Miracle-dz/UniFAR-FTUs huggingface dataset:
Deviation of immune response to Chlamydia psittaci outer membrane protein in lipopolysaccharide-hyporesponsive mice

The outcome of infection is determined by both the quantity and the quality of an induced immune response. In particular, it has been demonstrated for selected pathogens that induction of TH1 or TH2 type helper T-cell subsets determines whether an immune response gives rise to protective immunity or disease-associated immunopathology. The nature of the antigen and the type of antigen-presenting cells recruited in the induction of a response are critical factors that influence the quality of the immune response. Of particular interest in this respect is the immune response to bacterial particles and the impact of cell wall-associated lipopolysaccharide (LPS) on that response. Nonspecific activation of macrophages and B lymphocytes by LPS could skew the phenotype of activated antigen-presenting cells and selectively alter the immunoglobulin isotypes and helper T-cell subsets that are induced following infection. In an initial attempt to detect immune deviation associated with LPS stimulation, we have compared the immunoglobulin isotypes of antibodies specific for the cysteine-rich outer membrane protein Omp2 induced in normal and LPS-hyporesponsive mice following immunization with Chlamydia psittaci strain guinea pig inclusion conjunctivitis whole elementary bodies. We report that there is a dramatic shift of Omp2-specific antibody from predominantly immunoglobulin G2a (IgG2a) isotype in LPS-hyporesponsive mice to high levels of IgG1 isotype in LPS-responder strains. The dependence of the IgG1 isotype shift on the LPS responder status is linked to the structure of the antigen and its natural processing pathway since LPS-hyporesponsive mice are not, in general, deficient in IgG1 antibody production. In particular, the antibody response to purified recombinant Omp2 is predominantly of the IgG1 isotype even in LPS-hyporesponsive mice.
Processing of the Papain Precursor

The cysteine protease papain is synthesized as a 40-kDa inactive precursor with a 107-amino-acid N-terminal pro region. Although sequence conservation in the pro region is lower than in the mature proteases, a conserved motif (Gly-Xaa-Asn-Xaa-Phe-Xaa-Asp, papain precursor numbering) was found within the pro region of cysteine proteases of the papain superfamily. To determinate the function to this conserved motif, we have mutagenized at random each of the 4 residues individually within the pro region of the papain precursor. Precursor mutants were expressed in yeast, screened according to their ability to be processed through either a cis or trans reaction, into mature active papain. Three classes of mutants were found. Non-functional propapain mutants of the first class are completely degraded by subtilisin indicating that they are not folded into a native state. Mutants of the second class were neutral with respect to cis and trans processing. The third class included mutants that mostly accumulated as mature papain in the yeast vacuole. They had mutations that had lost the negatively charged Asp residues and a mutation that probably introduces a positive charge, PheHis. The precursor of the PheHis mutant could be recovered by expression in a vph1 mutant yeast strain which has a vacuolar pH of about 7. The PheHis propapain mutant has an optimum pH of autoactivation about one pH unit higher than the wild type molecule. These results indicate that the electrostatic status of the conserved motif participates in the control of intramolecular processing of the papain precursor.
Analysis of the p53 and MDM‐2 gene in acute myeloid leukemia

