Miracle-dz/UniFAR-FTUs huggingface dataset:
Nanoparticle-Induced Complement Activation: Implications for Cancer Nanomedicine

Nanoparticle-based anticancer medications were first approved for cancer treatment almost 2 decades ago. Patients benefit from these approaches because of the targeted-drug delivery and reduced toxicity, however, like other therapies, adverse reactions often limit their use. These reactions are linked to the interactions of nanoparticles with the immune system, including the activation of complement. This activation can cause well-characterized acute inflammatory reactions mediated by complement effectors. However, the long-term implications of chronic complement activation on the efficacy of drugs carried by nanoparticles remain obscured. The recent discovery of protumor roles of complement raises the possibility that nanoparticle-induced complement activation may actually reduce antitumor efficacy of drugs carried by nanoparticles. We discuss here the initial evidence supporting this notion. Better understanding of the complex interactions between nanoparticles, complement, and the tumor microenvironment appears to be critical for development of nanoparticle-based anticancer therapies that are safer and more efficacious.
Physiological, Nutritional and Metabolomic Responses of Tomato Plants After the Foliar Application of Amino Acids Aspartic Acid, Glutamic Acid and Alanine

Agriculture is facing a great number of different pressures due to the increase in population and the greater amount of food it demands, the environmental impact due to the excessive use of conventional fertilizers, and climate change, which subjects the crops to extreme environmental conditions. One of the solutions to these problems could be the use of biostimulant products that are rich in amino acids (AAs), which substitute and/or complement conventional fertilizers and help plants adapt to climate change. To formulate these products, it is first necessary to understand the role of the application of AAs (individually or as a mixture) in the physiological and metabolic processes of crops. For this, research was conducted to assess the effects of the application of different amino acids (Aspartic acid (Asp), Glutamic acid (Glu), L-Alanine (Ala) and their mixtures Asp + Glu and Asp + Glu + Ala on tomato seedlings (Solanum lycopersicum L.). To understand the effect of these treatments, morphological, physiological, ionomic and metabolomic studies were performed. The results showed that the application of Asp + Glu increased the growth of the plants, while those plants that received Ala had a decreased dry biomass of the shoots. The greatest increase in the growth of the plants with Asp + Glu was related with the increase in the net CO2 assimilation, the increase of proline, isoleucine and glucose with respect to the rest of the treatments. These data allow us to conclude that there is a synergistic effect between Aspartic acid and Glutamic acid, and the amino acid Alanine produces phytotoxicity when applied at 15 mM. The application of this amino acid altered the synthesis of proline and the pentose-phosphate route, and increased GABA and trigonelline.
Dance on the Brain: Enhancing Intra- and Inter-Brain Synchrony

Dance has traditionally been viewed from a Eurocentric perspective as a mode of self-expression that involves the human body moving through space, performed for the purposes of art, and viewed by an audience. In this Hypothesis and Theory article, we synthesize findings from anthropology, sociology, psychology, dance pedagogy, and neuroscience to propose The Synchronicity Hypothesis of Dance, which states that humans dance to enhance both intra- and inter-brain synchrony. We outline a neurocentric definition of dance, which suggests that dance involves neurobehavioral processes in seven distinct areas including sensory, motor, cognitive, social, emotional, rhythmic, and creative. We explore The Synchronicity Hypothesis of Dance through several avenues. First, we examine evolutionary theories of dance, which suggest that dance drives interpersonal coordination. Second, we examine fundamental movement patterns, which emerge throughout development and are omnipresent across cultures of the world. Third, we examine how each of the seven neurobehaviors increases intra- and inter-brain synchrony. Fourth, we examine the neuroimaging literature on dance to identify the brain regions most involved in and affected by dance. The findings presented here support our hypothesis that we engage in dance for the purpose of intrinsic reward, which as a result of dance-induced increases in neural synchrony, leads to enhanced interpersonal coordination. This hypothesis suggests that dance may be helpful to repattern oscillatory activity, leading to clinical improvements in autism spectrum disorder and other disorders with oscillatory activity impairments. Finally, we offer suggestions for future directions and discuss the idea that our consciousness can be redefined not just as an individual process but as a shared experience that we can positively influence by dancing together.
Prevalence and Predictors of Antimicrobial Resistance Among Enterococcus spp. From Dogs Presented at a Veterinary Teaching Hospital, South Africa

