Miracle-dz/UniFAR-FTUs huggingface dataset:
Stable isotope aided nuclear magnetic resonance study to investigate the receptor-binding site of human interleukin 1 beta.

Resonance assignments for interleukin 1 beta at neutral pH were made by using three-dimensional NMR in combination with specific labeling and double-labeling methods with stable isotopes. On the basis of the present assignments, 15N single-quantum coherence spectra of N-terminal truncated and fusion mutants were compared with that of the wild-type. Although these mutants have reduced biological activity, they showed 15N-SQC spectra similar to that of the wild-type. However, small but significant chemical shift changes were observed for amino acid residues within a loop 86-99, in spite of the modification at the N-terminus, supporting the idea that this loop forms a biologically active part of interleukin 1 beta. Receptor-binding activity was studied for mutants (Asp-93)-, (Leu-93)- and des-(Arg-98)interleukin 1 beta's. The results show significant loss of the receptor-binding activity. The N-terminus, the C-terminus, and the loop 86-99 form a part of the open end of a beta-barrel [Finzel, B. C. , Clancy, L. L. , Holland, D. R. , Muchmore, S. W. , Watenpaugh, K. D. , & Einspahr, H. M. (1989) J. Mol. Biol. 209, 779-791; Clore, G. M. , Wingfield, P. T. , & Gronenborn, A. M. (1991) Biochemistry 30, 2315-2323], which forms the receptor-binding site of IL-1 beta.
Effect of Rhodopsin Phosphorylation on Dark Adaptation in Mouse Rods

Rhodopsin is a prototypical G-protein-coupled receptor (GPCR) that is activated when its 11-cis-retinal moiety is photoisomerized to all-trans retinal. This step initiates a cascade of reactions by which rods signal changes in light intensity. Like other GPCRs, rhodopsin is deactivated through receptor phosphorylation and arrestin binding. Full recovery of receptor sensitivity is then achieved when rhodopsin is regenerated through a series of steps that return the receptor to its ground state. Here, we show that dephosphorylation of the opsin moiety of rhodopsin is an extremely slow but requisite step in the restoration of the visual pigment to its ground state. We make use of a novel observation: isolated mouse retinae kept in standard media for routine physiologic recordings display blunted dephosphorylation of rhodopsin. Isoelectric focusing followed by Western blot analysis of bleached isolated retinae showed little dephosphorylation of rhodopsin for up to 4 h in darkness, even under conditions when rhodopsin was completely regenerated. Microspectrophotometeric determinations of rhodopsin spectra show that regenerated phospho-rhodopsin has the same molecular photosensitivity as unphosphorylated rhodopsin and that flash responses measured by trans-retinal electroretinogram or single-cell suction electrode recording displayed dark-adapted kinetics. Single quantal responses displayed normal dark-adapted kinetics, but rods were only half as sensitive as those containing exclusively unphosphorylated rhodopsin. We propose a model in which light-exposed retinae contain a mixed population of phosphorylated and unphosphorylated rhodopsin. Moreover, complete dark adaptation can only occur when all rhodopsin has been dephosphorylated, a process that requires >3 h in complete darkness. SIGNIFICANCE STATEMENT G-protein-coupled receptors (GPCRs) constitute the largest superfamily of proteins that compose ∼4% of the mammalian genome whose members share a common membrane topology. Signaling by GPCRs regulate a wide variety of physiological processes, including taste, smell, hearing, vision, and cardiovascular, endocrine, and reproductive homeostasis. An important feature of GPCR signaling is its timely termination. This normally occurs when, after their activation, GPCRs are rapidly phosphorylated by specific receptor kinases and subsequently bound by cognate arrestins. Recovery of receptor sensitivity to the ground state then requires dephosphorylation of the receptor and unbinding of arrestin, processes that are poorly understood. Here we investigate in mouse rod photoreceptors the relationship between rhodopsin dephosphorylation and recovery of visual sensitivity.
Treatment outcomes for HIV and MDR-TB co-infected adults and children: systematic review and meta-analysis.