Abstract: The MDM‐2 (murine double minute 2) gene codes for a cellular protein that can bind to the p53 tumor suppressor gene product, thereby functioning as a negative regulator of p53. In order to define the role of the MDM‐2 gene in the pathogenesis of human acute myeloid leukemia, the expression and the sequence of the MDM‐2 gene were examined in samples of bone marrow and/or peripheral mononuclear cells of 38 patients by using immunostaining, polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing. Immunohistochemical staining detected a weak accumulation of the MDM‐2 protein in AML patients of FAB classification M4 and M5. RT‐PCR analysis revealed a heterogeneous expression pattern of MDM‐2 mRNA in AML samples of different FAB classification. An increased level of MDM‐2 mRNA expression was observed in 17 of 38 AML patients when compared to normal controls. No structural changes in a 488 bp region extending from nucleotide 890 to 1378 of the MDM‐2 cDNA were detected using RT‐SSCP and sequence analysis. In addition, heterogeneous expression of p53 transcripts was found with the highest p53 mRNA levels in AML M4 and M5. Interestingly, there seems to be a correlation between the relative ratios of p53 and MDM‐2 mRNA levels in AML M4 and M5: in 15 of 23 cases high p53 mRNA expression was directly associated with high levels of MDM‐2 transcripts. An exclusively intranuclear p53 immunostaining pattern was found in 10 of 16 (58%) AML FAB M4 and M5, whereas the remaining AML samples tested were negative for p53 (0/10). Using RT‐SSCP analysis and direct sequencing of the RT‐PCR amplification products of p53 exon 5–8, we observed that only 1 of 38 AML patients showed a point mutation in the p53 gene. This missense mutation occurred in the evolutionary highly conserved region of p53 at codon 255 (Ile to Phe). These data indicated that structural alterations of the p53 gene do not play an important role in the initiation and progression of AML. However, abrogation of p53 tumor suppressor function due to MDM‐2 overexpression may be an alternative molecular mechanism by which a subset of AMLs may escape from p53‐regulated growth control.
ESCRT (Endosomal Sorting Complex Required for Transport) Machinery Is Essential for Acrosomal Exocytosis in Human Sperm1

ABSTRACT The sperm acrosome reaction is a unique, regulated exocytosis characterized by the secretion of the acrosomal content and the release of hybrid vesicles formed by patches of the outer acrosomal and plasma membranes. In previous reports, we have shown that inward invaginations of the acrosomal membrane delineate ring-shaped membrane microdomains that contact the plasma membrane. We have postulated that the opening and expansion of fusion pores along these rings trigger acrosomal exocytosis. The invaginations of the acrosomal membrane topologically resemble the deformations of the endosomal membrane leading to the assembly of luminal vesicles in multivesicular bodies. In fact, intra-acrosomal vesicles are also formed during acrosomal exocytosis. Endosomal sorting complex required for transport (ESCRT) participates in the organization of membrane microdomains that are invaginated and released as intraluminal vesicles in endosomes. We report here that members of ESCRT I (TSG101), ESCRT III (CHMP4), and the AAA ATPase VPS4 are present in the acrosomal region of the human sperm. Perturbing the function of these factors with antibodies or recombinant proteins inhibited acrosomal exocytosis in permeabilized cells. A similar effect was observed with a dominant-negative mutant of VPS4A cross-linked to a cell-penetrating peptide in nonpermeabilized sperm stimulated with a calcium ionophore. When the function of ESCRTs was inhibited, acrosomes showed abnormal deformation of the acrosomal membrane, and SNARE proteins that participate in acrosomal exocytosis failed to be stabilized in neurotoxin-resistant complexes. However, the growing of membrane invaginations was not blocked, and numerous intra-acrosomal vesicles were observed. These observations indicate that ESCRT-mediated processes are essential for acrosomal secretion, implicating these multifunctional complexes in an exocytic event crucial for sperm-egg fusion.
Significance of altered bilirubin subfractions in bile following hepatectomy.

BACKGROUND Hyperbilirubinemia occurs as a sign of hepatic failure after hepatectomy. The pathogenesis of this event has not been elucidated. In cases complicated with postoperative infection, hyperbilirubinemia is prolonged and the composition of bilirubin subfractions in bile changes markedly. A reduction in the proportion of bilirubin diglucuronide (BDG) is especially notable. This study was aimed at clarifying the relationship between infection and biliary bilirubin subfractions, with a view to shedding light on the mechanisms of change. MATERIALS AND METHODS Rats underwent either laparotomy or partial hepatectomy (Hx). Daily intraperitoneal injections of lipopolysaccharide (LPS) or natural saline were administered for 3 days following surgery. Total serum bilirubin levels and proportions of BDG and bilirubin in bile were measured until Day 5 after the operation. Hepatic levels of UDP-glucuronic acid (UDP-GA), UDP-glucose, NAD(+), and total adenine nucleotides (TAN) and activities of UDP-glucuronyltransferase (UDP-GT) and UDP-glucose dehydrogenase were measured on Day 4. RESULTS In hepatectomized rats treated with LPS (Hx-LPS), total serum bilirubin levels were elevated, biliary bilirubin levels were decreased, and the proportion of biliary BDG was decreased on Day 4. Hepatic levels of UDP-GA, NAD(+), and TAN and activities of UDP-GT in Hx-LPS were reduced. In all groups tested, a significant linear correlation between BDG and UDP-GA and between UDP-GA and NAD(+) was found. CONCLUSIONS The reduction of UDP-GA might be effected by reduced hepatic levels of NAD(+) in endotoxemia following hepatectomy. It is therefore suggested that alterations in biliary bilirubin subfractions might accurately reflect the energy state of the remnant liver following hepatectomy.
The Impact of Global Financial Crisis on Informational Efficiency: Evidence from Price-Volume Relationship in Crude Palm Oil Futures Market

