Miracle-dz/UniFAR-FTUs huggingface dataset:
Uric Acid Induces Hepatic Steatosis by Generation of Mitochondrial Oxidative Stress

Background: Uric acid is an independent risk factor in fructose-induced fatty liver, but whether it is a marker or a cause remains unknown. Results: Hepatocytes exposed to uric acid developed mitochondrial dysfunction and increased de novo lipogenesis, and its blockade prevented fructose-induced lipogenesis. Conclusion: Rather than a consequence, uric acid induces fatty liver Significance: Hyperuricemic people are more prone to develop fructose-induced fatty liver. Metabolic syndrome represents a collection of abnormalities that includes fatty liver, and it currently affects one-third of the United States population and has become a major health concern worldwide. Fructose intake, primarily from added sugars in soft drinks, can induce fatty liver in animals and is epidemiologically associated with nonalcoholic fatty liver disease in humans. Fructose is considered lipogenic due to its ability to generate triglycerides as a direct consequence of the metabolism of the fructose molecule. Here, we show that fructose also stimulates triglyceride synthesis via a purine-degrading pathway that is triggered from the rapid phosphorylation of fructose by fructokinase. Generated AMP enters into the purine degradation pathway through the activation of AMP deaminase resulting in uric acid production and the generation of mitochondrial oxidants. Mitochondrial oxidative stress results in the inhibition of aconitase in the Krebs cycle, resulting in the accumulation of citrate and the stimulation of ATP citrate lyase and fatty-acid synthase leading to de novo lipogeneis. These studies provide new insights into the pathogenesis of hepatic fat accumulation under normal and diseased states.
Import of Agrobacterium T-DNA into Plant Nuclei: Two Distinct Functions of VirD2 and VirE2 Proteins

To study the mechanism of nuclear import of T-DNA, complexes consisting of the virulence proteins VirD2 and VirE2 as well as single-stranded DNA (ssDNA) were tested for import into plant nuclei in vitro. Import of these complexes was fast and efficient and could be inhibited by a competitor, a nuclear localization signal (NLS) coupled to BSA. For import of short ssDNA, VirD2 was sufficient, whereas import of long ssDNA additionally required VirE2. A VirD2 mutant lacking its C-terminal NLS was unable to mediate import of the T-DNA complexes into nuclei. Although free VirE2 molecules were imported into nuclei, once bound to ssDNA they were not imported, implying that when complexed to DNA, the NLSs of VirE2 are not exposed and thus do not function. RecA, another ssDNA binding protein, could substitute for VirE2 in the nuclear import of T-DNA but not in earlier events of T-DNA transfer to plant cells. We propose that VirD2 directs the T-DNA complex to the nuclear pore, whereas both proteins mediate its passage through the pore. Therefore, by binding to ssDNA, VirE2 may shape the T-DNA complex such that it is accepted for translocation into the nucleus.
Information seeking and mediated searching. Part 5. User-intermediary interaction

This article is the fifth in a series of articles from our study examining information-seeking behavior in relation to information-retrieval (IR) interaction. This article focuses on the examination of the interaction variables within Saracevic's (1989) triadic IR model. The analysis involved an examination of the information-searching behavior of academic researchers during a mediated interaction with an IR system, particularly concentrating on the interaction between the information seeker, the search intermediary, and the IR system. To explore the variables during mediated search interaction, two small-scale studies of mediated on-line searching were conducted at the University of Sheffield. The studies involved mainly qualitative data analysis of interview transcripts and on-line search results, together with quantitative data analysis of questionnaire results. The studies specifically investigated: (1) aspects of the mediated search process, (2) relevant information sources, and (3) interaction measures derived from search logs and tape transcripts, and related interaction measures. Findings include: (1) a number of different types of interactions were identified, (2) the presearching interactions between information seeker and intermediary aided the information seeker to identify their idea and problem, and (3) most information seekers in this study were at the problem definition stage or problem resolution stage following the search process. From this research, it is clear that the interaction did affect the search process. The intermediary helped the users to identify their search terms more clearly and focus on the references obtained. In most cases, the users and intermediary considered the communication process very effective, and the interactions that took place during the on-line search were found to affect the users' perceptions of the problem, personal knowledge, and relevance judgments. The interaction process aided the users to obtain very useful results with help from the intermediary. In general, the users gave a positive evaluation of the retrieved answers in terms of focus, completeness, novelty, and degree of nonrelevancy.
A pilot study of an emotional intelligence training intervention for a paediatric team

