Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of gut microbiota on in vivo metabolism and tissue accumulation of cytochrome P450 3A metabolized drug: Midazolam

Abstract The link between drug‐metabolizing enzymes and gut microbiota is well established. In particular, hepatic cytochrome P450 (CYP) 3A activities are presumed to be affected by gut microbiota. However, there is no direct evidence that the gut microbiota affects CYP3A metabolism or the clearance of clinically relevant drugs in vivo. Our purpose was to evaluate the effects of gut microbiota on in vitro and in vivo drug metabolism and on the clearance of midazolam, which is a standard CYP3A metabolized drug. Hepatic Cyp3a activity and in vitro midazolam hydroxylase activity were compared using specific pathogen‐free (SPF) and germ‐free (GF) mice. In a pharmacokinetics (PK) study, SPF and GF mice were intraperitoneally injected with 60 mg/kg of midazolam, and plasma and tissue concentrations were measured. Hepatic Cyp3a activity and midazolam hydroxylase activity were significantly lower in GF mice than in SPF mice. Notably, in the PK study, the area under the plasma concentration–time curve from time zero to infinity and the elimination half‐life were approximately four‐fold higher in GF mice compared with SPF mice. Furthermore, the concentration of midazolam in the brain 180 min after administration was about 14‐fold higher in GF mice compared with SPF mice. Together, our results demonstrated that the gut microbiota altered the metabolic ability of Cyp3a and the tissue accumulation of midazolam.
Nibbling Frequency of Carps in Periphyton-Based Aquaculture Systems with and without Supplemental Feed

The nibbling frequency of five carp species (rohu Labeo rohita, mrigal Cirrhinus mrigala, catla Catla catla, common carp Cyprinus carpio, silver carp Hypophthalmichthys molitrix) on bamboo lateral sticks (kanchi) colonized by periphyton was examined in fed and unfed systems. There were three treatments: (a) no carp and no supplemental feed (control), (b) carp without supplemental feeding (unfed treatment), and (c) carp with supplemental feeding (fed treatment). For 12 h (07:30-19:30) during six days, nibbling behavior was observed in real time via a digital video camera and recorded on a camcorder for later viewing. Rohu, catla, and common carp nibbled on the kanchi, while mrigal and silver carp did not. In rohu and catla, the nibbling frequency was significantly higher in the unfed treatment than in the fed treatment (p<0.05); supplemental feeding reduced nibbling frequency by 81% and 91%, respectively. Hence, in periphyton-based aquaculture systems, there is no need for a high density of substrates in ponds that receive supplemental feed. Alternatively, the amount of supplied feed can be reduced to force these species to consume more periphyton.
Hierarchical Doped Gelatin-Derived Carbon Aerogels: Three Levels of Porosity for Advanced Supercapacitors

Nitrogen-doped graphene-based aerogels with three levels of hierarchically organized pores were prepared via a simple environmentally friendly process, and successfully tested in supercapacitor applications. Mesopores and macropores were formed during the aerogel preparation followed by carbonization and its chemical activation by potassium hydroxide (KOH). These mesopores and macropores consist of amorphous carbon and a 3D graphene framework. Thermal treatment at 700 °C, 800 °C, 900 °C in N2 atmosphere was done to etch out the amorphous carbon and obtain a stable N-doped 3D graphene. Specific capacitance values obtained from the electrochemical measurements are in the range of 232–170 F× g−1. The thus fabricated structures showed excellent cyclic stability, suggesting that these materials have potential as electrodes for solid asymmetric supercapacitors.
The Long Noncoding RNA NEAT1 Promotes Sarcoma Metastasis by Regulating RNA Splicing Pathways