BACKGROUND The incidence of multidrug-resistant tuberculosis (MDR-TB) is increasing in high human immunodeficiency virus (HIV) prevalence settings, with high associated mortality. Treatment outcomes in HIV-co-infected adults and children are poorly documented. OBJECTIVE To systematically assess treatment outcomes among HIV-MDR-TB co-infected patients. METHODS We searched two databases and the proceedings of an annual international conference up to November 2014 for studies reporting on major clinical outcomes among HIV-MDR-TB-co-infected adults and children, and pooled the results using random-effects meta-analysis. RESULTS Of 4812 abstracts and articles screened, 30 studies providing data on 2578 adults and 147 children were included. Overall pooled treatment success was 56.9% (95% confidence interval [CI] 46.2-67.6), 49.9% (95%CI 38.5-61.2) among adults and 83.4% (95%CI 74.7-92) among children. Mortality was 38% in adults (95%CI 28-48.1) and 11.4% (95%CI 5.8-17.1) in children. Loss to follow-up was higher among adults (16.1%, 95%CI 9-23.2) than among children (3.9%, 95%CI 0.9-6.9). Adverse events were experienced by the majority of patients; however, this was inconsistently documented. The use of fluoroquinolones, aminoglycosides and Group IV drugs appeared to be associated with treatment success. CONCLUSION The proportion of HIV-MDR-TB-co-infected patients achieving treatment success was similar to success rates reported among MDR-TB patients in general, regardless of HIV status; however, mortality was higher, particularly among adults, highlighting the need for early diagnosis and more effective treatment regimens.
A reticuloreticular commissural pathway in the rat thalamus

To further characterize the communication between the thalami of the two hemispheres, a connection linking the rostral reticular nuclei of the two thalamic sides was investigated in the rat by retrograde and anterograde tracing. The rostral reticular nucleus can be divided into a medial region, with densely packed fusiform neurons, and a lateral region, with less densely packed, polymorphic neurons. After injections of Fluorogold (FG) in the medial region, retrogradely labeled, small fusiform neurons were found in the corresponding contralateral region. The retrograde labeling data were confirmed by the anterograde‐tracing experiments. Thin, beaded axons, anterogradely labeled after injection of biocytin or biotinylated dextranamine in the medial region, innervate the corresponding region in the contralateral reticular nucleus.
Cell Cycle Regulation in Yeast

SUMMARY The development of P-protein (slime) in the phloem of Coleus stem apices has been studied electron microscopically using material fixed in glutaraldehyde followed by osmium tetroxide. In phloem parenchyma cells the earliest-appearing groups of tubular P-protein commonly are seen in close association with clusters of ' spiny' vesicles similar to those reported in Phaseolus phloem (Newcomb, 1967). The vesicles break down as the P-protein masses enlarge, and are assumed to contribute to P-protein formation. Subsequently the groups of tubules are consolidated into a single spindle-shaped body aligned longitudinally in each phloem parenchyma cell or sieve element. The microtubules observed frequently in the vicinity of the young P-protein body may play a role in its consolidation or in the longitudinal alignment of its constituent tubules. Some P-protein bodies acquire a highly organized structure in which the tubules are arranged hexagonally around lightly staining centres. Disaggregation of the P-protein body occurs during disintegration of the cytoplasm and nucleus, and results initially in the presence of swirls of packed fibrils. During disaggregation, the tubules of the mature P-protein body, which are about 200 A in diameter, are converted to fibrils about 70 A in diameter in a process apparently with several intermediate stages. In longitudinal view the fibrils exhibit alternate electron transparent and dense bands that impart a striated appearance to the mass. During maturation of the sieve element the swirls of fibrillar masses separate into individual fibrils which become dispersed through the cell lumen.
Modeling Ischemia-Induced Dyssynchronous Myocardial Contraction

