an amorphous ferromagnetic alloy, of composition Fe73Cr5Si10B12, as resonator, that replaces the commercial Metglas® 2826 alloy (composition Fe40Ni38Mo4B18). The enhanced corrosion resistance of this material allows it to be used in biological environments without any pre-treatment of its surface. Additionally, the measurement method, which has been specifically adapted to this application, allows quick registration of the whole resonance curve as a function of the excitation frequency, and thus enhances the resolution and decreases the detection noise. The frequency shift is calibrated by the static deposition of well-known masses of CaC2O4. The resonator dimensions have been selected to improve sensitivity. A 20 mm long, 2 mm wide and 25 μm thick magnetoelastic resonator has been used to monitor the precipitation reaction of calcium oxalate in a 500 s time interval. The results of the detected precipitated mass when oxalic acid and calcium chloride are mixed in different concentrations (30 mM, 50 mM and 100 mM) are presented as a function of time. The results show that the sensor is capable of monitoring the precipitation reaction. The mass sensitivity obtained, and the corrosion resistance of the material, suggest that this material can perform excellently in monitoring this type of reaction.
Review of Sexual Selection and Chemical Communication in the Lobster, Homarus americanus

Field and laboratory observations have shown that female lobsters, Homarus americanus, are the active searching partner in courtship, choosing locally dominant males. The attractive features of the male are suspected to be intrasexual aggressive behavior and chemical cues. Size-based dominance is an important factor allowing males to secure a suitable mating shelter. In nature, male and female lobsters often approach and check shelters of other lobsters. This behavior may allow the animals to monitor the observed daily and seasonal changes in their physical and social environment. Premolt females approach the dominant male's shelter frequently in the weeks before the female's molt. Indirect evidence indicates that the female then "blows" a urine-related sex pheromone into the male shelter. One to several days before molting, a female enters the male shelter. Female intrasexual competition increases the premolt, but not the postmolt, cohabitation period. During cohabitation, males fan with their pleopods b.
Seasonal variability in the gut ultrastructure of the parasitic copepod Neoergasilus japonicus (Copepoda, Poecilostomatoida)

The gut structure and ultrastructure of Neoergasilus japonicus (Harada, 1930), a copepod from the family Ergasilidae (Copepoda, Poecilostomatoida) and a parasite of fish, were compared at different periods of the life cycle: in free-living specimens in October and after attaching to fish in January and June. Differences in the depth of the intestinal epithelium were prominent and other cellular characteristics appeared seasonally variable. We relate these to changes in the physiological activity. Preliminary data from stable-isotope analyses of attached specimens suggest nutritional contribution from parasitism. The possibility of a diapause in the life cycle, as well as the relationship between the morphology of the gut and early evolutionary parasitism of N. japonicus, are discussed.
Acute Effects of Butyrate on Induced Hyperpermeability and Tight Junction Protein Expression in Human Colonic Tissues

Intact intestinal barrier function is essential for maintaining intestinal homeostasis. A dysfunctional intestinal barrier can lead to local and systemic inflammation through translocation of luminal antigens and has been associated with a range of health disorders. Butyrate, a short-chain fatty acid derived from microbial fermentation of dietary fibers in the colon, has been described as an intestinal barrier-strengthening agent, although mainly by using in vitro and animal models. This study aimed to investigate butyrate’s ability to prevent intestinal hyperpermeability, induced by the mast cell degranulator Compound 48/80 (C48/80), in human colonic tissues. Colonic biopsies were collected from 16 healthy subjects and intestinal permeability was assessed by Ussing chamber experiments. Furthermore, the expression levels of tight junction-related proteins were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Pre-treatment with 5 mM butyrate or 25 mM butyrate did not protect the colonic tissue against induced paracellular or transcellular hyperpermeability, measured by FITC-dextran and horseradish peroxidase passage, respectively. Biopsies treated with 25 mM butyrate prior to stimulation with C48/80 showed a reduced expression of claudin 1. In conclusion, this translational ex vivo study did not demonstrate an acute protective effect of butyrate against a chemical insult to the intestinal barrier in healthy humans.
Genome-wide association study of partial resistance to sclerotinia stem rot of cultivated soybean based on the detached leaf method

