Miracle-dz/UniFAR-FTUs huggingface dataset:
Bone Marrow Ly6Chigh Monocytes Are Selectively Recruited to Injured Kidney and Differentiate into Functionally Distinct Populations1

Roles for monocyte/macrophages (Mφ) in directing the development of tissue fibrosis are increasingly recognized. Macrophages form a heterogeneous group of inflammatory leukocytes, and the mechanisms by which they acquire heterogeneity and its functional significance are unclear. We used the unilateral ureteral obstruction model of progressive kidney fibrosis to explore macrophage heterogeneity and function further. Unilateral ureteral obstruction kidney Mφs form three distinct subpopulations defined by the marker Ly6C, all of which are derived from a single Ly6Chigh bone marrow monocyte population selectively recruited to the kidney. Conditional ablation of these Mφs in vivo in CD11b-DTR mice is potently antifibrotic. The mRNA transcription profile of these populations is consistent with differential functional roles for each subpopulation, with Ly6Clow macrophages transcribing genes consistent with selective profibrotic or M2-type function. Furthermore, bone marrow chimerism studies indicate that although resident kidney macrophages proliferate markedly to comprise up to 40% of the inflammatory macrophage population, they do not contribute to fibrosis. Our data identify Ly6C as a marker of functionally discrete tissue macrophage subsets and support a model of selective recruitment of Ly6Chigh bone marrow monocytes to the kidney that differentiate into three populations of kidney macrophages, including a profibrotic Ly6Clow population.
Acid hypersensitivity in patients with eosinophilic oesophagitis

Abstract Objective. Painful symptoms are prevalent in patients with eosinophilic oesophagitis but experimental data are sparse. The aim of this study was to compare the pain response to experimental oesophageal stimulation in 14 patients with eosinophilic oesophagitis and 15 healthy volunteers. Material and methods. A multimodal probe was placed in the oesophagus. The participants were subjected to mechanical, thermal and electrical pain stimuli followed by perfusion with 0.1 M HCl. Pain scores, referred pain areas and evoked brain potentials to electrical stimulation of the oesophagus were recorded. Results. Patients tolerated significantly less acid perfused in the oesophagus (median 123 versus 200 ml; P = 0.02) and felt the burning sensation evoked by the acid earlier (median 2.0 versus 5.0 min; P = 0.01). Eight patients had coexisting gastro-oesophageal reflux disease. Six patients had pure eosinophilic oesophagitis, and this group felt the acid earlier than those with concomitant reflux or the healthy volunteers (median 0.8 versus 2.0 and 5.0 min; P = 0.03). There were no differences between patients and controls in the responses to mechanical or thermal stimulation (P > 0.4). Furthermore, no differences were found for the proxies of central nervous system sensitization (response to electrical stimulations, referred pain areas or evoked brain potentials; P > 0.1). Conclusions. Patients with eosinophilic oesophagitis are hypersensitive to acid perfused in the oesophagus, and pathophysiologic findings are likely confined to the peripheral tissue. Reflux from physiological acid may play a role in the symptoms of eosinophilic oesophagitis.
Early Triggering of Exclusive IFN-γ Responses of Human Vγ9Vδ2 T Cells by TLR-Activated Myeloid and Plasmacytoid Dendritic Cells1

γδ T cells, a major innate-like T cell subset, are thought to play in vivo an important role in innate and adaptive immune responses to various infection agents like parasites, bacteria, or viruses but the mechanisms contributing to this immune process remain ill defined. Owing to their ability to recognize a broad set of microbial molecular patterns, TLRs represent a major innate pathway through which pathogens induce dendritic cells (DC) maturation and acquisition of immunostimulatory functions. In this study, we studied the effects of various TLR ligands on the activation of human Vγ9Vδ2 T cells, a main human γδ PBL subset, which has been recently involved in the licensing of mycobacteria-infected DC. Both TLR3 and TLR4, but not TLR2 ligands, induced a rapid, strong, and exclusive IFN-γ production by Vγ9Vδ2 T cells. This γδ subset contributed to a large extent to the overall PBL IFN-γ response induced after short-term TLR stimulation of human PBMC. Importantly, this phenomenon primarily depended on type I IFN, but not IL-12, produced by monocytic DC upon TLR engagement. Vγ9Vδ2 T cells were similarly activated by plasmacytoid DC upon TLR8/9 activation or Yellow Fever virus infection. Moreover TLR-induced Vγ9Vδ2 IFN-γ noncytolytic response led to efficient DC polarization into IL-12p70-producing cells. Our results support an adjuvant role played by Vγ9Vδ2 T cells along microbial infections through a particular cross-talk with pathogen-associated molecular patterns-activated DC. Moreover they provide new insights into the mechanisms underlying functional activation of this unique peripheral innate-like T cell subset during viral infections.
Negative Regulation of MAVS-Mediated Innate Immune Response by PSMA71

