Miracle-dz/UniFAR-FTUs huggingface dataset:
Hemokinin-1 Activates the MAPK Pathway and Enhances B Cell Proliferation and Antibody Production

Hemokinin 1 (HK-1) is a substance P-like tachykinin peptide predominantly expressed in non-neuronal tissues. In addition to a prominent function in lymphoid development, recent studies indicate a potential role for HK-1 in immunoregulation. The current study was focused on its action on mature B cells. Despite the negligible effect on its own, HK-1 exhibited a profound influence on B cell activation elicited by several classical signals, including LPS stimulation, BCR cross-linking, and CD40 ligation. Cells therefore showed enhanced proliferation, survival, and CD80/86 expression, and produced more IgM with a higher frequency of Ab-forming cells. Biochemical analysis revealed that HK-1 alone was sufficient to induce the activation of MAPKs and the expression of Blimp-1 and Xbp-1 in B cells. Nevertheless, costimulation with a known B cell activator resulted in much enhanced phosphorylation of MAPKs and transcriptional activation of Blimp-1 and Xbp-1. Overall, these data support that HK-1 provides an important costimulatory signal for B cell activation, possibly through synergistic activation of the MAPK pathway and induction of transcription factors critical for plasmacytic differentiation.
Fear Not: Neurobiological Mechanisms of Fear and Anxiety

Fear is a common, core emotion. Moreover, anxiety disorders are among the most common form of psychiatric disease. In this thesis neuroimaging, genetic, pharmacological, brain stimulation and behavioral techniques were used in healthy subjects and specific patient populations to shed more light on the neuroanatomical and pharmacological systems that underlie human fear and anxiety. Our results provide new insights into the limbic upregulation and prefrontal downregulation of defensive states. We delineated neuroanatomical systems that may play an important role in fear regulation in response to the on- and offset of acute stressors. We extended work that implicated common genetic variation in serotonin transporter function as a possible prelude to anxiety by showing that serotonin transporter genotype is associated with basic defensive reactivity as indexed by fear-potentiated startle and functional magnetic resonance imaging measures of anxiety. We made first steps in the development of paradigms that may aid in the discovery of new and improved medication for anxiety disorders. Finally, we performed fear-potentiated startle measurements in two very rare populations: subjects with a rare genetic defect leading to selective calcification of the lateral amygdala and subjects that received deep brain stimulation at the ventral striatum to treat severe obsessive-compulsive symptoms. The latter two studies enabled us to obtain unique information on the contribution of these brain regions to fear learning and basic defensive reactions.
Perspectives on industrial clusters in the Japanese biotechnology industry

Recent developments in Japanese biotechnology clusters are examined. The biotechnology industry in Japan is rapidly evolving from its primary stage. As a result of the efforts of national and regional government, the number of bio-ventures is increasing in many regions. Through the industrial cluster plans and regional projects, it is becoming possible to comprehend the clusters, which are being formed in various parts of Japan. Value-added roles of intermediaries in clusters are described as follows: building trust among firms or participants through council, providing workforce development and training programs, facilitating access to shared resources.
Alpha-2 agonists and analgesia

In addition to their anti-hypertensive effects, alpha-2 agonists also cause analgesia. Since analgesia from these drugs is due primarily to actions in the spinal cord, it is not surprising that analgesia is poor after systemic administration, but profound after injection near the cord (spinal or epidural administration). Advantages of alpha-2 agonists over opioids in the treatment of severe pain include lack of opioid type side effects (addiction, nausea, respiratory depression, pruritus), lack of abuse potential and efficacy in special situations where opioids fail (opioid tolerance, neuropathic pain, reflex sympathetic dystrophy). Clonidine, the lead compound in this category, has been administered epidurally or spinally to over 1,000 patients in published reports, and detailed cerebrospinal fluid pharmacokinetics and pharmacodynamics have been described. Epidural clonidine has been designated as an orphan product in the US for the treatment of intractable cancer pain, and a multi-centre, placebo-contro.
TLR9-Dependent Induction of Intestinal α-Defensins by Toxoplasma gondii

