Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunologic and structural analysis of eight novel domain‐deletion β3 integrin peptides designed for detection of HPA‐1 antibodies

Summary. Background: The single‐nucleotide polymorphism (SNP) rs5918 in the ITGB3 gene defines the human platelet antigen‐1 (HPA‐1) system encoding a Leu (HPA‐1a) or Pro (HPA‐1b) at position 33. HPA‐1 antibodies are clinically the most relevant in the Caucasoid population, but detection currently requires αIIbβ3 integrin from the platelets of HPA‐genotyped donors.Objectives: We set out to define the β3 integrin domains required for HPA‐1a antibody binding and produce recombinant soluble β3 peptides for HPA‐1 antibody detection.Methods: We designed two sets (1a and 1b) of four soluble β3 domain‐deletion peptides (ΔSDL, ΔβA, PSIHybrid, PSI), informed by crystallography studies and computer modeling. The footprints of three human HPA‐1a‐specific phage antibodies were defined by analyzing binding patterns to the β3 peptides and canine platelets, and models of antibody–antigen interfaces were derived. Specificity and sensitivity for HPA‐1a detection were assessed using sera from 140 cases of fetomaternal alloimmune thrombocytopenia (FMAIT). Results: Fusion of recombinant proteins to calmodulin resulted in high‐level expression in Drosophila S2 cells of all eight β3 peptides. Testing of FMAIT samples indicated that ΔβA‐Leu33 is the superior peptide for HPA‐1a antibody detection, with 96% sensitivity and 95% specificity. The existence of type I and II categories of HPA‐1a antibodies was confirmed by the study of HPA‐1a phage antibody footprints and the reactivity pattern of clinical samples with the four β3‐Leu33 peptides, but there was no correlation between antibody category and clinical severity of FMAIT. Conclusions: Soluble recombinant β3 peptides can be used for detection of clinical HPA‐1a antibodies.
Genotoxicity of Poorly Soluble Particles

Poorly soluble particles such as TiO2, carbon black, and diesel exhaust particles have been evaluated for their genotoxity using both in vitro and in vivo assays, since inhalation of these compounds by rats at high concentrations has been found to lead to tumor formation. Two principle modes of genotoxic action can be considered for particles, referred to as primary and secondary genotoxicity. Primary genotoxicity is defined as genetic damage elicited by particles in the absence of pulmonary inflammation, whereas secondary genotoxicity implies a pathway of genetic damage resulting from the oxidative DNA attack by reactive oxygen/nitrogen species (ROS/RNS), generated during particle-elicited inflammation. Conceptually, primary genotoxicity might operate via various mechanisms, such as the actions of ROS (e.g., as generated from reactive particle surfaces), or DNA–adduct formation by reactive metabolites of particle-associated organic compounds (e.g., polycyclic aromatic hydrocarbons). Currently available literature data, however, merely indicate that the tumorigenesis of poorly soluble particles involves a mechanism of secondary genotoxicity. However, further research is urgently required, since (1) causality between pulmonary inflammation and genotoxicity has not yet been established, and (2) effects of inflammation on fundamental DNA damage responses that orchestrate mutagenesis and carcinogenic outcome,that is, cell cycle arrest, DNA repair, proliferation, and apoptosis, are currently poorly understood.
Monitoring of implanted stem cell migration in vivo: A highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat

In vivo monitoring of stem cells after grafting is essential for a better understanding of their migrational dynamics and differentiation processes and of their regeneration potential. Migration of endogenous or grafted stem cells and neurons has been described in vertebrate brain, both under normal conditions from the subventricular zone along the rostral migratory stream and under pathophysiological conditions, such as degeneration or focal cerebral ischemia. Those studies, however, relied on invasive analysis of brain sections in combination with appropriate staining techniques. Here, we demonstrate the observation of cell migration under in vivo conditions, allowing the monitoring of the cell dynamics within individual animals, and for a prolonged time. Embryonic stem (ES) cells, constitutively expressing the GFP, were labeled by a lipofection procedure with a MRI contrast agent and implanted into rat brains. Focal cerebral ischemia had been induced 2 weeks before implantation of ES cells into the healthy, contralateral hemisphere. MRI at 78-μm isotropic spatial resolution permitted the observation of the implanted cells with high contrast against the host tissue, and was confirmed by GFP registration. During 3 weeks, cells migrated along the corpus callosum to the ventricular walls, and massively populated the borderzone of the damaged brain tissue on the hemisphere opposite to the implantation sites. Our results indicate that ES cells have high migrational dynamics, targeted to the cerebral lesion area. The imaging approach is ideally suited for the noninvasive observation of cell migration, engraftment, and morphological differentiation at high spatial and temporal resolution.
The Senior Psychiatrist Survey III: Attitudes Towards Personal Ageing, Life Experiences and Psychiatric Practice