Objective Emotional intelligence (EI) is the individual's ability to perceive, understand and manage emotion and to understand and relate effectively to others. We examined the degree to which EI training may be associated with a change in EI among different medical personnel and patient satisfaction. Design, setting and participants The EI of 17 physicians and 10 nurses in paediatric ward was prospectively evaluated with Bar-On's EI at baseline and after 18 months. 11 physicians who did not undergo the intervention served as controls. Interventions The intervention consisted of a training programme comprising group discussions, simulations and case studies. Main outcomes and measures Pre-emotional quotient inventory (EQ-i) and post-EQ-i scores and patient satisfaction surveys of nurse and physicians pre-intervention and post-intervention were analysed. Results The mean overall EI score of the study sample rose from 99.0±9.6 (both plus and minus mathematical operations standing for SD) at baseline to 105.4±10 (p<0.000) after 18 months, with the most robust increase (nearly 6%; p<0.003) manifested among physicians. In contrast, the control group's EI scores did not change over this period. Within the intervention group, physicians displayed a statistically significant increase in three of the five EI dimensions, compared with only one of the five EI dimensions for nurses. Patient satisfaction scores relating to physician care rose from 4.4 pre-intervention to 4.7 post-intervention (p=0.03). Conclusion An EI intervention led to an overall increase in EI scores, with a significant improvement in patient satisfaction. These findings suggest important potential benefits for both staff and their patients.
Muscle abnormalities in Drosophila melanogaster heldup mutants are caused by missing or aberrant troponin-I isoforms

We have investigated the molecular bases of muscle abnormalities in four Drosophila melanogaster heldup mutants. We find that the heldup gene encodes troponin-I, one of the principal regulatory proteins associated with skeletal muscle thin filaments. heldup3, heldup4, and heldup5 mutants, all of which have grossly abnormal flight muscle myofibrils, lack mRNAs encoding one or more troponin-I isoforms. In contrast, heldup2, an especially interesting mutant wherein flight muscles are atrophic, synthesizes the complete mRNA complement. By sequencing mutant troponin-I cDNAs we demonstrate that the molecular basis for muscle degeneration in heldup2 is conversion of an invariant alanine residue to valine. We finally show that degeneration of heldup2 thin filament/Z-disc networks can be prevented by eliminating thick filaments from flight muscles using a null allele of the sarcomeric myosin heavy chain gene. This latter observation suggests that actomyosin interactions exacerbate the structural or functional defect resulting from the troponin-I mutation.
Wound Healing Assessment: Does the Ideal Methodology for a Research Setting Exist?

Introduction:Studies on dressings frequently measure wound healing to demonstrate performance. Knowledge of existing methodologies available for wound healing assessment, including their advantages and limitations, is paramount when evaluating the literature on dressings. Methodology:Medline and Cochrane databases were searched for wound healing assessment methodologies used in research or in clinical practice. Results:Twenty-nine methodologies were identified and classified into 8 categories: scales (n = 4), one-dimensional measurements (n = 2), area measurements (n = 4), volume measurements (n = 6), 3-dimensional wound reproduction systems (n = 5), methodologies based on wound physical characteristics (n = 3), rates and surrogates end point calculated from variation in wound dimensions (n = 4), and time to wound healing (n = 1). The main problems encountered during wound healing assessment include the following: boundary definition, assessor's contact with the wound, irregular wound shape, and difficulty in evaluating early healing. Conclusion:At this time, an ideal methodology does not exist. Research in this area is lacking and should be the focus in wound healing evaluation.
Polycystic ovary syndrome and its impact on women’s quality of life: More than just an endocrine disorder