Left ventricular (LV) contraction dyssynchrony is not easily quantified. We previously described a model for quantifying LV dyssynchrony that referenced regional amplitude and phase angles to global LV systole using esmolol-induced regional dyskinesis. We tested the hypothesis that our sine wave model and phase angle analysis of regional dyssynchrony in a canine model could also assess dyssynchrony of contraction during regional ischemia. Hence we compared intracoronary esmolol and matched regional ischemia in 10 anesthetized open-chest dogs. Regional and total LV volumes (conductance catheter), piezoelectric crystal shortening, and LV pressures were measured before, during, and after esmolol-induced apical dyskinesis and matched regional ischemia. We defined regional phase angle of contraction (&agr;) as the relative distance, measured in degrees, that regional minimal volume differed from global end-systole. We also compared maximal stroke volume (SV), observed effective SV (that portion of regional SV contributing to total SV for each treatment), and calculated effective SV (total regional SV × cosine &agr;). Dobutamine infusion increased homogeneity of regional &agr; relative to baseline. Both esmolol and ischemia significantly delayed (P < 0.05) apical contraction as quantified by increased &agr; (12.4° ± 28.1° to 27.4° ± 30.4° and 54.2° ± 32.6°, respectively) (mean ± sd) and decreased regional effective SV (4.7 ± 2.5 mL to 3.6 ± 2.2 mL and 4 ± 2.5 mL, respectively) relative to baseline. Our study indicates that intracoronary esmolol and ischemia induced qualitatively similar mechanical effects on myocardial function and that a sine wave model to estimate regional effective SV is a sensitive method to detect and quantify regional dyssynchrony induced by ischemia. Potentially, phase angle and regional amplitude analyses may prove to be effective measures to identify and quantify the beneficial effects of resynchronization therapies on myocardial function.
Interaction Between the Glutamine Cycle and the Uptake of Large Neutral Amino Acids in Astrocytes

Abstract: When astrocyte cultures are incubated with glutamate and ammonium, the clearance of these substrates followed by the formation and export of glutamine simulates the action of the “glutamine cycle” that is believed to function in the CNS. In the present study this process was found to increase the uptake of large neutral amino acids (LNAAs), namely, histidine, kynurenine, leucine, phenylalanine, and tryptophan, by two‐to threefold in mouse cerebral astrocytes. The enhancement of kynurenine uptake was shown to depend on the formation of glutamine and to saturate at low levels of glutamine. LNAAs transiently lowered the glutamine content of astrocytes that were incubated with glutamate and ammonium, but they did not affect net export of glutamine to the solution at normal physiological pH. However, on adjustment of the pH of the solution to 7.8, which causes a large increase in glutamine content without affecting export, kynurenine now significantly increased net glutamine export. These findings relate to proposed mechanisms of cerebral dysfunction in hyperammonemia.
Brain training in older adults: Evidence of transfer to memory span performance and pseudo-Matthew effects

ABSTRACT In this study the effects of ‘brain training’ using the Nintendo DS Brain Training program were examined in two groups of older adults; the cognitive performance of an experimental group (n = 21) who were asked to use the Nintendo DS regularly over a 6-week period was compared with the control group (n = 20). Groups were matched on age (mean age = 74 years), education, computer experience, daily activities (time spent reading or watching television), and initial scores of Wechsler Adult Intelligence Scale. Analyses revealed that improvements were primarily in the Digit Span Test, specifically Digits Backwards. Although the Brain Training package appeared to have some efficacy, other factors such as perceived quality of life and perceived cognitive functioning were at least equally important in determining training outcomes. The implications of these findings for cognitive training are discussed.
Optimization of cytokine stability in stored amniotic fluid.

OBJECTIVE Many studies use stored amniotic fluid samples to assay cytokines and other proteins for outcome-based research; however, there is little information on the optimal methods of storage. The objective of our study was to evaluate cytokine stability in amniotic fluid stored at different temperatures both with and without a proteolytic enzyme inhibitor. STUDY DESIGN Patients undergoing midtrimester genetic amniocentesis for routine indications gave consent for the study. After the sample was centrifuged, the acellular portion of the sample was mixed to homogeneity and aliquoted in 0.5-mL increments and stored for 1 year at 4 degrees C, -20 degrees C, and -80 degrees C with and without the protease inhibitor aprotinin. Enzyme-linked immunoassays for angiogenin, interleukin-6, and vascular endothelial growth factor were performed simultaneously on each aliquot. RESULTS Thirty samples were assayed for each storage condition. Results were calculated as the percentage of its own sister aliquot stored at -80 degrees C without aprotinin. In all samples, there was a significant relation between storage temperature and cytokine levels, with the lowest levels found at 4 degrees C and the highest at -80 degrees C (angiogenin, P =.004; interleukin-6, P <.001; vascular endothelial growth factor, P =.02). The addition of aprotinin improved stability only for angiogenin at all temperatures (all P <.05). CONCLUSIONS Degradation of cytokines occurs when amniotic fluid samples are stored for prolonged periods at temperatures greater than -80 degrees C. The addition of a protease inhibitor helps stem the degradation of some cytokines.
Osteonecrosis: The perils of steroids. A review of the literature and case report