Innate immunity to viruses involves receptors such as Retinoic Acid Induced Gene-1 (RIG-I), which senses viral RNA and triggers a signaling pathway involving the outer mitochondrial membrane protein mitochondrial antiviral signaling (MAVS). Recent work has identified that NLRX1, a member of another class of innate immune receptors, sequesters MAVS away from RIG-I and thereby prevents mitochondrial antiviral immunity. In this study, we demonstrate that the proteasome PSMA7 (α4) subunit associates with MAVS in vivo and in vitro. Expression of PSMA7 results in a potent inhibition of RIG-1 and MAVS-mediated IFN-β promoter activity; conversely, depletion of PSMA7 with small interference RNA enhances virus-induced type I IFN production, with consequent reduction of virus replication. Furthermore, a striking reduction in the abundance of endogenous MAVS with overexpressed PSMA7 was found and virus infection leads to transient increase in the endogenous PSMA7 protein level. Cumulatively, these results suggest that PSMA7 is a negative regulator of the MAVS-mediated innate immunity that probably serves to attenuate the establishment of an antiviral state during viral infection, highlighting the biological significance of PSMA7-MAVS association as an important cellular regulatory control.
Divergent Roles of RelA and c-Rel in Establishing Chromosomal Loops upon Activation of the Igκ Gene1

Precise regulation of eukaryotic gene expression requires interactions between distal cis-acting regulatory sequences with the looping out of the intervening DNA, but how trans-acting regulatory proteins work to establish and maintain DNA loops during gene activation remains largely unexplored. LPS-induced transcription of the mouse Igκ gene in B lymphocytes utilizes three distal enhancers and requires the transcription factor NF-κB, whose family members include RelA and c-Rel. Using chromosome conformation capture technology in combination with chromatin immunoprecipitation, here we demonstrate that LPS-induced Igκ gene activation creates chromosomal loops by bridging together all three pairwise interactions between the distal enhancers and RNA polymerase II, the apparent molecular tie for the bases of these loops. RelA and actin polymerization are essential for triggering these processes, which do not require new transcription, protein synthesis, or c-Rel. We have thus identified both essential and nonessential events that establish higher order chromatin reorganization during Igκ gene activation.
Removal of asymmetric dimethylarginine during artificial liver support using fractionated plasma separation and adsorption

Abstract Objective. Asymmetric dimethylarginine (ADMA) is the most potent endogenous nitric oxide synthase inhibitor. Elevated ADMA levels have been linked to increased mortality in different patient populations. Key regulation of ADMA levels mainly takes place in the liver. Hence, ADMA is elevated in liver disease. There is no specific pharmacological treatment to lower the elevated ADMA levels. Hemodialysis is of limited efficiency in removing ADMA as it is highly protein bound. Prometheus® is an extracorporeal liver support system which allows the removal of protein-bound toxins. We assessed the efficiency of the Prometheus® system in reducing high ADMA levels in patients with liver failure. Material and methods. We studied nine patients with acute-on-chronic liver failure and concomitant renal failure already necessitating hemodialysis. Seven patients needed intensive care treatment. Two consecutive sessions of Prometheus® therapy of each 4 h were performed in all patients. ADMA and its structural isomer symmetrical dimethylarginine (SDMA) were determined using liquid chromatography–mass spectrometry. Results. ADMA levels correlated to model for end stage liver disease (MELD) score (rs = 0.62; p < 0.0001). Before Prometheus® was started, levels of ADMA and SDMA were elevated (1.36 ± 0.5 μmol/l and 1.90 ± 0.4 μmol/l, respectively). During Prometheus® treatments, plasma levels of ADMA dropped by a mean 25% (p < 0.0001) and SDMA levels by 22% (p < 0.0001). However, there was a significant rebound of ADMA levels between the two therapy sessions (p < 0.01). Conclusions. This study shows for the first time that plasma levels of ADMA can be effectively lowered by an artificial liver support system (Prometheus®). Effective elimination of ADMA might explain some of the beneficial clinical effects of these systems in patients with liver failure.
Mapping industrial systems - a supply network perspective on enabling technologies, processes and actors