Background: While surveillance of antimicrobial drug resistance is ongoing in human medicine in South Africa, there is no such activity being performed in veterinary medicine. As a result, there is a need to investigate antimicrobial resistance among enterococci isolated from dogs in South Africa to improve understanding of the status of antimicrobial drug resistance given its public and veterinary public health importance. This study investigated antimicrobial resistance and factors associated with resistance profiles of enterococci isolated from dogs presented for veterinary care at a veterinary teaching hospital in South Africa. Methods: In total 102 Enterococcus isolated between 2007 and 2011 by a bacteriology laboratory at a teaching hospital were included in this study. Antimicrobial susceptibility of the isolates was determined against a panel of 18 antimicrobials using the Kirby Bauer disc diffusion technique. Univariate analysis was used to assess simple associations between year, season, breed group, age group, sex, and specimen as covariates and extensive drug resistance (XDR) as the outcome. Variables that were significant in the univariate analysis at a generous p-value ≤ 0.2 were included in the multivariable logistic models to investigate predictors of XDR. Results: All the Enterococcus isolates were resistant to at least one antimicrobial. High proportions of isolates were resistant against lincomycin (93%), kanamycin (87%), orbifloxacin (85%), and aminogycoside-lincosamide (77%). Ninety three percent (93%), 35.3, and 8.8% of the isolates exhibited multi-drug, extensive-drug and pan-drug resistance, respectively. Only year was significantly (p = 0.019) associated with extensive-drug resistance. Conclusion: Given the zoonotic potential of Enterococcus spp. , the high antimicrobial resistance and multi-drug resistance observed in this study are a public health concern from one health perspective. The identified resistance to various antimicrobials may be useful in guiding clinicians especially in resource scarce settings where it is not always possible to perform AST when making treatment decisions.
Electrical Conductivity and Thermodynamic Equilibrium in Nickel Oxide

The electrical conductivity of nickel oxide has been studied at temperatures between 600° and 1350°C and partial pressures of oxygen between 1 atm and 10−4 atm. The slope of log conductivity vs reciprocal temperature plots increases when the temperature is high enough for the sample to come into thermodynamic equilibrium with the atmosphere, and the temperature at which the change in slope occurs is observed to depend on the rate of heating or cooling of the crystal. The heat of formation of nickel vacancies may be determined from the magnitude of the change in slope by a simple calculation. Nickel oxide is a p‐type semiconductor [M. Verwey, M. Haaijman, H. Romeijn, and M. van Oosterhout, Philips Research Repts. 5, 173 (1950)] in which the conductivity is proportional to the concentration of Ni3+ ions in the lattice. When thermodynamic equilibrium is established with the atmosphere the conductivity is proportional to the ⅙th power of the oxygen partial pressure.The analysis of the conduction mechanism and.
In vivo Cross-Linking MS of the Complement System MAC Assembled on Live Gram-Positive Bacteria

Protein–protein interactions are central in many biological processes, but they are challenging to characterize, especially in complex samples. Protein cross-linking combined with mass spectrometry (MS) and computational modeling is gaining increased recognition as a viable tool in protein interaction studies. Here, we provide insights into the structure of the multicomponent human complement system membrane attack complex (MAC) using in vivo cross-linking MS combined with computational macromolecular modeling. We developed an affinity procedure followed by chemical cross-linking on human blood plasma using live Streptococcus pyogenes to enrich for native MAC associated with the bacterial surface. In this highly complex sample, we identified over 100 cross-linked lysine–lysine pairs between different MAC components that enabled us to present a quaternary model of the assembled MAC in its native environment. Demonstrating the validity of our approach, this MAC model is supported by existing X-ray crystallographic and electron cryo-microscopic models. This approach allows the study of protein–protein interactions in native environment mimicking their natural milieu. Its high potential in assisting and refining data interpretation in electron cryo-tomographic experiments will be discussed.
Estimation of Heterogeneous Restricted Mean Survival Time Using Random Forest