As a source of energy of biofuel and edible oil, the fluctuation of crude palm oil prices is the concern of producers and manufacturers. However, little is known about the impact of global financial crisis on informational efficiency of crude palm oil (CPO) futures market. Hence, this study aims to examine information spillover between the CPO futures price changes and volume during the pre-crisis, crisis and post-crisis periods. Result of augmented analysis provides three findings: First, in pre-crisis period, trading volume transmits information to return, in contrast return dominates this role in the post-crisis period. This asymmetric information flow supports the “heterogeneity of traders” hypothesis. Second, the volatility persistence of augmented model is relatively higher than univariate model during the post-crisis, this shows that informational efficiency has decreased after the crisis. Third, inconsistent time span observed in cross-correlation function also supports the noise traders’ hypothesis in the CPO futures market. This study observes that traders have acquired new behavior in the post-crisis period by relying on returns as the proxy of information flow.
Land use, planning, and the “difficult character of property”

Abstract Contemporary land use planning has an ambivalent relationship with private property. While inextricably entangled with private property, planning frequently presents itself as at a remove, such that planning does not appear to regulate property, but rather acts upon “land use. ” It is tempting to see land use, therefore, as a means by which planning can institutionally distance itself from its necessary relationship to private property. An original genealogy of land use planning within Canada, however, reveals its entanglement with debates concerning the governance of land, and the imperative for the state assessment of the productive or wasteful uses to which it is put. Private property thus emerges as a central concern to planning, given its importance to landholding, the fear being that unregulated private property leads to unproductive and wasteful forms of land use. Viewed thus, land use should be treated not as the negation of property, but rather as a particular and constrained framing of the planning/property relationship. Put simply, land use asks certain questions of property, while eliding others. It becomes important, therefore, to open the “black box” of land use, in order to understand the important way in which planning practice engages private property.
Ambient pressure dependence of the subharmonic signal from ultrasound contrast microbubbles

Ultrasound contrast agents (UCA) microbubbles have been well recognized as a potential noninvasive tool for blood pressure measurement. The effect of ambient pressure on UCA subharmonic optimal driving frequency (SODF), at which the subharmonic scattering signals were maximal, was investigated experimentally. For groups of microbubbles with 80.1%±1.6% in the diameter range of 1μm-2μm, the shift of the SODF (SSODF) was 0.6MHz between overpressures of 4mmHg and 100mmHg, which was approximately twice of the corresponding shift of the resonance frequency. The SSODF may be as a novel and sensitive index of the local blood pressure estimation based on UCA microbubbles.
Intrafamilial transmission of hepatitis C virus: a systematic review