α-Defensins (or Cryptdins [Crps]) are a group of antimicrobial peptides produced as a component of Paneth cell (PC) secretory granules in the small intestine. In vivo ligation of TLR9 by synthetic agonists leads to PC degranulation, although the mechanism by which this occurs remains uncertain. In this report, we investigated TLR9-dependent mechanisms, triggered by the parasite Toxoplasma gondii, inducing Crp release in the lumen. Oral challenge of C57BL/6J (B6) wild-type (WT) mice with T. gondii induced TLR9 mRNA upregulation associated with a marked increase of type I IFN mRNA expression. PC secretory granules were released, and Crp-3/-5 mRNA expression by purified epithelial cells was increased following oral challenge of B6 WT mice. Although PCs failed to degranulate in infected B6 TLR9−/− mice, i.p. injection of mouse IFN-β alone led to Crp-3/-5 mRNA upregulation in B6 WT and TLR9−/− mice. In addition, modulation of Crp mRNA expression in response to T. gondii infection was abrogated in B6 IFNAR−/− mice, which lack a functional type I IFN receptor. Taken together, these data demonstrate that T. gondii induces Crp-3/-5 production and release by PCs via a TLR9-dependent production of type I IFNs. Crps have a limited direct effect against T. gondii but may indirectly affect the early control of T. gondii invasiveness by promoting the initiation of a protective Th1 response against the parasite.
Antibodies to the Desmoglein 1 Precursor Proprotein but Not to the Mature Cell Surface Protein Cloned from Individuals without Pemphigus1

In pemphigus foliaceus (PF), autoantibodies against desmoglein 1 (Dsg1) cause blisters. Using Ab phage display, we have cloned mAbs from a PF patient. These mAbs, like those from a previous patient, were directed against mature Dsg1 (matDsg1) on the cell surface of keratinocytes and precursor Dsg1 (preDsg1) in the cytoplasm. To determine whether individuals without pemphigus have B cell tolerance to Dsg1, we cloned mAbs from two patients with thrombotic thrombocytopenic purpura and a healthy person. We found mAbs against preDsg1, but not matDsg1. All but 1 of the 23 anti-preDsg1 mAbs from PF patients and those without PF used the VH3-09 (or closely related VH3-20) H chain gene, whereas no PF anti-matDsg1 used these genes. VH cDNA encoding anti-preDsg1 had significantly fewer somatic mutations than did anti-matDsg1 cDNA, consistent with chronic Ag-driven hypermutation of the latter compared with the former. These data indicate that individuals without PF do not have B cell tolerance to preDsg1 and that loss of tolerance to matDsg1 is not due to epitope shifting of anti-preDsg1 B cells (because of different VH gene usage). However, presentation of peptides from Dsg1 by preDsg1-specific B cells may be one step in developing autoimmunity in PF.
Preoperative prognostic factors for mortality in peptic ulcer perforation: a systematic review

Abstract Objective. Mortality and morbidity following perforated peptic ulcer (PPU) is substantial and probably related to the development of sepsis. During the last three decades a large number of preoperative prognostic factors in patients with PPU have been examined. The aim of this systematic review was to summarize available evidence on these prognostic factors. Material and methods. MEDLINE (January 1966 to June 2009), EMBASE (January 1980 to June 2009), and the Cochrane Library (Issue 3, 2009) were screened for studies reporting preoperative prognostic factors for mortality in patients with PPU. The methodological quality of the included studies was assessed. Summary relative risks with 95% confidence intervals for the identified prognostic factors were calculated and presented as Forest plots. Results. Fifty prognostic studies with 37 prognostic factors comprising a total of 29,782 patients were included in the review. The overall methodological quality was acceptable, yet only two-thirds of the studies provided confounder adjusted estimates. The studies provided strong evidence for an association of older age, comorbidity, and use of NSAIDs or steroids with mortality. Shock upon admission, preoperative metabolic acidosis, tachycardia, acute renal failure, low serum albumin level, high American Society of Anaesthesiologists score, and preoperative delay >24 h were associated with poor prognosis. Conclusions. In patients with PPU, a number of negative prognostic factors can be identified prior to surgery, and many of these seem to be related to presence of the sepsis syndrome.
The Anti-Inflammatory and Proresolving Mediator Resolvin E1 Protects Mice from Bacterial Pneumonia and Acute Lung Injury