Estimation and prediction of heterogeneous restricted mean survival time (hRMST) is of great clinical importance, which can provide an easily interpretable and clinically meaningful summary of the survival function in the presence of censoring and individual covariates. The existing methods for the modeling of hRMST rely on proportional hazards or other parametric assumptions on the survival distribution. In this paper, we propose a random forest based estimation of hRMST for right-censored survival data with covariates and prove a central limit theorem for the resulting estimator. In addition, we present a computationally efficient construction for the confidence interval of hRMST. Our simulations show that the resulting confidence intervals have the correct coverage probability of the hRMST, and the random forest based estimate of hRMST has smaller prediction errors than the parametric models when the models are mis-specified. We apply the method to the ovarian cancer data set from The Cancer Genome Atlas (TCGA) project to predict hRMST and show an improved prediction performance over the existing methods. A software implementation, srf using R and C++, is available at https://github.com/lmy1019/SRF.
Overloaded Adeno-Associated Virus as a Novel Gene Therapeutic Tool for Otoferlin-Related Deafness

Hearing impairment is the most common sensory disorder in humans. So far, rehabilitation of profoundly deaf subjects relies on direct stimulation of the auditory nerve through cochlear implants. However, in some forms of genetic hearing impairment, the organ of Corti is structurally intact and therapeutic replacement of the mutated gene could potentially restore near natural hearing. In the case of defects of the otoferlin gene (OTOF), such gene therapy is hindered by the size of the coding sequence (~6 kb) exceeding the cargo capacity (<5 kb) of the preferred viral vector, adeno-associated virus (AAV). Recently, a dual-AAV approach was used to partially restore hearing in deaf otoferlin knock-out (Otof-KO) mice. Here, we employed in vitro and in vivo approaches to assess the gene-therapeutic potential of naturally-occurring and newly-developed synthetic AAVs overloaded with the full-length Otof coding sequence. Upon early postnatal injection into the cochlea of Otof-KO mice, overloaded AAVs drove specific expression of otoferlin in ~30% of all IHCs, as demonstrated by immunofluorescence labeling and polymerase chain reaction. Recordings of auditory brainstem responses and a behavioral assay demonstrated partial restoration of hearing. Together, our results suggest that viral gene therapy of DFNB9—using a single overloaded AAV vector—is indeed feasible, reducing the complexity of gene transfer compared to dual-AAV approaches.
Premature Birth and Developmental Programming: Mechanisms of Resilience and Vulnerability

The third trimester of pregnancy represents a sensitive phase for infant brain plasticity when a series of fast-developing cellular events (synaptogenesis, neuronal migration, and myelination) regulates the development of neural circuits. Throughout this dynamic period of growth and development, the human brain is susceptible to stress. Preterm infants are born with an immature brain and are, while admitted to the neonatal intensive care unit, precociously exposed to stressful procedures. Postnatal stress may contribute to altered programming of the brain, including key systems such as the hypothalamic–pituitary–adrenal axis and the autonomic nervous system. These neurobiological systems are promising markers for the etiology of several affective and social psychopathologies. As preterm birth interferes with early development of stress-regulatory systems, early interventions might strengthen resilience factors and might help reduce the detrimental effects of chronic stress exposure. Here we will review the impact of stress following premature birth on the programming of neurobiological systems and discuss possible stress-related neural circuits and pathways involved in resilience and vulnerability. Finally, we discuss opportunities for early intervention and future studies.
Bacterial 3′UTRs: A Useful Resource in Post-transcriptional Regulation