To examine the risk of hepatitis C virus (HCV) transmission between patients infected with HCV and their household members (siblings, offspring and parents), as well as their stable heterosexual partners, a systematic search of the MEDLINE database was undertaken for all relevant articles published up to June 1997. English language publications or those supplemented with an English abstract that reported studies concerning hepatitis C, and household, intrafamilial, sexual and intraspousal transmission of HCV, were reviewed. Data from uncontrolled and controlled studies were collected and analysed separately. Studies reporting the exclusive use of first‐generation anti‐HCV antibodies without supplemental tests were excluded. Pre‐ or postnatal mother‐to‐child transmission of HCV and homosexual and heterosexual transmission of HCV among non‐permanent couples were not included. Unweighted data from individual studies were pooled for each category of family member. Data were also analysed separately for Japanese and non‐Japanese studies because there is evidence that intrafamilial transmission may differ, based on endemicity of the viral infection. Comparisons were drawn only from controlled studies that reported the prevalence of HCV in family members of both HCV‐positive and HCV‐negative controls. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated for each family category. In uncontrolled studies, the pooled prevalence of anti‐HCV among 4250 stable sexual contacts of patients with HCV‐related chronic liver disease (CLD) was 13.48%, while the pooled prevalence of anti‐HCV among 580 stable sexual contacts of patients who contracted HCV as a result of multiple transfusions was 2.41%. In controlled studies, the pooled prevalence of anti‐HCV among 175 siblings and household contacts of patients with CLD was 4.0% compared with 0% among 109 contacts of anti‐HCV‐negative controls (OR 9.75, 95% CI 0.91 ad infinitum). The pooled prevalence of anti‐HCV among offspring of Japanese HCV‐infected CLD patients was 17% compared with 10.4% among offspring of HCV‐negative Japanese controls (OR 1.77, 95% CI 1.21–2.58, P=0.002). The pooled prevalence of anti‐HCV among spouses of non‐Japanese HCV‐infected CLD patients was 15.2% compared with 0.9% in the spouses of non‐Japanese HCV‐negative controls (OR 20.57, 95% CI 6.05–84.08, P=0.0001). The prevalence of anti‐HCV among non‐Japanese offspring and Japanese spouses of HCV‐infected patients was not increased compared with controls. HCV genotype homology and mutant analysis studies in pairs of HCV‐infected patients and their HCV‐infected contacts showed that concordant genotype homology was found in 66% of non‐sexual contacts and in 74% of sexual contacts. Sequence homology of greater than 92% was found in 19 out of 35 pairs. Hence, evidence exists that familial, non‐sexual and sexual transmission of HCV does occur. In Japanese patients, transmission probably occurs in younger family members while, in non‐Japanese patients, transmission probably occurs at an older age, after contact with an HCV‐infected spouse.
Electrocardiographic Transmural Dispersion of Repolarization in Patients with Inherited Short QT Syndrome

Background: Short QT syndrome (SQTS) carries an increased risk for sudden cardiac death. However, only a short QT interval does not express the risk of ventricular arrhythmias. Thus, additional evaluation of the repolarization abnormality in SQTS patients is essential. In experimental models of SQTS, increased transmural dispersion of repolarization (TDR) and its electrocardiographic counterpart T‐wave peak to T‐wave end interval (TPE) appeared critical for induction of polymorphic ventricular tachycardia (PMVT). In a clinical study with acquired long QT syndrome patients, TPE/QT ratio > 0.28 indicated arrhythmia risk. We hypothesized that the TPE/QT ratio would be greater in SQTS patients than in control subjects.
Electroencephalography (EEG)-Based Brain–Computer Interface (BCI): A 2-D Virtual Wheelchair Control Based on Event-Related Desynchronization/Synchronization and State Control

This study aims to propose an effective and practical paradigm for a brain-computer interface (BCI)-based 2-D virtual wheelchair control. The paradigm was based on the multi-class discrimination of spatiotemporally distinguishable phenomenon of event-related desynchronization/synchronization (ERD/ERS) in electroencephalogram signals associated with motor execution/imagery of right/left hand movement. Comparing with traditional method using ERD only, where bilateral ERDs appear during left/right hand mental tasks, the 2-D control exhibited high accuracy within a short time, as incorporating ERS into the paradigm hypothetically enhanced the spatiotemporal feature contrast of ERS versus ERD. We also expected users to experience ease of control by including a noncontrol state. In this study, the control command was sent discretely whereas the virtual wheelchair was moving continuously. We tested five healthy subjects in a single visit with two sessions, i.e., motor execution and motor imagery. Each session included a 20 min calibration and two sets of games that were less than 30 min. Average target hit rate was as high as 98.4% with motor imagery. Every subject achieved 100% hit rate in the second set of wheelchair control games. The average time to hit a target 10 m away was about 59 s, with 39 s for the best set. The superior control performance in subjects without intensive BCI training suggested a practical wheelchair control paradigm for BCI users.
TepiTool: A Pipeline for Computational Prediction of T Cell Epitope Candidates

