Miracle-dz/UniFAR-FTUs huggingface dataset:
Amino Acid Sequence Requirements in the Hinge of Human Immunoglobulin A1 (IgA1) for Cleavage by Streptococcal IgA1 Proteases

ABSTRACT The amino acid sequence requirements in the hinge of human immunoglobulin A1 (IgA1) for cleavage by IgA1 proteases of different species of Streptococcus were investigated. Recombinant IgA1 antibodies were generated with point mutations at proline 227 and threonine 228, the residues lying on either side of the peptide bond at which all streptococcal IgA1 proteases cleave wild-type human IgA1. The amino acid substitutions produced no major effect upon the structure of the mutant IgA1 antibodies or their functional ability to bind to Fcα receptors. However, the substitutions had a substantial effect upon sensitivity to cleavage with some streptococcal IgA1 proteases, with, in some cases, a single point mutation rendering the antibody resistant to a particular IgA1 protease. This effect was least marked with the IgA1 protease from Streptococcus pneumoniae, which showed no absolute requirement for either proline or threonine at residues 227 to 228. By contrast, the IgA1 proteases of Streptococcus oralis, Streptococcus sanguis, and Streptococcus mitis had an absolute requirement for proline at 227 but not for threonine at 228, which could be replaced by valine. There was evidence in S. mitis that proteases from different strains may have different amino acid requirements for cleavage. Remarkably, some streptococcal proteases appeared able to cleave the hinge at a distant alternative site if substitution prevented efficient cleavage of the original site. Hence, this study has identified key residues required for the recognition of the IgA1 hinge as a substrate by streptococcal IgA1 proteases, and it marks a preliminary step towards development of specific enzyme inhibitors.
Regulation of intracellular sodium in cultured rat hippocampal neurones.

1. We studied regulation of intracellular Na+ concentration ([Na+]i) in cultured rat hippocampal neurones using fluorescence ratio imaging of the Na+ indicator dye SBFI (sodium‐binding benzofuran isophthalate). 2. In standard CO2/HCO3(‐)‐buffered saline with 3 mM K+, neurones had a baseline [Na+]i of 8.9 +/‐ 3.8 mM (mean +/‐ S.D.). Spontaneous, transient [Na+]i increases of 5 mM were observed in neurones on 27% of the coverslips studied. These [Na+]i increases were often synchronized among nearby neurones and were blocked reversibly by 1 microM tetrodotoxin (TTX) or by saline containing 10 mM Mg2+, suggesting that they were caused by periodic bursting activity of synaptically coupled cells. Opening of voltage‐gated Na+ channels by application of 50 microM veratridine caused a TTX‐sensitive [Na+]i increase of 25 mM. 3. Removing extracellular Na+ caused an exponential decline in [Na+]i to values close to zero within 10 min. Inhibition of Na+,K(+)‐ATPase by removal of extracellular K+ or ouabain application evoked a [Na+]i increase of 5 mM min‐1. Baseline [Na+]i was similar in the presence or absence of CO2/HCO3‐; switching from CO2/HCO3(‐)‐free to CO2/HCO3(‐)‐buffered saline, however, increased [Na+]i transiently by 3 mM, indicating activation of Na(+)‐dependent Cl(‐)‐HCO3‐ exchange. Inhibition of Na(+)‐K(+)‐2Cl‐ cotransport by bumetanide had no effect on [Na+]i. 4. Brief, small changes in extracellular K+ concentration ([K+]o) influenced neuronal [Na+]i only weakly. Virtually no change in [Na+]i was observed with elevation or reduction of [K+]o by 1 mM. Only 30% of cells reacted to 3 min [K+]o elevations of up to 5 mM. In contrast, long [K+]o alterations (> or = 10 min) to 6 mM or greater slowly changed steady‐state [Na+]i in the majority of cells. 5. Our results indicate several differences between [Na+]i regulation in cultured hippocampal neurones and astrocytes. Baseline [Na+]i is lower in neurones compared with astrocytes and is mainly determined by Na+,K(+)‐ATPase, whereas Na(+)‐dependent Cl(‐)‐HCO3‐ exchange, Na(+)‐HCO3‐ cotransport or Na(+)‐K(+)‐2Cl‐ cotransport do not play a significant role. In contrast to glial cells, [Na+]i of neurones changes only weakly with small alterations in bath [K+]o, suggesting that activity‐induced [K+]o changes in the brain might not significantly influence neuronal Na+,K(+)‐ATPase activity.
Economic and social changes in some Central and East European countries

In this article we used various indicators of the World Bank to be able to show and analyse some comparable data of economic and social changes for selected countries in Europe. We also used secondary data, such as published research of other authors, who had written about this subject to a narrower or broader extent. Some of the data are shown in graphics so that one can have better insight into economic (GNI and purchasing power parity per capita, distribution of income and consumption in some countries, export of goods and services) and social differences (infant mortality rate and survival to age 65) in the analysed countries. INTRODUCTION
TrkB gene transfer does not alter hippocampal neuronal loss and cognitive deficits following traumatic brain injury in mice.