Non-traumatic osteonecrosis is a cause of joint pain and deformity, not uncommonly caused by corticosteroid use. Despite this, corticosteroid induced osteonecrosis is poorly represented in the literature. We performed a detailed review of corticosteroid induced osteonecrosis, including aetiology, prevention, screening, clinical presentation, investigations, staging systems and treatment. We present this in the context of a patient at our institution who developed bilateral hip, shoulder and knee osteonecrosis following high dose corticosteroid therapy for dermatomyositis.
Potential of CF3I gas mixture as an insulation medium in gas-insulated equipment

SF6 is a widely used gas medium in gas-insulated equipment. Due to the high global warming potential and long atmospheric lifetime of SF6, there has been research into a new environmentally friendly replacement gas. This paper describes the research carried out at Cardiff University on CF3I gas and its mixture as a substitute insulation medium for SF6 in gas-insulated lines (GIL). A reduced-scale coaxial test system having the electric field properties of a full-scale 400 kV GIL system was fabricated. The design of the reduced-scale coaxial test system was simulated to ensure that the highest electric field would be along the center of the conductor. The coaxial prototype was then tested under a standard lightning impulse (1.2/50) in order to determine the 50% breakdown voltage for such a system when insulated with CF3I gas mixture. It was found that CF3I has the potential to replace SF6 as an insulation medium in GIL. A full-scale short length GIL demonstrator is being assembled in the laboratory to evaluate further the feasibility of using a CF3I gas mixture as an insulation medium.
Biological variability of particle deposition in the human respiratory tract during controlled and spontaneous mouth-breathing.

Total particle deposition in the respiratory tract of 20 subjects was experimentally determined for both controlled and spontaneous steady mouth-breathing of uncharged monodisperse aerosols in the diameter range 0.5 to 7.5 μm. A small intrasubject but a large intersubject variability of deposition was found. For spontaneous breathing the intersubject variability of deposition is determined by morphological factors but the intersubject variability of deposition rate by physiological factors.
Emodin reverses leukemia multidrug resistance by competitive inhibition and downregulation of P-glycoprotein

Development of multidrug resistance (MDR) is a continuous clinical challenge partially due to the overexpression of P-glycoprotein (P-gp) for chronic myelogenous leukemia (CML) patients. Herein, we evaluated the inhibitory potency of emodin, a natural anthraquinone derivative isolated from Rheum palmatum L, on P-gp in P-gp positive K562/ADM cells. Competition experiments combined with molecular docking analysis were utilized to investigate the binding modes between emodin and binding sites of P-gp. Emodin reversed adriamycin resistance in K562/ADM cells accompanied with the decrease of P-gp protein expression, further increasing the uptake of rhodamine123 in both K562/ADM and Caco-2 cells, indicating the inhibition of P-gp efflux function. Moreover, when incubated with emodin under different conditions where P-gp was inhibited, K562/ADM cells displayed increasing intracellular uptake of emodin, suggesting that emodin may be the potential substrate of P-gp. Importantly, rhodamine 123 could increase the Kintrinsic (Ki) value of emodin linearly, whereas, verapamil could not, implying that emodin competitively bound to the R site of P-gp and noncompetition existed between emodin and verapamil at the M site, in a good accordance with the results of molecular docking that emodin bound to the R site of P-gp with higher affinity. Based on our results, we suggest that emodin might be used to modulate P-gp function and expression.
STUDIES ON THE VITAMIN D 3 REQUIREMENT OF THE BROILER CHICK.