Whereas pneumonia is the most common cause of death and disability worldwide, most cases of pneumonia spontaneously resolve. Mechanisms that promote pneumonia resolution remain to be determined. Resolvin E1 (RvE1) is an endogenous mediator that displays proresolving actions in sterile inflammation. In this study, we developed a new model of aspiration pneumonia to evaluate the effect of RvE1 on acute lung injury caused by acid aspiration and subsequent bacterial challenge. Mice received hydrochloric acid into the left lung followed by the enteric pathogen Escherichia coli. I.v. administration of RvE1 (∼0.005 mg/kg) prior to acid injury selectively decreased lung neutrophil accumulation by 55% and enhanced clearance of E. coli. RvE1 significantly decreased lung tissue levels of several proinflammatory chemokines and cytokines, including IL-1β, IL-6, HMGB-1, MIP-1α, MIP-1β, keratinocyte-derived chemokine, and MCP-1, in a manner independent of the anti-inflammatory mediators IL-10 and lipoxin A4. In addition, animals treated with RvE1 had a marked improvement in survival. These findings in experimental aspiration pneumonia have uncovered protective roles for RvE1 in pathogen-mediated inflammation that are both anti-inflammatory for neutrophils and protective for host defense, suggesting that RvE1 represents the first candidate for a novel therapeutic strategy for acute lung injury and pneumonia that harnesses natural resolution mechanisms.
Actualización acerca de Borrelia burgdorferi sensu lato y enfermedad de Lyme

Introduccion: Borrelia burgdorferi sensu lato es el agente etiologico de la enfermedad de Lyme, zoonosis emergente de dificil diagnostico, prevencion y control, reportada fundamentalmente en el hemisferio norte. Objetivo: facilitar informacion actualizada acerca de Borrelia burgdorferi. Metodos: se realizo una revision de la literatura cientifica y especializada sobre los principales aspectos relacionados con este agente y su enfermedad; como son las caracteristicas de las borrelias y el ciclo de vida, epidemiologia, manifestaciones clinicas en humanos, diagnostico de laboratorio, definicion actual de caso, tratamiento, profilaxis, prevencion y control. Resultados: se expone informacion actualizada y valiosa sobre los temas seleccionados, util para el personal interesado en las enfermedades infecciosas transmitidas por vectores. Se muestra ademas informacion sobre los estudios realizados en Cuba. Conclusiones: se aporta informacion de utilidad para el manejo epidemiologico, clinico y microbiologico de casos con sospechas de la infeccion por Borrelia burgdorferi sensu lato Introduction: Borrelia burgdorferi sensu lato is the causative agent of Lyme disease, an emerging zoonosis, whose diagnosis, prevention and control are difficult and it is mainly reported in the northern hemisphere. Objective: to provide updated information about Borrelia burgdorferi. Methods: a review of scientific and specialized literature on the key aspects of this agent and the disease such as characteristics and life cycle of borrelias, epidemiology, clinical manifestations in humans, laboratory diagnosis, current case definition, treatment, prophylaxis, prevention and control. Results: current valuable information on selected items was set forth, which is useful for the personnel involved in vector-borne infectious diseases. Additionally, information about studies conducted in Cuba was provided. Conclusions: this paper offers updated information for the epidemiological, clinical and microbiological management of suspected cases of infection with Borrelia burgdorferi sensu lato
Differential Role of the Fas/Fas Ligand Apoptotic Pathway in Inflammation and Lung Fibrosis Associated with Reovirus 1/L-Induced Bronchiolitis Obliterans Organizing Pneumonia and Acute Respiratory Distress Syndrome1

Bronchiolitis obliterans organizing pneumonia (BOOP) and acute respiratory distress syndrome (ARDS) are two clinically and histologically distinct syndromes sharing the presence of an inflammatory and fibrotic component. Apoptosis via the Fas/Fas ligand (FasL) pathway plays an important role in the development of acute lung injury and fibrosis characteristic of these and other pulmonary inflammatory and fibrotic syndromes. We evaluated the role of apoptosis via the Fas/FasL pathway in the development of pulmonary inflammation and fibrosis in reovirus 1/L-induced BOOP and ARDS. CBA/J mice were intranasally inoculated with saline, 1 × 106 (BOOP), or 1 × 107 (ARDS) PFU reovirus 1/L, and evaluated at various days postinoculation for in situ apoptosis by TUNEL analysis and Fas/FasL expression. Our results demonstrate the presence of apoptotic cells and up-regulation of Fas/FasL expression in alveolar epithelium and in infiltrating cells during the inflammatory and fibrotic stages of both reovirus 1/L-induced ARDS and BOOP. Treatment of mice with the caspase 8 inhibitor, zIETD-fmk, inhibited apoptosis, inflammation, and fibrotic lesion development in reovirus 1/L-induced BOOP and ARDS. However, CBA/KlJms-Faslpr-cg/J mice, which carry a point mutation in the Fas cytoplasmic region that abolishes the ability of Fas to transduce an apoptotic signal, do not develop pulmonary inflammation and fibrotic lesions associated with reovirus 1/L-induced BOOP, but still develop inflammation and fibrotic lesions associated with reovirus 1/L-induced ARDS. These results suggest a differential role for the Fas/FasL apoptotic pathway in the development of inflammation and fibrotic lesions associated with BOOP and ARDS.
Information Technology and Quantitative Management ( ITQM 2013 ) An EMM-based Approach for Text Classification