PURPOSE The ability of brain-derived neurotrophic factor (BDNF) to attenuate secondary damage and influence behavioral outcome after experimental traumatic brain injury (TBI) remains controversial. Because TBI can result in decreased expression of the trkB receptor, thereby preventing BDNF from exerting potential neuroprotective effects, the contribution of both BDNF and its receptor trkB to hippocampal neuronal loss and cognitive dysfunction were evaluated. METHODS Full-length trkB was overexpressed in the left hippocampus of adult C57Bl/6 mice using recombinant adeno-associated virus serotype 2/5 (rAAV 2/5). EGFP (enhanced green fluorescent protein) expression was present at two weeks after AAV-EGFP injection and remained sustained up to four weeks after the injection. At 2 weeks following gene transduction, mice were subjected to parasagittal controlled cortical impact (CCI) brain injury, followed by either BDNF or PBS infusion into the hippocampus. RESULTS No differences were observed in learning ability at two weeks post-injury or in motor function from 48 hours to two weeks among treatment groups. The number of surviving pyramidal neurons in the CA2-CA3 region of the hippocampus was also not different among treatment groups. CONCLUSIONS These data suggest that neither overexpression of trkB, BNDF infusion or their combination affects neuronal survival or behavioral outcome following experimental TBI in mice.
Pivotal Role of TNF-α in the Development and Progression of Nonalcoholic Fatty Liver Disease in a Murine Model

Abstract Previously, we have shown that the adipocyte-specific nuclear form of sterol regulatory element-binding protein-1c (nSREBP-1c) transgenic mice spontaneously developed hepatic lesions that are similar to those of human nonalcoholic steatohepatitis (NASH) with a concomitant elevation of plasma TNF-α. In this study, we analyzed the role of TNF-α in the progression of nonalcoholic fatty liver disease (NAFLD). We established a Tnf knockout nSREBP-1c transgenic mouse line. Glucose tolerance and liver histology were examined at the age of 20 weeks. The gene expression and protein levels were assessed by quantitative RT-PCR and Western blot, respectively. The Tnf knockout improved glucose tolerance and significantly reduced the prevalence of hepatic steatosis (20% vs. 100%, p<0.0001) and fibrosis (15% vs. 65%, p=0.0057). The expressions of Acaca, Scd1, Mcp1, Tgfb1, Col1a1, and Timp1 were increased in the liver from the original nSREBP-1c transgenic mice. However, gene upregulation was reduced in the livers from the Tnf(−/−) nSREBP-1c transgenic mice. Furthermore, the hepatic levels of TIMP1 protein were increased in the original nSREBP-1c transgenic mice but not in Tnf(−/−) nSREBP-1c transgenic mice. To assess the direct effect of TNF-α on the expression of the genes, we cultured primary hepatocytes in the presence of TNF-α and found that TNF-α increased the expression of Mcp1, Tgfb1, and Timp1 in hepatocytes. These observations indicate that TNF-α plays a pivotal role in the development of NAFLD and progression to NASH through upregulating key molecules associated with lipid metabolism, inflammatory cytokines, and fibrosis in the liver.
A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia. AML Cooperative Study Group.