This paper develops a multi-layered multi-stage mapping approach to explore the characteristics of emerging industry supply networks (EI SNs), and how enabling production technologies and supply chain processes are supported by institutional, industrial and supply network actors. The mapping methodology involves the systematic capture of material transformations, enabling product and process technologies, and the actors, both institutional and industrial that might facilitate industrial development. A key research challenge was to extend traditional methods of SN mapping and value chain analysis that typically adopt a narrow focal firm perspective of a firm's supply network, to also include key institutional, and other industrial system actors that form part of the wider industrial ecosystem. An industrial ecosystem mapping methodology was therefore developed that integrates and extends value chain analysis with SN configuration mapping, applied to a broader industrial systems context. The methodology is demonstrated in selected EI sectors to demonstrate the utility of the approach.
Cellular sources of MMP-7, MMP-13 and MMP-28 in ulcerative colitis

Abstract Objective. Matrix metalloproteinases (MMPs) are considered the predominant proteases in the pathogenesis of mucosal ulcerations associated with inflammatory bowel disease (IBD). Whether the malignancy associated MMP-7 and MMP-13 or the recently cloned MMP-28 convey a certain meaning for intestinal homeostasis and pathogenesis of IBD is currently unknown. We therefore set off to analyze regulation patterns and cellular origins of these MMPs in mucosal tissues of patients with ulcerative colitis (UC). Material and methods. Biopsy samples of affected and healthy tissues were obtained from 35 Norwegian patients with UC. RNA was quantified by quantitative real-time polymerase chain reaction to study MMP gene expression in both pathological and healthy mucosal specimens. Cellular origins were determined by immunohistology using surrogate markers for inflammation, neovascularization, and epithelial structures. Protein expression of MMP-7 and MMP-13 was quantified using enzyme-linked immunosorbent assay. Results. MMP-7 and MMP-13 gene expression was significantly increased in UC affected colonic mucosa whereas MMP-28 showed a decreased expression in inflamed mucosa. Endothelial cells and infiltrating leukocytes were identified as the major cellular sources of MMP-7 and MMP-13 in UC. Enterocytes represented the major cellular source of MMP-28 in healthy and inflamed mucosa. Conclusions. MMP-7 and MMP-13 expression in inflammatory and endothelial cells indicate a role of these MMPs for both colitis associated neoangiogenesis and inflammatory changes. Decreased MMP-28 expression in UC is most likely the result of colitis associated epithelial destruction and loss of cryptal architecture.
A longitudinal study of tooth growth in a single individual based on long‐ and short‐period incremental markings in dentine and enamel

Ground sections of teeth from a single individual revealed approximately 30 fluorescent lines in the dentine resulting from successive courses of tetracycline antibiotics given over a period of approximately 12 years. In addition, many teeth showed long‐period incremental markings in the dentine. Short‐period daily cross‐striations in the enamel were used to calculate the periodicity of the long‐period incremental lines in both enamel and dentine. The incremental markings in the dentine were then used to calibrate the time of administration of each of the courses of tetracycline antibiotics. Enlarged micrographs of the teeth, constructed using fluorescence microscopy, were used to measure the increase in height of different teeth throughout the growth period on each occasion the tetracycline antibiotics were given. The times of initial mineralization of the teeth and the duration of crown formation were also determined for each tooth section. Line plots of tooth height against age were computed and used to calculate the rate of increase in tooth height during crown and root formation for one example of each tooth type. Initial rates of increase in height during enamel apposition and coronal dentine formation were fast, between 10 μm and 14 μm per day. During the latter phase of crown formation and during early root formation, tooth height increased at a slower rate of between 4 μm and 6 μm per day. Rates of increase in tooth height then rose to between 13 μm and 26 μm per day during the second half of root formation before falling off to a rate of approximately 4 μm per day during root completion (as the root apex formed). The times of initial crown mineralization and the total crown formation times estimated in this individual were all within the range known for modern humans but there was comparatively early mineralization of the third permanent molar. These findings are discussed in the context of other studies on human dental development. Copyright © 1993 John Wiley & Sons, Ltd
Refining a meta-methodology for collaborative networked organisations: a case study