Soft-tissue sarcomas (STS) are rare malignancies showing lineage differentiation toward diverse mesenchymal tissues. Half of all high-grade STSs develop lung metastasis with a median survival of 15 months. Here, we used a genetically engineered mouse model that mimics undifferentiated pleomorphic sarcoma (UPS) to study the molecular mechanisms driving metastasis. High-grade sarcomas were generated with Cre recombinase technology using mice with conditional mutations in Kras and Trp53 (KP) genes. After amputation of the limb bearing the primary tumor, mice were followed for the development of lung metastasis. Using RNA-sequencing of matched primary KP tumors and lung metastases, we found that the long noncoding RNA (lncRNA) Nuclear Enriched Abundant Transcript 1 (Neat1) is significantly upregulated in lung metastases. Furthermore, NEAT1 RNA ISH of human UPS showed that NEAT1 is upregulated within a subset of lung metastases compared with paired primary UPS. Remarkably, CRISPR/Cas9-mediated knockout of Neat1 suppressed the ability of KP tumor cells to colonize the lungs. To gain insight into the underlying mechanisms by which the lncRNA Neat1 promotes sarcoma metastasis, we pulled down Neat1 RNA and used mass spectrometry to identify interacting proteins. Interestingly, most Neat1 interacting proteins are involved in RNA splicing regulation. In particular, KH-Type Splicing Regulatory Protein (KHSRP) interacts with Neat1 and is associated with poor prognosis of human STS. Moreover, depletion of KHSRP suppressed the ability of KP tumor cells to colonize the lungs. Collectively, these results suggest that Neat1 and its interacting proteins, which regulate RNA splicing, are involved in mediating sarcoma metastasis. Implications: Understanding that lncRNA NEAT1 promotes sarcoma metastasis, at least in part, through interacting with the RNA splicing regulator KHSRP may translate into new therapeutic approaches for sarcoma.
Experimental demonstration of the energetic cost of parasitism in free-ranging hosts

Although some parasites have obvious pathogenic effects, others appear to have subtle, indirect effects that are poorly understood, particularly in natural populations. Indirect effects may result from parasites altering host metabolic rate and hence host energy needs, yet no experimental studies have shown this to be the case for non-laboratory hosts. We report the results of a long-term field experiment designed to test the impact of parasites on host energetics. We measured the energetics of feral rock doves ( with populations of feather-feeding lice, traditionally considered to have little or no effect on host fitness. The lice reduced feather mass leading to increased thermal conductance and metabolic rate, as well as a steady reduction in host body mass over the course of the nine-month study. Our results demonstrate that even classically ‘benign’ parasites such as feather lice can reduce host condition through the accumulation of subtle energetic costs over time. We argue that experimental manipulations are a prerequisite for documenting such effects.
A Dynamic Hanging-Drop System for Mesenchymal Stem Cell Culture

There have been many microfluid technologies combined with hanging-drop for cell culture gotten developed in the past decade. A common problem within these devices is that the cell suspension introduced at the central inlet could cause a number of cells in each microwell to not regularize. Also, the instability of droplets during the spheroid formation remains an unsolved ordeal. In this study, we designed a microfluidic-based hanging-drop culture system with the design of taper-tube that can increase the stability of droplets while enhancing the rate of liquid exchange. A ring is surrounding the taper-tube. The ring can hold the cells to enable us to seed an adequate amount of cells before perfusion. Moreover, during the period of cell culture, the mechanical force around the cell is relatively low to prevent stem cells from differentiate and maintain the phenotype. As a result of our hanging system design, cells are designed to accumulate at the bottom of the droplet. This method enhances convenience for observation activities and analysis of experiments. Thus, this microfluid chip can be used as an in vitro platform representing in vivo physiological conditions, and can be useful in regenerative therapy.
Agent-based double auction algorithm for global supply chain system

The market mechanism based on a general equilibrium theory in economics solves distributed resource allocation problems by allocating the scheduled resources according to market prices. We propose an agent-based double auction algorithm and demonstrate the applicability of economic analysis to this framework. The product allocation problem in a supply chain is dealt with in detail, as a case study to validate our idea. The proposed algorithm is proved to emerge sophisticated product flows in a supply chain and conduct a Pareto optimal solution on multi-objective problems.
CONSERVED PROPERTIES OF ENZYMATIC SYSTEMS: PRENYLTRANSFERASE KINETICS