Objective: The aim of this study is: to explore whether there is a relationship between the effects of gender, age and perceptions of personal health on psychiatrist's reactions to personal ageing; and to determine the effects of psychiatrist's reactions to personal ageing upon their approach to clinical practice, retirement planning and post-retirement activities. Method: A postal survey was conducted. Respondents were Fellows of the Royal Australian and New Zealand College of Psychiatrists resident in Australia or New Zealand. Of 1086 eligible subjects, 529 participated. The main outcome measures were: Reactions to Ageing Questionnaire (RAQ); self-rated health; location and type of psychiatric practice; the perceived benefits and drawbacks of age on psychiatric practice and case selection; and retirement plans. Results: Positive attitudes towards personal ageing were significantly associated with old age, males and good or excellent self-rated health. Negative attitudes were associated with working in universities and anticipated retirement due to poor health. Field of practice, anticipated post-retirement activities and approach to clinical practice were not found to have a significant effect on attitudes towards personal ageing. Conclusions: The effects of life experiences on psychiatrists' attitudes towards personal ageing are complex. Attitudes towards personal ageing have little impact on psychiatric practice.
Genetic variability of hepatitis C virus non‐structural protein 3 and virus‐specific CD8+ response in patients with chronic hepatitis C

Hepatitis C virus (HCV) variation in specific T‐cell epitopes may represent a mechanism of viral persistence in chronic infection. We examined the HCV non‐structural protein 3 (NS3), including the immunologically relevant epitopes HCV NS3‐2 KLVALGINAV (human leukocyte antigen [HLA]‐A2‐restricted) and HCV NS3‐1391 LIFCHSKKK (HLA‐A3‐restricted), in 22 HLA‐A2+ patients with chronic infection. Significant amino acid variation was found in HCV NS3‐2 epitope sequences when compared to the HCV‐1 prototype virus. Six of the nine different HCV NS3‐2 peptide variants were identified in patients with HCV NS3‐2‐specific CD8+ cells, detected with an HLA‐A2 tetramer made with the HCV‐1 prototype peptide. Phylogenetic analysis, including HCV reference sequences other than HCV‐1, suggested however that most of the variations in the HCV NS3‐2 epitope could be related to genetic heterogeneity between HCV reference subtypes. Variation was less common when comparing HCV NS3‐2 epitope sequences from the clinical isolates to the most‐closely related HCV reference subtype in each case. Some subtype‐independent variations were found in epitopic residues probably important for T‐cell receptor interaction. In contrast, no significant variation was found in HLA primary anchor sites, flanking regions, or in the contiguous HLA A3‐restricted CD8+ T‐cell epitope. Ongoing variation was not evident in two selected patients with follow‐up. In conclusion, (i) the HCV NS3‐2 epitope is not conserved between different HCV strains/subtypes, and (ii) an HLA‐A2 tetramer loaded with the HCV‐1 prototype NS3‐2 peptide may still detect NS3‐specific CD8+ cells in some patients with variant viruses. These data may be useful to improve T‐cell assays using HCV NS3 peptides, taking into account the genetic diversity of this virus. J. Med. Virol. 72:575–585, 2004. © 2004 Wiley‐Liss, Inc.
When Does False-Belief Understanding Emerge ?