Presently, there is a great need for methodologies and reference models to assist and guide the creation and operation of various types of enterprises, including Collaborative Networked Organisations (CNO). The efforts to fulfil this need can be significantly assisted by a meta-methodology integrating current and future CNO creation and operation knowledge. This paper presents a milestone in an iterative and reflective action research aiming to demonstrate the feasibility of such a meta-methodology. The study describes a field experiment combined with a case study and subsequent reflections leading to the refinement and extension of the proposed meta-methodology.
The development, distribution and maintenance of trust in distributed work groups: a social network approach

An increasing number of teams and groups have members who are distributed at multiple sites, often working in different departments or organisations, sometimes also in different countries. Although separated in space, such units must collaborate and deliver results and value to their organisations. It is now generally acknowledged that trust is a core asset for such groups, as it can help to reduce conflicts and enhance knowledge sharing and efficiency. This article argues that a network approach can be useful for developing a deeper understanding of trust in such groups. The network approach is particularly useful in providing an understanding of the development, distribution and maintenance of trust across organisational, geographical and cultural boundaries. These aspects are described and illustrated in a case study of a distributed work group in an international telecommunications company.
Oral Health Knowledge, Attitude and Practices Amongst Teachers of Public School Set-up of Karach, Pakistan

Background: Schools provide an effective forum to enhance general as well as oral health awareness amongchildren and the teachers may serve as pioneer role models to motivate children towards healthy lifestyle. Thecurrent study reflects at one of the components of a school-based oral health education initiative, projected bya public dental institute of Karachi, Pakistan. The objective was to assess the knowledge, attitude and practicesrelate dental health amongst teachers of public schools of Karachi, Pakistan.Methodology: It was a 6-month cross-sectional study. Two-stage cluster sampling was utilized; in first stage,a list of public schools located in Saddar town was acquired and ten schools were randomly selected. In secondstage, 12 teachers were selected at random from the list of teachers acquired from each selected school. Hence,total 120 teachers were requested to participate in questionnaire-based study.Results: Sixty-two percent teachers lacked knowledge about tooth decay. Seventy-four percent identified sugaras an etiological factor for caries while 44% identified bacteria as the primary cause of tooth decay. Sixty-sixpercent teachers were aware about the protective role of fluoride against dental caries and 48% did not feel thatbrushing teeth of babies with a tooth-paste was a necessity. Sixty-five percent rated their oral health as goodand 67% had visited a dentist. All teachers brushed regularly but only 9% used favorable amount of toothpaste.Conclusion: Teachers had poor knowledge regarding dental diseases and etiology of tooth decay however; theywere informed about benefits of fluoride as well as importance of dental visits
Gastric phenotype in children with Helicobacter pylori infection undergoing upper endoscopy

Abstract Introduction. Helicobacter pylori is a definite risk factor for the development of gastric cancer, especially in the context of corpus-predominant gastritis. The infection is usually acquired in early childhood, implying lifelong exposure to this carcinogen if untreated. Our objective was to analyze the prevalence of H. pylori induced corpus-predominant gastritis in children. Material and methods. We analyzed the results of 265 esophagogastroduodenoscopies (EGD) in children performed between February 2006 and August 2008; 34 endoscopies were excluded (24 with follow-up investigations, 5 with incomplete data, 5 adults). H. pylori gastritis was defined by the presence of H. pylori in histology or by a positive rapid urease test. Grade of inflammation was rated according to the updated Sydney Scoring System. Gastritis was classified as corpus-predominant when the degree of chronic inflammation was higher in the corpus than in the antrum and vice versa for antrum-predominant gastritis. Results. Two hundred thirty-one patients (128 female; mean age ± SEM: 10.5 ± 3.5 years) were analyzed. Eighty-four (36%) were H. pylori positive, 147 (64%) patients were negative for H. pylori. In H. pylori positive patients, 39 (46%) patients had pangastritis (one patient with mucosal atrophy, which is regarded as precancerous lesion), 42 (50%) had antrum-predominant gastritis and 3 (4%) had corpus-predominant gastritis. One female patient (15.6 years old) with severe (grade 3) pangastritis had focal mucosal atrophy in both antrum and corpus, but no patient had intestinal metaplasia. Conclusions. Corpus-predominant gastritis develops in H. pylori infected children, while mucosal atrophy and intestinal metaplasia develop later in the course of the infection.
Zinc in muliple sclerosis