SUMMARY Motivation: Prenyltransferase is a key enzyme of the biosynthesis of isoprenoids. Closer examination of the kinetic properties of prenyltransferase, development of mathematical models of its regulatory activity would broaden our understanding of the properties of the molecular systems that control the synthesis of sterols, sesquiterpenes, dolichols, ubiquinones and carotenoids, and also farnesylation and geranylgeranylation of proteins. Results: A computer-aided mathematical model that describes the steady-state rate of the enzymatic reaction of farnesyl diphoshate synthesis was developed. Optimum parameter values were chosen using data that describes the function of human prenyltransferase. It was demonstrated that the function of chicken prenyltransferase can be described using the same proposed model.
Future Climate Significantly Alters Fungal Plant Pathogen Dynamics during the Early Phase of Wheat Litter Decomposition

Returning wheat residues to the soil is a common practice in modern agricultural systems and is considered to be a sustainable practice. However, the negative contribution of these residues in the form of “residue-borne pathogens” is recognized. Here, we aimed to investigate the structure and ecological functions of fungal communities colonizing wheat residues during the early phase of decomposition in a conventional farming system. The experiment was conducted under both ambient conditions and a future climate scenario expected in 50–70 years from now. Using MiSeq Illumina sequencing of the fungal internal transcribed spacer 2 (ITS2), we found that plant pathogenic fungi dominated (~87% of the total sequences) within the wheat residue mycobiome. Destructive wheat fungal pathogens such as Fusarium graminearum, Fusarium tricinctum, and Zymoseptoria tritci were detected under ambient and future climates. Moreover, future climate enhanced the appearance of new plant pathogenic fungi in the plant residues. Our results based on the bromodeoxyuridine (BrdU) immunocapture technique demonstrated that almost all detected pathogens are active at the early stage of decomposition under both climate scenarios. In addition, future climate significantly changed both the richness patterns and the community dynamics of the total, plant pathogenic and saprotrophic fungi in wheat residues as compared with the current ambient climate. We conclude that the return of wheat residues can increase the pathogen load, and therefore have negative consequences for wheat production in the future.
Effects of chronic treatment with new strains of Lactobacillus plantarum on cognitive, anxiety- and depressive-like behaviors in male mice

Psychobiotics correspond to a class of probiotics, mainly of the genus Lactobacillus and Bifidobacterium, capable of producing neuroactive substances, such as γ-aminobutyric acid (GABA) and serotonin, which exert effects on the brain-gut axis. Evidence suggests that psychobiotics can have a beneficial effect on mood, anxiety and cognition. The present study evaluated the effects of chronic administration of two new strains of Lactobacillus plantarum, L. plantarum 286 (Lp 286) and L. plantarum 81 (Lp 81) isolated from the fermentation of cocoa (Theobroma cacao L.) and cupuaçu (Theobroma grandiflorum), respectively, on cognitive, anxiety- and depressive-like behaviors in male Swiss mice. Different groups of animals were administered (oral gavage) solutions of vehicle (0.85% saline plus 15% skim milk), Lp 286 (109/0.1 ml CFU) or Lp 81 (109/0.1 ml CFU) for 30 days, and animals were tested for general locomotor activity, depressive-like behavior in the forced swim test, and learning/memory and anxiety-like behavior in the plus-maze discriminative avoidance task. Treatment with the strains Lp 286 and Lp 81 did not interfere with locomotor activity or learning and memory. The Lp 286 strain exerted anti-depressant- and anxiolytic-like effects under our experimental conditions. Our findings add to the current body of evidence suggesting that probiotics from the genus Lactobacillus may exert psychobiotic potential and introduce a new strain, Lp 286, as a potential candidate in the prevention or as therapeutic adjuvant in the treatment of mental disorders.
Two Endopolygalacturonase Genes in Trichoderma virens: In Silico Characterization and Expression during Interaction with Plants