Intense controversy surrounds the question of when children first understand that others can hold false beliefs. Results from traditional tasks suggest that false-belief understanding does not emerge until about 4 years of age and constitutes a major developmental milestone in social cognition. By contrast, results from nontraditional tasks, which have steadily accumulated over the past 10 years, suggest that false-belief understanding is already present in infants (under age 2 years) and toddlers (age 2–3 years) and thus forms an integral part of social cognition from early in life. Here we first present an overview of the findings from nontraditional tasks. We then return to traditional tasks and argue that processing difficulties, rather than limitations in false-belief understanding, account for young children’s failure at these tasks.
Use of anhydrous calcium phosphate and selected binders in the tablet formulation of a deliquescent crude plant extract: Vernonia galamensis (Asteraceae)

In this study, the effect of anhydrous calcium phosphate, an efflorescent pharmaceutical powder of reduced moisture content, ideal for moisture-sensitive materials; and the comparative binding effects of maize starch, polyvinylpyrrolidone and gelatin were investigated in the tablet formulation of the deliquescent crude extract of the leaves of Vernonia galamensis (Asteraceae). Materials used include; anhydrous calcium phosphate (BDH chemicals Ltd. Poole, England), maize starch and gelatin (May and Baker, Germany). Granule and tablet analyses were carried out according to standard procedures in the BP 2007. Preparations of the binders at varying concentrations of 2.5, 5.0 and 7.5% w/v were used to produce the granules by wet granulation method and compressed into tablets at 26.25KN. The mechanical strengths and drug release properties of the designed tablets were assessed using the crushing strengthfriability, disintegration time ratio (CSFR:DT) and dissolution rate. An increase in binder concentration led to an increase in crushing strength, decrease in friability and increase in disintegration time of the tablets. Anhydrous calcium phosphate used as diluent along with polyvinylpyrrolidone as binder produced the best quality tablets in terms of the CSFR: DT ratio and dissolution rate as compared to the diluent used with maize starch and gelatin as binders.
Plasminogen activator inhibitor‐1 regulates macrophage‐dependent postoperative adhesion by enhancing EGF‐HER1 signaling in mice

Adhesive small bowel obstruction remains a common problem for surgeons. After surgery, platelet aggregation contributes to coagulation cascade and fibrin clot formation. With clotting, fibrin degradation is simultaneously enhanced, driven by tissue plasminogen activator–mediated cleavage of plasminogen to form plasmin. The aim of this study was to investigate the cellular events and proteolytic responses that surround plasminogen activator inhibitor (PAI‐1; Serpine1) inhibition of postoperative adhesion. Peritoneal adhesion was induced by gauze deposition in the abdominal cavity in C57BL/6 mice and those that were deficient in fibrinolytic factors, such as Plat−/− and Serpine1−/−. In addition, C57BL/6 mice were treated with the novel PAI‐1 inhibitor, TM5275. Some animals were treated with clodronate to deplete macrophages. Epidermal growth factor (EGF) experiments were performed to understand the role of macrophages and how EGF contributes to adhesion. In the early phase of adhesive small bowel obstruction, increased PAI‐1 activity was observed in the peritoneal cavity. Genetic and pharmacologic PAI‐1 inhibition prevented progression of adhesion and increased circulating plasmin. Whereas Serpine1−/− mice showed intra‐abdominal bleeding, mice that were treated with TM5275 did not. Mechanistically, PAI‐1, in combination with tissue plasminogen activator, served as a chemoattractant for macrophages that, in turn, secreted EGF and up‐regulated the receptor, HER1, on peritoneal mesothelial cells, which led to PAI‐1 secretion, further fueling the vicious cycle of impaired fibrinolysis at the adhesive site. Controlled inhibition of PAI‐1 not only enhanced activation of the fibrinolytic system, but also prevented recruitment of EGF‐secreting macrophages. Pharmacologic PAI‐1 inhibition ameliorated adhesion formation in a macrophage‐dependent manner. —Honjo, K. , Munakata, S. , Tashiro, Y. , Salama, Y. , Shimazu, H. , Eiamboonsert, S. , Dhahri, D. , Ichimura, A. , Dan, T. , Miyata, T. , Takeda, K. , Sakamoto, K. , Hattori, K. , Heissig, B. Plasminogen activator inhibitor‐1 regulates macrophage‐dependent postoperative adhesion by enhancing EGF‐HER1 signaling in mice. FASEB J. 31, 2625–2637 (2017). www.fasebj. org
Inhibition of Toll-like receptor 4 breaks the inflammatory loop in autoimmune destructive arthritis.