In this paper, a classification method named explicit Markov model is applied for text classification. Currently some machine learning technologies, such as support vector machine (SVM), have been discussed widely in text classification. However, these methods consider that any two features are independent and ignore the language structure information. Hidden Markov model is a powerful tool for sequence tagging problems. This paper presents a new method called explicit Markov model (EMM) which is based on HMM for text classification. EMM make better use of the context information between the observation symbols. Our experiments are conducted on three datasets: Reuter s 21578 R8 dataset, WebKB and Fudan University Chinese text classification corpus. Experimental results show that the performance of EMM is comparable to SVM for text classification. © 2013 The Authors. Published by Elsevier B.V. Selection and/or peer-review under responsibility of the organizers of the 2013 International Conference on Computational Science
Independent Regulation of Chemokine Responsiveness and Cytolytic Function versus CD8+ T Cell Expansion by Dendritic Cells

The ability of cancer vaccines to induce tumor-specific CD8+ T cells in the circulation of cancer patients has been shown to poorly correlate with their clinical effectiveness. In this study, we report that although Ags presented by different types of mature dendritic cells (DCs) are similarly effective in inducing CD8+ T cell expansion, the acquisition of CTL function and peripheral-type chemokine receptors, CCR5 and CXCR3, requires Ag presentation by a select type of DCs. Both “standard” DCs (matured in the presence of PGE2) and type 1-polarized DCs (DC1s) (matured in the presence of IFNs and TLR ligands, which prevent DCs “exhaustion”) are similarly effective in inducing CD8+ T cell expansion and acquisition of CD45RO+IL-7R+IL-15R+ phenotype. However, granzyme B expression, acquisition of CTL activity, and peripheral tissue-type chemokine responsiveness are features exclusively exhibited by CD8+ T cells activated by DC1s. This advantage of DC1s was observed in polyclonally activated naive and memory CD8+ T cells and in blood-isolated melanoma-specific CTL precursors. Our data help to explain the dissociation between the ability of cancer vaccines to induce high numbers of tumor-specific CD8+ T cells in the blood of cancer patients and their ability to promote clinical responses, providing for new strategies of cancer immunotherapy.
Reduced 13C-d-xylose absorption in alcoholics is more likely caused by alterations in small intestinal mucosa than delayed gastric emptying

Abstract Objective. Alterations of the small intestinal absorptive surface are a probable cause of d-xylose malabsorption in chronic alcoholism. Delayed gastric emptying, however, may influence the 13C-d-xylose breath test, which is used to study intestinal function in alcoholics. The aim of this study was to measure gastric emptying in alcoholics to elucidate whether retention of the test meal could explain the malabsorptive pattern of the 13C-d-xylose breath test observed in alcoholics. Material and methods. Fifteen alcoholics performed the 13C-octanoic acid and the 13C-d-xylose breath tests on consecutive days in a random order. The 13CO2 expired was measured every 30 or 15 min for 4 h in the 13C-d-xylose and the 13C-octanoic acid breath tests, respectively, using a mass spectrometer equipped with a gas chromatograph. Test meals consisted of 100 mg of 13C-d-xylose and 5 g of unmarked d-xylose dissolved in 250 ml water and 91 mg 13C-octanoic acid embedded in a one-egg omelette served with white bread with margarine, respectively. Results. The alcoholic patients had a lower 13C-d-xylose breath index compared with healthy controls (p < 0.0001). None of the 13C-octanoic acid breath test variables, T50%, Tmax, Tlag, or GEC revealed any significant differences between the groups. Conclusion. The pathological 13C-d-xylose breath test in this group of alcoholics is unlikely to be caused by delayed gastric emptying. Malabsorption is the probable cause of the pathological 13C-d-xylose breath test results in alcoholics.
Cerebrovascular Diseases and Associated Risk Factors in WHO Eastern Mediterranean Countries