AbstractThe ability of Trichoderma spp. to antagonize most phytopathogenic fungiand to interact with plants by inducing their resistance and promotingtheir growth has been widely described. Endopolygalacturonases(endoPGs) produced by Trichoderma spp. can assist root penetration andplay a pre-eliciting role in induced systemic resistance (ISR), a beneﬁcialeffect detected in plants colonized by Trichoderma. In this study, twoendoPG genes (Tvpg1 and Tvpg2) have been identiﬁed and partially char-acterized in a T. virens isolate, previously investigated for its antagonisticability in several biological systems. An extensive in silico analysis showedrelatively low sequence similarities (53%) between TvPG1 and TvPG2proteins and underscored interesting phylogenetic relationships in thecomparison of endoPG genes among fungal genomes. The phylogeny ofendoPGs suggests a differentiation in action mechanisms associated withbiological functions as one cluster shows only genes from plant-interact-ing organisms. A gene expression analysis demonstrated a different regu-lation pattern for those genes. The Tvpg1 gene was induced both when thefungus was grown in liquid cultures supplemented with pectin or plantcell walls and when it was applied to tomato roots in a growth chamber.Expression times were comparable in both systems. On the contrary, theTvpg2 gene displayed a constitutive expression in all conditions tested,including controls. The molecular communication between tomato rootsand T. virens was investigated by checking the expression of a tomato PGIP(Lepgip1) in roots colonized by fungal mycelium. The Lepgip1 transcriptwas induced at times coincident with Tvpg1 expression, suggesting a corre-lation between the two gene products. This paper reports the results ofﬁrst investigations of T. virens endoPG genes performed on a structural,phylogenetic and functional level.IntroductionFungi belonging to the genus Trichoderma areubiquitous and typically soilborne micro-organisms(Esposito and Da Silva 1998), which display a consid-erable range of lifestyles that have been recentlyinvestigated by means of genomics (Martinez et al.2008; Druzhinina et al. 2011; Kubicek et al. 2011;Gruber et al. 2013). Trichoderma spp. have beenwidely studied as biocontrol agents of fungal plantpathogens due to the frequent discovery of isolateswith antagonistic abilities against plant-pathogenicfungi (Kubicek et al. 2001; Benitez et al. 2004). Onemeans by which Trichoderma spp. can control orreduce plant disease is through induced resistanceinvolving a direct interaction with plants (De Meyer
Developing a Fully Glycosylated Full-Length SARS-CoV-2 Spike Protein Model in a Viral Membrane

This technical study describes all-atom modeling and simulation of a fully glycosylated full-length SARS-CoV-2 spike (S) protein in a viral membrane. First, starting from PDB: 6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite. Then, using the recently determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI. These fully glycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE. We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations. All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19) so that researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.
Extracellular-Regulated Protein Kinase 5-Mediated Control of p21 Expression Promotes Macrophage Proliferation Associated with Tumor Growth and Metastasis

These findings offer a new rationale for anti-ERK5 therapy to improve cancer patient outcomes by blocking the proliferative activity of tumor macrophages. The presence of immunosuppressive macrophages that become activated in the tumor microenvironment constitutes a major factor responsible for tumor growth and malignancy. In line with this knowledge, we report here that macrophage proliferation is a significant feature of advanced stages of cancer. Moreover, we have found that a high proportion of proliferating macrophages in human tumors express ERK5. ERK5 was required for supporting the proliferation of macrophages in tumor grafts in mice. Furthermore, myeloid ERK5 deficiency negatively impacted the proliferation of both resident and infiltrated macrophages in metastatic lung nodules. ERK5 maintained the capacity of macrophages to proliferate by suppressing p21 expression to halt their differentiation program. Collectively, these data provide insight into the mechanism underpinning macrophage proliferation to support malignant tumor development, thereby strengthening the value of ERK5-targeted therapies to restore antitumor immunity through the blockade of protumorigenic macrophage activation. Significance: These findings offer a new rationale for anti-ERK5 therapy to improve cancer patient outcomes by blocking the proliferative activity of tumor macrophages.
The influence of cultural attitudes to nut exposure on reported nut allergy: A pilot cross sectional study