OBJECTIVE Degeneration of extracellular matrix of cartilage leads to the production of molecules capable of activating the immune system via Toll-like receptor 4 (TLR-4). The objective of this study was to investigate the involvement of TLR-4 activation in the development and progression of autoimmune destructive arthritis. METHODS A naturally occurring TLR-4 antagonist, highly purified lipopolysaccharide (LPS) from Bartonella quintana, was first characterized using mouse macrophages and human dendritic cells (DCs). Mice with collagen-induced arthritis (CIA) and mice with spontaneous arthritis caused by interleukin-1 receptor antagonist (IL-1Ra) gene deficiency were treated with TLR-4 antagonist. The clinical score for joint inflammation, histologic characteristics of arthritis, and local expression of IL-1 in joints were evaluated after treatment. RESULTS The TLR-4 antagonist inhibited DC maturation induced by Escherichia coli LPS and cytokine production induced by both exogenous and endogenous TLR-4 ligands, while having no effect on these parameters by itself. Treatment of CIA using TLR-4 antagonist substantially suppressed both clinical and histologic characteristics of arthritis without influencing the adaptive anti-type II collagen immunity crucial for this model. Treatment with TLR-4 antagonist strongly reduced IL-1beta expression in articular chondrocytes and synovial tissue. Furthermore, such treatment inhibited IL-1-mediated autoimmune arthritis in IL-1Ra(-/-) mice and protected the mice against cartilage and bone pathology. CONCLUSION In the present study, we demonstrate for the first time that inhibition of TLR-4 suppresses the severity of experimental arthritis and results in lower IL-1 expression in arthritic joints. Our data suggest that TLR-4 might be a novel target in the treatment of rheumatoid arthritis.
Empowerment as Treatment and the Role of Health Professionals

This article argues that the concept of empowerment has been co-opted by health professionals and redefined as an intervention to produce compliance. Patients are considered empowered by health professionals only if they make the correct choices as defined by the health care provider. Patients are not informed about all possible choices and are not free to make their own choices for their own reasons. Empowerment is a coercive strategy that is justified by its outcomes and creates dependent populations.
Serum cholesterol and lipid peroxidation are decreased by melatonin in diet‐induced hypercholesterolemic rats

The purpose of this study was to investigate the effect of melatonin, at pharmacological doses, on serum lipids of rats fed with a hypercholesterolemic diet. Therefore, different groups of animals were fed with either the regular Sanders Chow diet or a diet enriched in cholesterol. Moreover, animals were treated with or without melatonin in the drinking water for 3 months. We show that melatonin treatment did not affect the levels of cholesterol or triglycerides in rats fed with a regular diet. However, the increase in total cholesterol and low‐density lipoprotein (LDL)‐cholesterol induced by a cholesterol‐enriched diet was reduced significantly by melatonin administration. On the other hand, melatonin administration prevented the decrease in high‐density lipoprotein (HDL)‐cholesterol induced by the same diet. No differences in the levels of very low‐density lipoprotein (VLDL)‐cholesterol and triglycerides were found. We also found that melatonin administration slightly decreased serum uric, bilirubin and increased serum glucose levels. Other biochemical parameters, including total proteins, creatinine, urea, phosphorus, calcium, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), Γ‐glutamyltranspeptidase (Γ‐GT), acetyl cholinesterase (AcCho), and alkaline phosphatase (ALP) were not modified by melatonin treatment. Finally, lipid peroxidation (LPO) was studied in membranes of liver, brain, spleen, and heart as an index of membrane oxidative damage. Results show that hypercholesterolemic diet did not modify the LPO status in any of the tissues studied. However, chronic melatonin administration significantly decreased LPO. Results confirm that melatonin participates in the regulation of cholesterol metabolism and in the prevention of oxidative damage to membranes.
Mechanism of lethal action of 2,450-MHz radiation on microorganisms

Various bacteria, actinomycetes, fungi, and bacteriophages were exposed to microwaves of 2,450 +/- 20 MHz in the presence and in the absence of water. It was found that microorganisms were inactivated only when in the presence of water and that dry or lyophilized organisms were not affected even by extended exposures. The data presented here prove that microorganisms are killed by "thermal effect" only and that, most likely, there is no "nonthermal effect"; cell constituents other than water do not absorb sufficient energy to kill microbial cells.
Feedback Blunting: Total Sleep Deprivation Impairs Decision Making that Requires Updating Based on Feedback.