Bacterial messenger RNAs (mRNAs) are composed of 5′ and 3′ untranslated regions (UTRs) that flank the coding sequences (CDSs). In eukaryotes, 3′UTRs play key roles in post-transcriptional regulatory mechanisms. Shortening or deregulation of these regions is associated with diseases such as cancer and metabolic disorders. Comparatively, little is known about the functions of 3′UTRs in bacteria. Over the past few years, 3′UTRs have emerged as important players in the regulation of relevant bacterial processes such as virulence, iron metabolism, and biofilm formation. This MiniReview is an update for the different 3′UTR-mediated mechanisms that regulate gene expression in bacteria. Some of these include 3′UTRs that interact with the 5′UTR of the same transcript to modulate translation, 3′UTRs that are targeted by specific ribonucleases, RNA-binding proteins and small RNAs (sRNAs), and 3′UTRs that act as reservoirs of trans-acting sRNAs, among others. In addition, recent findings regarding a differential evolution of bacterial 3′UTRs and its impact in the species-specific expression of orthologous genes are also discussed.
Defect formation in CdTe during laser‐induced doping and application to the manufacturing nuclear radiation detectors

The peculiarities of electrical properties of In/CdTe/Au diodes, fabricated by the laser-induced doping procedure, have been studied. The measurements of time dependences of reverse biased current of a great number of different samples revealed three types of the leakage current density variations with time. These variations were attributed to proper CdTe defects as well as point and extended defects generated in the act of laser-induced doping of CdTe wafers and following fabrication of pixel detectors. The optimal conditions of laser-induced In-doping of CdTe wafers and formation of electrodes were elaborated. The fabricated detectors had sharp I-V characteristics with a low leakage current, possessed a high energy resolution at room temperature and showed promise for nuclear radiation imaging devices.
Dynamic Viscoelastic Modulus of Associative Polymer Networks: Off-Lattice Simulations, Theory and Comparison to Experiments

An off-lattice simulation model for associative polymer gels as introduced recently (Groot, R. D. ; Agterof, W. G. M. J. Chem. Phys. 1994, 100, 1649) has been applied to obtain the mechanical spectrum as a function of frequency and polymer concentration, using a Green-Kubo relation for the time-dependent modulus. Two stages of relaxation are observable in our simulations. The early-time decay is consistent with a -2/3 power law, whose form is insensitive to large variations in polymer concentration, association lifetime, and degree of association. The late stage, which relaxes like the end-to-end vector in the Rouse model, has a characteristic stress that scales as the cube of the concentration and a relaxation time that is proportional to the monomer-monomer dissociation rate. The simulation results have been compared with experiments found in the literature for several physical gels. The quantitative agreement calls into question other postulated mechanisms involving hydrodynamic interaction or reptation, since the simulation contains neither of these features. As an alternative explanation for the observed early-time decay, an explicit relation between the power law exponent and the polymer fractal dimension is given.
Alcohol Induced Brain and Liver Damage: Advantages of a Porcine Alcohol Use Disorder Model

Alcohol is one of the most commonly abused intoxicants with 1 in 6 adults at risk for alcohol use disorder (AUD) in the United States. As such, animal models have been extensively investigated with rodent AUD models being the most widely studied. However, inherent anatomical and physiological differences between rodents and humans pose a number of limitations in studying the complex nature of human AUD. For example, rodents differ from humans in that rodents metabolize alcohol rapidly and do not innately demonstrate voluntary alcohol consumption. Comparatively, pigs exhibit similar patterns observed in human AUD including voluntary alcohol consumption and intoxication behaviors, which are instrumental in establishing a more representative AUD model that could in turn delineate the risk factors involved in the development of this disorder. Pigs and humans also share anatomical similarities in the two major target organs of alcohol- the brain and liver. Pigs possess gyrencephalic brains with comparable cerebral white matter volumes to humans, thus enabling more representative evaluations of susceptibility and neural tissue damage in response to AUD. Furthermore, similarities in the liver result in a comparable rate of alcohol elimination as humans, thus enabling a more accurate extrapolation of dosage and intoxication level to humans. A porcine model of AUD possesses great translational potential that can significantly advance our current understanding of the complex development and continuance of AUD in humans.
A Systematic Review of Plants With Antibacterial Activities: A Taxonomic and Phylogenetic Perspective