Computational prediction of T cell epitope candidates is currently being used in several applications including vaccine discovery studies, development of diagnostics, and removal of unwanted immune responses against protein therapeutics. There have been continuous improvements in the performance of MHC binding prediction tools, but their general adoption by immunologists has been slow due to the lack of user‐friendly interfaces and guidelines. Current tools only provide minimal advice on what alleles to include, what lengths to consider, how to deal with homologous peptides, and what cutoffs should be considered relevant. This protocol provides step‐by‐step instructions with necessary recommendations for prediction of the best T cell epitope candidates with the newly developed online tool called TepiTool. TepiTool, which is part of the Immune Epitope Database (IEDB), provides some of the top MHC binding prediction algorithms for number of species including humans, chimpanzees, bovines, gorillas, macaques, mice, and pigs. The TepiTool is freely accessible at http://tools.iedb. org/tepitool/. © 2016 by John Wiley & Sons, Inc.
Differential levels of granzyme B, regulatory cytokines, and apoptosis in Crohn's disease and ulcerative colitis at first presentation

The mechanisms of tissue damage in ulcerative colitis and Crohn's disease may reflect disordered humoral or cell‐mediated effector mechanisms, respectively. Mucosal biopsies from untreated inflammatory bowel disease patients and normal controls were analysed for the expression of granzyme B, a cytotoxic effector molecule specifically associated with cell‐mediated immunity, and for regulatory cytokines. Messenger RNA (mRNA) was analysed by reverse transcription‐polymerase chain reaction and enzyme‐linked oligonucleotide chemiluminescence assay. Mucosal biopsies were analysed by immunohistochemistry for granzyme B protein and lymphocyte markers and for the presence of apoptotic cells by terminal deoxynucleotidyl transferase end labelling. Granzyme B mRNA was elevated in Crohn's disease, but not in ulcerative colitis or control mucosal biopsies. Granzyme B mRNA levels correlated with interferon gamma mRNA levels in Crohn's disease. Granzyme B was expressed in CD3+, CD8+ T cells in the lamina propria of Crohn's disease mucosa and there were significantly more apoptotic cells in the lamina propria in Crohn's disease. In conclusion, granzyme B‐expressing T lymphocytes are present in the focal mucosal lesions of Crohn's disease, together with spatially related apoptotic cell death. These results support the hypothesis that T‐cell‐mediated cytotoxic effector mechanisms may play a role in Crohn's disease. Copyright © 2000 John Wiley & Sons, Ltd.
Evaluation of whole brain health in aging and Alzheimer's disease: a standard procedure for scoring an MRI-based brain atrophy and lesion index.

BACKGROUND The Brain Atrophy and Lesion Index (BALI), a semi-quantitative rating scale, has been developed to evaluate whole brain structural changes in aging and Alzheimer's disease (AD). OBJECTIVE This study describes a standard procedure to score the BALI and train new raters for reliable BALI evaluation following this procedure. METHODS Structural MRI of subjects in the Alzheimer's Disease Neuroimaging Initiative dataset who had 3.0T, T1, and T2 weighted MRI scans at baseline and at 6, 12, and 24 month follow-ups were retrieved (n = 122, including 24 AD, 51 mild cognitive impairment patients, and 47 healthy control subjects). Images were evaluated by four raters following training with a step-by-step BALI process. Seven domains of structural brain changes were evaluated, and a total score was calculated as the sum of the sub-scores. RESULTS New raters achieved >90% accuracy after two weeks of training. Reliability was shown in both intra-rater correlation coefficients (ICC ≥ 0.92, p < 0.001) and inter-rater correlation coefficients (ICC ≥0.88, p < 0.001). Mean BALI total scores differed by diagnosis (F ≥ 2.69, p ≤ 0.049) and increased consistently over two years. CONCLUSION The BALI can be introduced using a standard procedure that allows new users to achieve highly reliable evaluation of structural brain changes. This can advance its potential as a robust method for assessing global brain health in aging, AD, and mild cognitive impairment.