Sclerotinia stem rot (SSR) is a devastating fungal disease that causes severe yield losses of soybean worldwide. In the present study, a representative population of 185 soybean accessions was selected and utilized to identify the quantitative trait nucleotide (QTN) of partial resistance to soybean SSR via a genome-wide association study (GWAS). A total of 22,048 single-nucleotide polymorphisms (SNPs) with minor allele frequencies (MAF) > 5% and missing data < 3% were used to assess linkage disequilibrium (LD) levels. Association signals associated with SSR partial resistance were identified by two models, including compressed mixed linear model (CMLM) and multi-locus random-SNP-effect mixed linear model (mrMLM). Finally, seven QTNs with major effects (a known locus and six novel loci) via CMLM and nine novel QTNs with minor effects via mrMLM were detected in relation to partial resistance to SSR, respectively. One of all the novel loci (Gm05:14834789 on Chr.05), which was co-located by these two methods, might be a stable one that showed high significance in SSR partial resistance. Additionally, a total of 71 major and 85 minor candidate genes located in the 200-kb genomic region of each peak SNP detected by CMLM and mrMLM were found, respectively. By using a gene-based association, a total of six SNPs from three major effects genes and eight SNPs from four minor effects genes were identified. Of them, Glyma.18G012200 has been characterized as a significant element in controlling fungal disease in plants.
Divergence among arctic and alpine populations of the annual, Koenigia islandica: morphology, life-history, and phenology.

Arctic and alpine habitats occur along complex environmental gradients, and over an extensive geographical range. Despite some selective forces common to these habitats, evolutionary divergence among populations of arctic and alpine plants along this gradient is expected. Of particular significance, both in the context of life-history theory and for implications of climate change, are the few annual species that have adapted to the constraints of an unpredictable, short growing season. In this study, morphological, life-history and phenological characters were found to differ significantly among six widely distributed populations of the arctic-alpine annual Koenigia islandica. On the basis of morphology and life-history traits, populations from high latitudes, with the exception of Svalbard, performed better in simulated arctic conditions, whereas the low latitude alpine plants from Colorado showed enhanced performance under simulated alpine conditions. On the basis of phenology, the six populations can be clearly grouped into arctic, high latitude alpine and alpine populations: arctic plants were found to develop and flower earliest; alpine plants latest. Because these results were obtained using seeds harvested from plants first grown through a complete generation in growth chambers, they indicate strong genetic differentiation. We discuss possible adaptive explanations for observed differences among the six geographically divergent populations.
Mathematical modeling and an application of the filled function method in entomology

Macrosiphum rosae (L.) is one of the most destructive pests for Rosa damascena (Miller) when it is found in high numbers. In order to understand the population dynamics of this pest, our priority should be the determination of what extent environmental factors affect the pest population. In this study, we apply fuzzy logic modeling to visualize the population variations, which depends on the environmental factors (temperature and humidity), by using the data obtained from the field studies. After that, we determine the values of temperature and humidity that makes the number of M. rosae maximum by using the filled function method as a global optimization technique.
The dynamics of aquatic systems. 2. The effects of nutrient enrichment on model plankton communities1,2

When results of laboratory experiments on the effects of nutrient enrichment of algal cultures are extrapolated to field conditions, the predictions of the experiments arc seldom fulfilled, because the behavior of a species in a network of interacting variables in nature is quite different from its behavior under controlled conditions. The method of loop analysis is used to demonstrate the propertics of a set of models containing three kinds of algae and three kinds of nutrients. Many unexpected effects develop from the interactions within the network, and one-link physiological effects cannot be cxtrapolatcd to ecological situations. For these situations, it is recommended that Licbig’s law of the minimulii be replaced by a more holistic approach. Since Liebig (1840) first proposed the law of the minimum with its subsequent extension into the limiting factor concept by Blackman (1905) and the law of tolerancc by Shelford ( 1911), there has been little theoretical development of the basic concept despite its pivotal position in ecology ( Browne 1942). The law of the minimum essentially stated that among all factors that arc required for the growth and maintenance of a population, the single requircment which is in shortest supply will have the greatest, if not exclusive, effect on the growth of that population. The limiting factor concept did not claim that the same factor would always be limiting to a particular species but rather that as a limiting factor was added, the growth response of a population would level off at a higher asymptotic value. The overall approach was designed to reduce complexity by defining, at the physiological level, one determining factor of an isolated population
Study on statics and fatigue analysis of dental implants in the descending process of alveolar bone level