In the past, polycystic ovary syndrome has been looked at primarily as an endocrine disorder. Studies now show that polycystic ovary syndrome is a metabolic, hormonal, and psychosocial disorder that impacts a patient’s quality of life. It is extremely important to holistically treat these patients early on to help them deal with the emotional stress that is often overlooked with polycystic ovary syndrome. Early diagnosis and long term management can help control polycystic ovary syndrome so that women can still live a healthy active life and avoid long-term complications such as metabolic syndrome and cardiovascular diseases.
Failure Behavior of Plain Weave Fabric Laminates under On-Axis Uniaxial Tensile Loading: I—Laminate Geometry

Mathematical expressions are presented for defining the geometry of the two-dimensional orthogonal plain weave fabric laminates. The geometry was defined with the view of developing the analytical models for the prediction of the thermo-mechanical behavior. The actual strand cross-sectional geometry. possible gap between adjacent strands, strand undulation and continuity along both the warp and fill directions are considered in the mathematical expressions. Simulated geometry was compared with the actual photomicrographs of the laminate cross sections. A good match was observed.
From Actions to Habits

Recent work on the role of overlapping cerebral networks in action selection and habit formation has important implications for alcohol addiction research. As reviewed below, (1) these networks, which all involve a group of deep-brain structures called the basal ganglia, are associated with distinct behavioral control processes, such as reward-guided Pavlovian conditional responses, goal-directed instrumental actions, and stimulus-driven habits; (2) different stages of action learning are associated with different networks, which have the ability to change (i.e., plasticity); and (3) exposure to alcohol and other addictive drugs can have profound effects on these networks by influencing the mechanisms underlying neural plasticity.
Electromagnetic scattering measurements on a fractal surface

In this paper we present a procedure devoted to validate innovative theories on the electromagnetic scattering from natural surfaces, using fractal functions for the surface description. A fractal surface has been built as a superposition of cardboard and aluminium layers, according with a computer design based on the Weierstrass-Mandelbrot (WM) fractal function. Its statistical properties have been verified with optical measurements. The electromagnetic field scattered at X band from the built surface has been measured in controlled environment as a function of the incidence angle. Obtained results have been compared with those of the Kirchhoff Approximation (KA) and the Small Perturbation Method (SPM) in conjunction with the fractional Brownian motion (fBm). Congruence and discrepancies of measured data with theoretical results are discussed, providing a validation of the methods
Nab 3 Facilitates the Function of the TRAMP Complex in RNA Processing via Recruitment of Rrp 6 Independent of Nrd 1

Non-coding RNAs (ncRNAs) play critical roles in gene regulation. In eukaryotic cells, ncRNAs are processed and/or degraded by the nuclear exosome, a ribonuclease complex containing catalytic subunits Dis3 and Rrp6. The TRAMP (Trf4/5-Air1/2-Mtr4 polyadenylation) complex is a critical exosome cofactor in budding yeast that stimulates the exosome to process/degrade ncRNAs and human TRAMP components have recently been identified. Importantly, mutations in exosome and exosome cofactor genes cause neurodegenerative disease. How the TRAMP complex interacts with other exosome cofactors to orchestrate regulation of the exosome is an open question. To identify novel interactions of the TRAMP exosome cofactor, we performed a high copy suppressor screen of a thermosensitive air1/2 TRAMP mutant. Here, we report that the Nab3 RNA-binding protein of the Nrd1-Nab3-Sen1 (NNS) complex is a potent suppressor of TRAMP mutants. Unlike Nab3, Nrd1 and Sen1 do not suppress TRAMP mutants and Nrd1 binding is not required for Nab3-mediated suppression of TRAMP suggesting an independent role for Nab3. Critically, Nab3 decreases ncRNA levels in TRAMP mutants, Nab3-mediated suppression of air1/2 cells requires the nuclear exosome component, Rrp6, and Nab3 directly binds Rrp6. We extend this analysis to identify a human RNA binding protein, RALY, which shares identity with Nab3 and can suppress TRAMP mutants. These results suggest that Nab3 facilitates TRAMP function by recruiting Rrp6 to ncRNAs for processing/degradation independent of Nrd1. The data raise the intriguing possibility that Nab3 and Nrd1 can function independently to recruit Rrp6 to ncRNA targets, providing combinatorial flexibility in RNA processing.
Horizontal Transfer of Entire Genomes via Mitochondrial Fusion in the Angiosperm Amborella