Background: In the WHO Eastern Mediterranean region, nearly onemillion deaths are caused by cardio-vascular diseases every year. During the last decade, the number of deaths caused by stroke increased by 23%. Most cardiovascular diseases can be prevented by addressing behavioural risk factors such as tobacco use, alco hol, unhealthy diet, physical inactivity, and metabolic risk factors like obesity, high blood pressure, diabetes and raised lipids. Methods: This is a systematic review on cerebrovascular diseases and associated risk factors in WHO Eastern Mediterranean countries. Medline, Science Direct, and other sources were used to get peer reviewed papers dealing with the review theme. The search was limited to publications between 1990 and 2013 (30th June). Results and Discussion: According to the inclusion criteria, 45 papers were included in the present review. The prevalence was found greater than 50% in 38 studies for hypertension, greater than 25% in 36 studies for diabetes, greater than 15% in 26 studies for smoking and greater than 25% in 19 studies for dyslipi
Colonic mucosal lesions associated with low-dose aspirin: A case control study

Abstract Objective. Low-dose aspirin (LDA) is widely used because it reduces the risk of vascular events in patients with atherosclerosis. Recently, there has been a substantial increase in prescriptions for LDA. We analyzed the risk of colonic mucosal lesions associated with the long-term use of LDA. Material and methods. Among Japanese patients who underwent a colonoscopy between January 2004 and December 2006, 199 colitis cases and 5764 non-colitis controls were identified after excluding 749 patients based on study criteria. The history of LDA use was compared between the cases and controls and the multivariate (age-, sex- and underlying diseases-) adjusted odds ratio (OR) was estimated using a multiple logistic regression model. Results. The adjusted OR for colonic mucosal lesions associated with LDA use versus non-use was 1.45 [95% confidence interval (CI), 0.87–2.42; p = 0.152]. In terms of gender differences, the OR for LDA-induced colitis in females was significantly increased at 2.55 (95% CI, 1.31–4.94; p = 0.006) but was not significantly increased in males at 0.70 (95% CI, 0.34–1.45; p = 0.334). Conclusions. In females, LDA increased the risk of colonic mucosal lesions, suggesting that LDA may contribute to the pathogenesis of colonic ulceration or colitis. Therefore, it is essential that prescribing physicians be aware of the risk of LDA-induced colonic lesions.
Lactic Acid and Acidification Inhibit TNF Secretion and Glycolysis of Human Monocytes

High concentrations of lactic acid (LA) are found under various pathophysiological conditions and are accompanied by an acidification of the environment. To study the impact of LA on TNF secretion, human LPS-stimulated monocytes were cultured with or without LA or the corresponding pH control. TNF secretion was significantly suppressed by low concentrations of LA (≤10 mM), whereas only strong acidification had a similar effect. This result was confirmed in a coculture model of human monocytes with multicellular tumor spheroids. Blocking synthesis of tumor-derived lactate by oxamic acid, an inhibitor of lactate dehydrogenase, reversed the suppression of TNF secretion in this coculture model. We then investigated possible mechanisms underlying the suppression. Uptake of [3-13C]lactate by monocytes was shown by hyphenated mass spectrometry. As lactate might interfere with glycolysis, the glycolytic flux of monocytes was determined. We added [1,2-13C2]glucose to the culture medium and measured glucose uptake and conversion into [2,3-13C2]lactate. Activation of monocytes increased the glycolytic flux and the secretion of lactate, whereas oxygen consumption was decreased. Addition of unlabeled LA resulted in a highly significant decrease in [2,3-13C2]lactate secretion, whereas a mere corresponding decrease in pH exerted a less pronounced effect. Both treatments increased intracellular [2,3-13C2]lactate levels. Blocking of glycolysis by 2-deoxyglucose strongly inhibited TNF secretion, whereas suppression of oxidative phosphorylation by rotenone had little effect. These results support the hypothesis that TNF secretion by human monocytes depends on glycolysis and suggest that LA and acidification may be involved in the suppression of TNF secretion in the tumor environment.