Alveolar bone atrophy can directly cause a decrease in bone level. The effect of this process on the service life of dental implants is unknown. The aim of this study was to determine the failure forms of the two-piece dental implants in the descending process of alveolar bone level, and the specific states of the components during the failure process. The CAD software SolidWorks was used to establish the model of alveolar bone and dental implants in this article. The finite element analysis was used to analyze the statics of the dental implants in the host oral model. The finite element analysis results showed that the stress concentration point of the implant and abutment in the implant system has changed greatly during the descending process of alveolar bone level, and indirectly increased the fatigue life of the same fatigue risk point. At the same time, the dental implants were tested in vitro in the descending process of alveolar bone level. Then, the fracture of the implant system was scanned by scanning electron microscope. The fatigue test results proved the finite element analysis hypothesis the central screw first fractured under fatigue and then caused an overload break of the implant and abutment.
Infrared Small Target Detection via Non-Convex Tensor Rank Surrogate Joint Local Contrast Energy

Small target detection is a crucial technique that restricts the performance of many infrared imaging systems. In this paper, a novel detection model of infrared small target via non-convex tensor rank surrogate joint local contrast energy (NTRS) is proposed. To improve the latest infrared patch-tensor (IPT) model, a non-convex tensor rank surrogate merging tensor nuclear norm (TNN) and the Laplace function, is utilized for low rank background patch-tensor constraint, which has a useful property of adaptively allocating weight for every singular value and can better approximate l 0 -norm. Considering that the local prior map can be equivalent to the saliency map, we introduce a local contrast energy feature into IPT detection framework to weight target tensor, which can efficiently suppress the background and preserve the target simultaneously. Besides, to remove the structured edges more thoroughly, we suggest an additional structured sparse regularization term using the l 1 , 1 , 2 -norm of third-order tensor. To solve the proposed model, a high-efficiency optimization way based on alternating direction method of multipliers with the fast computing of tensor singular value decomposition is designed. Finally, an adaptive threshold is utilized to extract real targets of the reconstructed target image. A series of experimental results show that the proposed method has robust detection performance and outperforms the other advanced methods.
Synergistic activities of ceftazidime-avibactam in combination with different antibiotics against colistin-nonsusceptible clinical strains of Pseudomonas aeruginosa

Abstract Background: This study aims to analyse the effect of ceftazidime-avibactam plus various antibiotics against multidrug-resistant (MDR) Pseudomonas aeruginosa isolated from Intensive Care Units. Methods: 40 non-duplicate P. aeruginosa isolates were screened for their MICs of ceftazidime, ceftazidime-avibactam, colistin, levofloxacin, doripenem and tobramycin. MICs were determined by the broth microdilution method. The in vitro bactericidal activities of ceftazidime-avibactam compared to studied antibiotics were also determined by time-kill curve assays both at 1xMIC and at 4xMIC against carbapenemase-producing or -not producing six colistin-nonsusceptible MDR clinical strains of P. aeruginosa. Additionally, synergistic interactions were investigated by the time-kill curve assay. Results: The MIC90 values for ceftazidime, ceftazidime-avibactam, colistin, levofloxacin, doripenem and tobramycin against MDR P. aeruginosa isolates were found to be >256, 64, 8, 64, 128, and >256 mg/L, respectively. The minimum bactericidal concentration90 values for those antibiotics were also >256, 64, 16, 128, 256, and >256 mg/L, respectively. While doripenem, tobramycin and levofloxacin were bactericidal (>3 log10 killing) against the 2/6, 3/6 and 1/6 P. aeruginosa isolates at 4xMIC concentrations, respectively, levofloxacin and tobramycin were bactericidal against only one isolate (1/6) at 1xMIC concentrations at 24 h. The synergistic interactions of these antimicrobial agents were also achieved with ceftazidime/avibactam + colistin (4/6), ceftazidime/avibactam + tobramycin (3/6), and ceftazidime/avibactam + levofloxacin (3/6) combinations. No antagonism was observed against studied P. aeruginosa strains. Conclusions: The findings of this study suggest that ceftazidime/avibactam with colistin, or tobramycin, were effective against colistin-nonsusceptible strains. This combination therapy could be an alternative antibiotic therapy for resistant P. aeruginosa strains.