Zinc profiles were examined in 68 patients with multiple sclerosis, 62 normal volunteers, and 13 patients with other neurological diseases. Plasma zinc levels were slightly increased in patients with multiple sclerosis and significantly increased in those with other neurological impairments (p <0.01), compared with control subjects. Albumin‐bound as well as protein‐bound zinc levels were normal in all groups tested. The α2 macroglobulin‐bound zinc level was significantly lower (p < 0.01) in patients with multiple sclerosis than in control subjects. Erythrocyte‐bound zinc levels were significantly increased (p < 0.05) in patients with multiple sclerosis when compared with control subjects. Erythrocyte‐bound zinc was normal in patients with other neurological impairments. Because erythrocyte‐bound zinc levels are relatively independent of daily fluctuations in dietary zinc intake, an increase in these values may suggest alterations in the control mechanisms governing zinc compartmentalization in patients with multiple sclerosis.
Anti-elongation factor-1α autoantibody in adult atopic dermatitis patients

Adult atopic dermatitis (AD) patients develop severe facial lesions, which sometimes distribute in sun-exposed areas similar to the rash of systemic lupus erythematosus. To declare autoimmunity in the pathogenesis of AD, we investigated serum antinuclear antibody (ANA) in 256 adult AD patients and identified its ligands. A high titer of ANA was found in 31.3% of AD patients and 75% of the ANA showed a homogenous pattern. Sixty-five percent of ANA F sera reacted to a 52 kDa protein (p52) in HeLa cell immunoblots. By screening the HeLa cell cDNA expression library with anti-p52 sera, a clearly positive clone was isolated. The sequence of this cDNA was identical to human elongation factor (hEF)-1a. The eluate of IgG bound to hEF-1a‐glutathione S-transferase (GST) fusion protein recognized a band at 52 kDa in a HeLa cell immunoblot, and stained Hep-2 cell nuclei and cytoplasma as reported in hEF-1a distribution. The anti-p52 AD sera recognized the hEF-1a‐GST fusion protein. The anti-hEF-1a antibody-positive AD patients were characterized by higher facial involvement and lower white blood cell counts compared with antibody-negative patients. The present results suggest the possible involvement of autoimmunity in the pathogenesis of adult AD.
Major Differences in the Responses of Primary Human Leukocyte Subsets to IFN-β

Treatment of cell lines with type I IFNs activates the formation of IFN-stimulated gene factor 3 (STAT1/STAT2/IFN regulatory factor-9), which induces the expression of many genes. To study this response in primary cells, we treated fresh human blood with IFN-β and used flow cytometry to analyze phosphorylated STAT1, STAT3, and STAT5 in CD4+ and CD8+ T cells, B cells, and monocytes. The activation of STAT1 was remarkably different among these leukocyte subsets. In contrast to monocytes and CD4+ and CD8+ T cells, few B cells activated STAT1 in response to IFN-β, a finding that could not be explained by decreased levels of IFNAR2 or STAT1 or enhanced levels of suppressor of cytokine signaling 1 or relevant protein tyrosine phosphatases in B cells. Microarray and real-time PCR analyses revealed the induction of STAT1-dependent proapoptotic mRNAs in monocytes but not in B cells. These data show that IFN-stimulated gene factor 3 or STAT1 homodimers are not the main activators of gene expression in primary B cells of healthy humans. Notably, in B cells and, especially in CD4+ T cells, IFN-β activated STAT5 in addition to STAT3, with biological effects often opposite from those driven by activated STAT1. These data help to explain why IFN-β increases the survival of primary human B cells and CD4+ T cells but enhances the apoptosis of monocytes, as well as to understand how leukocyte subsets are differentially affected by endogenous type I IFNs during viral or bacterial infections and by type I IFN treatment of patients with multiple sclerosis, hepatitis, or cancer.