Abstract THE vitamin D3 requirement of the growing chick has been estimated by the National Research Council (1960) to be 90 I.C. U. per pound of feed. Recent studies by Waldroup et al. (1963b) indicated that dietary vitamin D3 levels of 360 I.C. U. per pound increased body weight and percent bone ash. However, the response to higher levels of this vitamin became less as calcium and phosphorus levels approached optimum. To gain additional information regarding the effect of increased vitamin D3 levels and the relationship of this vitamin to the calcuim and phosphorus content of the diet, three experiments were conducted under conditions of practical-type rearing as well as in battery brooders isolated from sources of ultraviolet light. MATERIALS AND METHODS Battery brooder studies—A factorial arrangement with two calcium levels (0.50 and 1.00 percent), two phosphorus levels (0.50 and 0.70 percent total phosphorus) and seven levels of vitamin D3 was used. …
Evidence of resilience in families of children with autism.

BACKGROUND Family resilience is a growing field of inquiry, investigating factors that contribute to a family's becoming stronger in spite of dealing with adversity. Despite the growing interest in studying family resilience, the topic has not been explored in families with children who have disabilities. This report, a part of a larger study--using both quantitative and qualitative methodologies--is an examination of factors of family resilience in the families of children with autism. Evidence of family resilience such as family connectedness and closeness, positive meaning-making of the disability, and spiritual and personal growth were identified and examined in this part of the study. METHOD The study uses a survey methodology, analysing responses to several rating scales and written responses to three open-ended questions. Survey respondents consisted of 175 parents and other primary caregivers of a child with autism--ages between 2 and 18 years. RESULTS Results suggest identification of specific resilience processes, such as: making positive meaning of disability, mobilization of resources, and becoming united and closer as a family; finding greater appreciation of life in general, and other people in specific; and gaining spiritual strength. CONCLUSIONS This study presents evidence that a considerable number of families of children with autism display factors of resilience--reporting having become stronger as a result of disability in the family.
Dual identity among immigrants: Comparing different conceptualizations, their measurements, and implications.

OBJECTIVES This article aims to make a contribution to the literature by comparing 3 existing and often used conceptualizations and measurements of immigrants' dual identity: (a) high levels of identification with separate ethnic and national identities (Studies 1 and 2), (b) dual self-identification (Study 1), and (c) the strength of dual identification (Study 2). METHOD Large-scale survey data are used in 2 studies, capturing 6 recent immigrant groups (Afghanis, Chinese, Iranians, Iraqis, Polish, and Somalis; Study 1, N = 5,877) and immigrants from Turkey (Study 2, N = 427) to The Netherlands. We investigate the associations between the different measures of dual identity as well as how each relates to indicators of intergroup relations (perceived subgroup respect and perceived discrimination) and immigrants' psychological outcomes (feeling at home in The Netherlands, happiness, affect toward the Dutch). RESULTS The findings show that dual self-identification differs most markedly from high identification on separate ethnic and national identities. The latter conceptualization largely overlaps with the strength of dual identification, both in terms of the classification of who is a dual identifier, as well as the associations with intergroup relations and immigrants' psychological outcomes. CONCLUSIONS These findings help to clarify discrepant approaches to dual identity in the existing literature and provide guidelines for future research into dual identity among immigrants in Western societies. In particular, they suggest that a distinction between dual self-identification and measures of group identification is needed.
Evidence for non‐cholinergic, non‐adrenergic nervous control of mucus secretion into the cat trachea.

We have investigated the effects of electrical stimulation of the vagus nerves on the output of mucus glycoproteins (mucins), radiolabelled with 3H and 35S, into the trachea of anaesthetized cats. In five control experiments, stimulation of the vagus nerves on four successive occasions, separated by 1 h, caused significant rises in the output of radiolabelled mucins. In these experiments repetition of stimulation did not appear to lessen the response. In a parallel series of five experiments the vagus nerves were again stimulated on four occasions, but atropine was administered in increasing doses between the stimuli. Large responses, not significantly less than those seen in the corresponding control stimulations, were seen even in the presence of the highest dose of atropine. In this series of experiments, however, the effect of the last vagal stimulation (with the highest dose of atropine) was significantly less then the first (no atropine). Administration of phentolamine and l‐propranolol in addition to atropine failed to reduce the response to vagal stimulation significantly. We conclude that, while cholinergic nerves can probably explain part of the increase in mucin output which occurs with vagus nerve stimulation, there is a large response mediated by a non‐cholinergic, non‐adrenergic neurotransmitter. Possible neurotransmitters and the relationship of these findings to those of earlier studies are discussed.