Background: Antimicrobial resistance represents a serious threat to human health across the globe. The cost of bringing a new antibiotic from discovery to market is high and return on investment is low. Furthermore, the development of new antibiotics has slowed dramatically since the 1950s’ golden age of discovery. Plants produce a variety of bioactive secondary metabolites that could be used to fuel the future discovery pipeline. While many studies have focused on specific aspects of plants and plant natural products with antibacterial properties, a comprehensive review of the antibacterial potential of plants has never before been attempted. Objectives: This systematic review aims to evaluate reports on plants with significant antibacterial activities. Methods: Following the PRISMA model, we searched three electronic databases: Web of Science, PubMed and SciFinder by using specific keywords: “plant,” “antibacterial,” “inhibitory concentration. ” Results: We identified a total of 6,083 articles published between 1946 and 2019 and then reviewed 66% of these (4,024) focusing on articles published between 2012 and 2019. A rigorous selection process was implemented using clear inclusion and exclusion criteria, yielding data on 958 plant species derived from 483 scientific articles. Antibacterial activity is found in 51 of 79 vascular plant orders throughout the phylogenetic tree. Most are reported within eudicots, with the bulk of species being asterids. Antibacterial activity is not prominent in monocotyledons. Phylogenetic distribution strongly supports the concept of chemical evolution across plant clades, especially in more derived eudicot families. The Lamiaceae, Fabaceae and Asteraceae were the most represented plant families, while Cinnamomum verum, Rosmarinus vulgaris and Thymus vulgaris were the most studied species. South Africa was the most represented site of plant collection. Crude extraction in methanol was the most represented type of extraction and leaves were the main plant tissue investigated. Finally, Staphylococcus aureus was the most targeted pathogenic bacteria in these studies. We closely examine 70 prominent medicinal plant species from the 15 families most studied in the literature. Conclusion: This review depicts the current state of knowledge regarding antibacterials from plants and provides powerful recommendations for future research directions.
The Role of Notch and Wnt Signaling in MSC Communication in Normal and Leukemic Bone Marrow Niche

Notch and Wnt signaling are highly conserved intercellular communication pathways involved in developmental processes, such as hematopoiesis. Even though data from literature support a role for these two pathways in both physiological hematopoiesis and leukemia, there are still many controversies concerning the nature of their contribution. Early studies, strengthened by findings from T-cell acute lymphoblastic leukemia (T-ALL), have focused their investigation on the mutations in genes encoding for components of the pathways, with limited results except for B-cell chronic lymphocytic leukemia (CLL); in because in other leukemia the two pathways could be hyper-expressed without genetic abnormalities. As normal and malignant hematopoiesis require close and complex interactions between hematopoietic cells and specialized bone marrow (BM) niche cells, recent studies have focused on the role of Notch and Wnt signaling in the context of normal crosstalk between hematopoietic/leukemia cells and stromal components. Amongst the latter, mesenchymal stromal/stem cells (MSCs) play a pivotal role as multipotent non-hematopoietic cells capable of giving rise to most of the BM niche stromal cells, including fibroblasts, adipocytes, and osteocytes. Indeed, MSCs express and secrete a broad pattern of bioactive molecules, including Notch and Wnt molecules, that support all the phases of the hematopoiesis, including self-renewal, proliferation and differentiation. Herein, we provide an overview on recent advances on the contribution of MSC-derived Notch and Wnt signaling to hematopoiesis and leukemia development.