STUDY OBJECTIVES To better understand the sometimes catastrophic effects of sleep loss on naturalistic decision making, we investigated effects of sleep deprivation on decision making in a reversal learning paradigm requiring acquisition and updating of information based on outcome feedback. DESIGN Subjects were randomized to a sleep deprivation or control condition, with performance testing at baseline, after 2 nights of total sleep deprivation (or rested control), and following 2 nights of recovery sleep. Subjects performed a decision task involving initial learning of go and no go response sets followed by unannounced reversal of contingencies, requiring use of outcome feedback for decisions. A working memory scanning task and psychomotor vigilance test were also administered. SETTING Six consecutive days and nights in a controlled laboratory environment with continuous behavioral monitoring. SUBJECTS Twenty-six subjects (22-40 y of age; 10 women). INTERVENTIONS Thirteen subjects were randomized to a 62-h total sleep deprivation condition; the others were controls. MEASUREMENTS AND RESULTS Unlike controls, sleep deprived subjects had difficulty with initial learning of go and no go stimuli sets and had profound impairment adapting to reversal. Skin conductance responses to outcome feedback were diminished, indicating blunted affective reactions to feedback accompanying sleep deprivation. Working memory scanning performance was not significantly affected by sleep deprivation. And although sleep deprived subjects showed expected attentional lapses, these could not account for impairments in reversal learning decision making. CONCLUSIONS Sleep deprivation is particularly problematic for decision making involving uncertainty and unexpected change. Blunted reactions to feedback while sleep deprived underlie failures to adapt to uncertainty and changing contingencies. Thus, an error may register, but with diminished effect because of reduced affective valence of the feedback or because the feedback is not cognitively bound with the choice. This has important implications for understanding and managing sleep loss-induced cognitive impairment in emergency response, disaster management, military operations, and other dynamic real-world settings with uncertain outcomes and imperfect information.
A user-centered design approach in the development of rehabilitation devices after stroke

Involving users in iterative development processes is to be shown to increase the quality of health care devices and to prevent refusal. Successful use can only be achieved provided that the devices are accepted by its users. In this study potentials of user satisfaction surveys in the development of stroke rehabilitation devices are presented. The two arm-training devices Reha-Slide (RS) and Bi-Manu-Track (BMT) are assessed for patient satisfaction. The aim is to detect the satisfaction with the current state of certain aspects of the devices to obtain incentives for technical optimisation. Correlation analyses from the data of 18 patients show significant positive correlations between satisfaction with the introduction and the personal well-being during training with both devices, whereas no significant correlations are found between satisfaction with the introduction and the perceived safety. In the RS sample, a higher satisfaction with the training also correlates with a higher feeling of improvement. The results are used to derive improvement suggestions tailored to the systems and its users. The surveys are conducted as a method for improving the ongoing design process of innovative technical devices developed in the BMBF (Federal Ministry of Education and Research) funded project “BeMobil”.
A Bacteroides thetaiotaomicron outer membrane protein that is essential for utilization of maltooligosaccharides and starch

Previous studies suggested that the first step in utilization of starch by Bacteroides thetaiotaomicron was binding of the polysaccharide to the cell surface, followed by translocation of the polysaccharide across the outer membrane into the periplasm. In this study, we report the molecular characterization of a gene that encodes an outer membrane protein that is essential for utilization of both maltooligosaccharides and starch. The gene, susC, encoded a protein of 115.3 kDa. Antibodies were raised against SusC, and the outer membrane location of SusC could be confirmed by Western blot (immunoblot) analysis. SusC had a possible signal sequence of between 20 and 39 amino acids, depending on which N-terminal methionine initiates the start of the protein. It also had some features typical of well-characterized outer membrane proteins from members of the family Enterobacteriaceae, such as a terminal phenylalanine residue and a region in the amino portion of the protein thought to be involved in stabilizing the protein in the outer membrane. The amino acid sequence, together with results of gene disruption experiments, suggested that SusC was not an amylolytic enzyme. Transcriptional fusion experiments, using beta-glucuronidase as a reporter group, showed that expression of susC was maltose regulated at the transcriptional level. This is the first molecular characterization of a B. thetaiotaomicron outer membrane protein involved in maltooligosaccharide and starch utilization.