Shaping Plant Evolution Amborella trichopoda is understood to be the most basal extant flowering plant and its genome is anticipated to provide insights into the evolution of plant life on Earth (see the Perspective by Adams). To validate and assemble the sequence, Chamala et al. (p. 1516) combined fluorescent in situ hybridization (FISH), genomic mapping, and next-generation sequencing. The Amborella Genome Project (p. 10.1126/science.1241089) was able to infer that a whole-genome duplication event preceded the evolution of this ancestral angiosperm, and Rice et al. (p. 1468) found that numerous genes in the mitochondrion were acquired by horizontal gene transfer from other plants, including almost four entire mitochondrial genomes from mosses and algae. Much of the mitochondrial DNA genome of the flowering plant Amborella trichopoda originated from other organisms. We report the complete mitochondrial genome sequence of the flowering plant Amborella trichopoda. This enormous, 3.9-megabase genome contains six genome equivalents of foreign mitochondrial DNA, acquired from green algae, mosses, and other angiosperms. Many of these horizontal transfers were large, including acquisition of entire mitochondrial genomes from three green algae and one moss. We propose a fusion-compatibility model to explain these findings, with Amborella capturing whole mitochondria from diverse eukaryotes, followed by mitochondrial fusion (limited mechanistically to green plant mitochondria) and then genome recombination. Amborella’s epiphyte load, propensity to produce suckers from wounds, and low rate of mitochondrial DNA loss probably all contribute to the high level of foreign DNA in its mitochondrial genome.
Stem Cells, Progenitor Cells, and Lineage Decisions in the Ovary

Exploring stem cells in the mammalian ovary has unleashed a Pandora's box of new insights and questions. Recent evidence supports the existence of stem cells of a number of the different cell types within the ovary. The evidence for a stem cell model producing mural granulosa cells and cumulus cells is strong, despite a limited number of reports. The recent identification of a precursor granulosa cell, the gonadal ridge epithelial-like cell, is exciting and novel. The identification of female germline (oogonial) stem cells is still very new and is currently limited to just a few species. Their origins and physiological roles, if any, are unknown, and their potential to produce oocytes and contribute to follicle formation in vivo lacks robust evidence. The precursor of thecal cells remains elusive, and more compelling data are needed. Similarly, claims of very small embryonic-like cells are also preliminary. Surface epithelial cells originating from gonadal ridge epithelial-like cells and from the mesonephric epithelium at the hilum of the ovary have also been proposed. Another important issue is the role of the stroma in guiding the formation of the ovary, ovigerous cords, follicles, and surface epithelium. Immune cells may also play key roles in developmental patterning, given their critical roles in corpora lutea formation and regression. Thus, while the cellular biology of the ovary is extremely important for its major endocrine and fertility roles, there is much still to be discovered. This review draws together the current evidence and perspectives on this topic.
Endotoxin neutralization by an O-antigen specific monoclonal antibody: A potential novel therapeutic approach against Klebsiella pneumoniae ST258

ABSTRACT Klebsiella pneumoniae ST258 is a globally distributed multi-drug resistant pathogen responsible for severe invasive infections. In this study, the different virulence potential of K. pneumoniae ST258 isolates in endotoxin susceptible versus resistant animal models was shown. Furthermore, ST258 clinical isolates were found highly sensitive to the bactericidal effect of naive animal and human serum. These observations imply that LPS, released from the rapidly lysed bacteria, may contribute to the high mortality associated with ST258 bacteremia cases. A humanized version (mAb A1102) of a previously described murine mAb specific for the conserved LPS O-antigen, was tested for endotoxin neutralization. A1102 was able to neutralize TLR-4 activation by ST258-derived LPS in vitro with an efficacy exceeding that of polymyxin B by 3 orders of magnitude. Passive immunization with A1102 afforded a significant level of protection in a galactosamine-sensitized mouse model of endotoxemia, induced by ST258-derived LPS, or upon challenge with live bacteria. Efficacy was retained using an aglycosylated IgG, as well as upon complement depletion, suggesting that Fc-independent endotoxin neutralization may be the main protective mechanism in this model, in spite of the complement-dependent bactericidal and opsonic activities additionally observed for A1102 in vitro. Furthermore, rabbits that are naturally highly susceptible to endotoxin, were also significantly protected by low doses of A1102 when challenged with an ST258 strain. Given this unique mode of action and the high protective efficacy of this mAb, passive immunization, as prophylactic or adjunct therapeutic approach for the treatment of infections caused by ST258 isolates should be considered.
Genetically Determined Heterogeneity in Hemoglobin Scavenging and Susceptibility to Diabetic Cardiovascular Disease