Food allergies in children have become a common management and diagnostic concern and have a significant influence on general health-related quality of life. We investigated the prevalence of reported nut allergy between populations with different cultural attitudes to nuts during pregnancy and infancy. We conducted a survey to investigate the relationship between cultural differences in the consumption of nuts during pregnancy, breastfeeding and exposure to nuts in early childhood against the reported prevalence of nut allergy between three populations: Libyan, UK Libyan and a general UK population. The survey was administered to a representative sample of UK and Libyan parents with children aged between 3 and 16 years who were asked to report prevalence of nut allergy and to describe the factors that might affect this such as cultural behaviours and diet. A total of 1,123 parents responded. Nut allergy was defined as an allergic reaction that required medical treatment. The reported rates of nut allergy showed a significant difference in nut allergy between the Libyan populations and the general UK population with an increased odds ratio of nut allergy of ~10 when comparing the Native Libyan population to the UK population. The UK Libyan population reported the same low rate of allergic reactions as the Libyan population which were both significantly lower than the UK population (p < .0001). The Libyan populations showed significant differences from the UK population in exposure to nuts during pregnancy, breastfeeding and early infancy. The development of peanut and almond allergy through tolerance induction could be prevented by frequent and early ingestion of a moderate quantity of nuts during infancy and by maternal ingestion during pregnancy or lactation.
Gene flow in symbionts of Cladonia arbuscula

Genetic diversity in symbionts of the lichen Cladonia arbuscula was investigated. Forty-eight specimens of Cladonia arbuscula located within a 2 km range at Payuk Lake in Manitoba were collected. Population structure and method of symbiont transmission in C. arbuscula were inferred by examining the presence or absence of introns in the nuclear small subunit (SSU) ribosomal DNA (rDNA) of the mycobiont and restriction fragment length polymorphism (RFLP) of the internal transcribed spacer (ITS) rDNA in the photobiont. The mycobiont showed a high level of genetic variation and the photobiont a low level of variation within the small geographic range studied. An analysis of molecular variance of fungal genotypes showed significant population subdivision for the mycobiont when the data were analysed at P=0·05. No population subdivision was detected when P=0·001. The photobiont also showed no population subdivision. Photobiont genotypes did not correlate with mycobiont genotypes suggesting the symbionts were not transmitted together in the same propagule. Multiple fungal genotypes were also detected in C. arbuscula and possible explanations were discussed.
The Influence of Nutritional and Lifestyle Factors on Glioma Incidence

Cancers are the first main cause of premature death in developed countries. Since brain tumors, especially gliomas, are the most lethal type of cancers, risk factors for their prevalence are still being discussed. Nearly 30–50% of all cancers could be prevented by proper nutritional habits and other lifestyle factors, but their influence on the tumors of the central nervous system has not been explained completely and still requires further studies. That is why we attempted to review the available research in this field, with a special focus on the factors with the proven protective activity observed in other cancers. Adequate vegetables and antioxidants (such as vitamins C and A) provided with a diet could have a protective effect, while other factors have shown no correlation with the incidence of glioma. However, further studies are necessary to determine whether fish, coffee, and tea consumption may prevent glioma. Maintaining proper body weight and undertaking a sufficient level of daily physical activity also seem to be important. Excessive body mass index (BMI) and higher attained height have increased the risk of glioma. In order to link more accurately the chosen factors to the prevalence of gliomas, it seems necessary to conduct large cohort, prospective, controlled studies in different world regions.