Abstract —A major function of haptoglobin (Hp) is to bind hemoglobin (Hb) to form a stable Hp‐Hb complex and thereby prevent Hb‐induced oxidative tissue damage. Clearance of the Hp‐Hb complex can be mediated by the monocyte/macrophage scavenger receptor CD163. We recently demonstrated that diabetic individuals homozygous for the Hp 2 allele (Hp 2–2) were at 500% greater risk of cardiovascular disease (CVD) compared with diabetic individuals homozygous for the Hp 1 allele (Hp 1–1). No differences in risk by Hp type were seen in individuals without diabetes. To understand the relationship between the Hp polymorphism and diabetic CVD, we sought to identify differences in antioxidant and scavenging functions between the Hp types and to determine how these functions were modified in diabetes. The scavenging function of Hp was assessed using rhodamine‐tagged and 125I‐Hp in cell lines stably transfected with CD163 and in macrophages expressing endogenous CD163. We found that the rate of clearance of Hp 1–1‐Hb by CD163 is markedly greater than that of Hp 2–2‐Hb. Diabetes is associated with an increase in the nonenzymatic glycosylation of serum proteins, including Hb. The antioxidant function of Hp was assessed with glycosylated and nonglycosylated Hb. We identified a severe impairment in the ability of Hp to prevent oxidation mediated by glycosylated Hb. We propose that the specific interaction between diabetes, CVD, and Hp genotype is the result of the heightened urgency of rapidly clearing glycosylated Hb‐Hp complexes from the subendothelial space before they can oxidatively modify low‐density lipoprotein to atherogenic oxidized low‐density lipoprotein. (Circ Res. 2003;92:1193–1200.)
Development of hollow fiber-supported liquid-phase microextraction and HPLC-DAD method for the determination of pyrethroid metabolites in human and rat urine.

A simple hollow fiber liquid-phase microextraction method for the determination of synthetic pyrethroid metabolites, 3-phenoxybenzoic acid and 4-hydroxy-3-phenoxybenzoic acid, in human and rat urine was developed and validated. A polypropylene hollow fiber tightly fitted onto a Nylon rod and impregnated with organic solvent served as a disposable extraction device. Desorption of analytes was carried out in NaOH solution, analyzed further by gradient HPLC and diode array detection method. Important factors were identified using Taguchi OA16 (4(5) ) orthogonal array design and further optimized using univariate approach. The optimum method performance was observed when 1 mL of urine hydrolyzed with 0.2 mL of concentrated HCl was further supplemented with 100 mg of NaCl and extracted for 120 min into dihexyl ether immobilized in the pores of the hollow fiber. Metabolites were desorbed into 0.1 mL of 0.1 M NaOH for another 120 min. Limits of detection and quantitation of 15 and 50 ng/mL were obtained for both analytes. Relative standard deviations of 1.6-12.6% over the linear range (50-10,000 ng/mL, r > 0.9906) were observed. Intra- and inter-day accuracies of the method ranged from 98.3 to 109.5% and from 93.3 to 110.9%, respectively. The optimized method was applied to the analysis of real urine samples collected from rats exposed orally to cypermethrin.
NEUROPATHOLOGICAL STUDY OF A CASE OF AUTISTIC SYNDROME WITH SEVERE MENTAL RETARDATION

Infantile autism is a syndrome of unknown aetiology and unknown neuro‐anatomic substrate. The authors report a histological study of the brain of a well‐documented 16‐year‐old female with autistic syndrome and severe mental retardation, using direct microscopic examination of the whole brain. The major findings are low brain weight, a thin corpus callosum and ventricular dilatation. No abnormalities were found in the hippocampus or cerebellum. Excessive axonal elimination during brain development is hypothesized. The relations of hypothetical developmental events with the clinical features of autistic syndrome are discussed.