BACKGROUND Intensive chemotherapy for acute myelogenous leukemia (AML) continues to yield low rates of complete remission and survival among patients over the age of 65 years. Infection-related mortality is particularly high among these patients during the period of neutropenia that follows chemotherapy. We determined the effect of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) on mortality at eight weeks (the main end point) and the rate of complete remission among patients with AML who were 65 years old or older. METHODS After induction chemotherapy with daunorubicin (45 mg per square meter of body-surface area per day for 4 days) and cytarabine arabinoside (200 mg per square meter per day for 7 days), 173 patients with newly diagnosed AML were randomly assigned on day 8 to receive either lenograstim (5 micrograms per kilogram of body weight per day) or placebo, starting on day 9, until there was neutrophil recovery or a treatment failure, or for a maximum of 28 days. Salvage chemotherapy was also followed by lenograstim or placebo. Patients with a complete remission received two consolidation courses of chemotherapy without lenograstim or placebo. RESULTS The mortality rate at eight weeks was similar in the lenograstim and placebo groups (23 and 27 percent, respectively; P = 0.60), as was the incidence of severe infections. The median duration of neutropenia (absolute neutrophil count < or = 1000 per cubic millimeter) was shorter in the lenograstim group (21 days, as compared with 27 days in the placebo group; P < 0.001). Eight percent of the patients in both groups had regrowth of AML cells. The rate of complete remission was significantly higher in the lenograstim group (70 percent, as compared with 47 percent in the placebo group; P = 0.002). Overall survival, however, was similar in the two groups (P = 0.76). CONCLUSIONS The administration of lenograstim after chemotherapy for AML did not decrease the mortality rate at eight weeks among patients over the age of 65 years. The patients who received lenograstim had a significantly higher rate of complete remission than those who received placebo. Nevertheless, the overall survival in the two groups did not differ significantly.
Bone Marrow‐Derived Dendritic Cells Serve as Potent Adjuvants for Peptide‐Based Antitumor Vaccines

Dendritic cells (DCs) are considered the most effective antigen‐presenting cells (APCs) for primary immune responses. Since presentation of antigens to the immune system by appropriate professional APCs is critical to elicit a strong immune reaction and DCs seem to be quantitatively and functionally defective in the tumor host, DCs hold great promise to improve cancer vaccines. Even though they are found in lymphoid organs, skin and mucosa, the difficulty of generating large numbers of DCs has been a major limitation for their use in vaccine studies. A simple method for obtaining DCs from mouse bone marrow cells cultured in the presence of GM‐CSF + interleukin 4 is now available. In four different tumor models, mice injected with DCs grown in GM‐CSF plus interleukin 4 and prepulsed with a cytotoxic T lymphocyte‐recognized tumor peptide epitope developed a specific cytotoxic T lymphocyte response and were protected against a subsequent tumor challenge with tumor cells expressing the relevant tumor antigen. Moreover, treatment of day 5‐14 tumors with peptide‐pulsed DCs resulted in sustained tumor regression in five different tumor models. These results suggest that presentation of tumor antigens to the immune system by professional APCs is a promising method to circumvent tumor‐mediated immunosuppression and is the basis for ongoing clinical trials of cancer immunotherapy with tumor peptide‐pulsed DCs.
The pathophysiology of chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive pulmonary vascular disease that is usually a consequence of prior acute pulmonary embolism. CTEPH usually begins with persistent obstruction of large and/or middle-sized pulmonary arteries by organised thrombi. Failure of thrombi to resolve may be related to abnormal fibrinolysis or underlying haematological or autoimmune disorders. It is now known that small-vessel abnormalities also contribute to haemodynamic compromise, functional impairment and disease progression in CTEPH. Small-vessel disease can occur in obstructed areas, possibly triggered by unresolved thrombotic material, and downstream from occlusions, possibly because of excessive collateral blood supply from high-pressure bronchial and systemic arteries. The molecular processes underlying small-vessel disease are not completely understood and further research is needed in this area. The degree of small-vessel disease has a substantial impact on the severity of CTEPH and postsurgical outcomes. Interventional and medical treatment of CTEPH should aim to restore normal flow distribution within the pulmonary vasculature, unload the right ventricle and prevent or treat small-vessel disease. It requires early, reliable identification of patients with CTEPH and use of optimal treatment modalities in expert centres. CTEPH has complex pathophysiology including persistent organised thrombus and extensive small-vessel disease http://ow.ly/IgMH309hwmq
Ideonella sakaiensis sp. nov., isolated from a microbial consortium that degrades poly(ethylene terephthalate).

A Gram-stain-negative, aerobic, non-spore-forming, rod-shaped bacterium, designed strain 201-F6T, was isolated from a microbial consortium that degrades poly(ethylene terephthalate) (PET) collected in Sakai city, Japan, and was characterized on the basis of a polyphasic taxonomic study. The cells were motile with a polar flagellum. The strain contained cytochrome oxidase and catalase. It grew within the pH range 5.5-9.0 (optimally at pH 7-7.5) and at 15-42 ºC (optimally at 30-37 ºC). The major isoprenoid quinone was ubiquinone with eight isoprene units (Q-8). C16 : 0, C17 : 0 cyclo, C18 :1ω7c and C12 : 0 2-OH were the predominant cellular fatty acids. The major polar lipids were phosphatidylethanolamine, lyso-phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The G+C content of genomic DNA was 70.4 mol%. Phylogenetic analysis using the 16S rRNA gene sequences showed that strain 201-F6T was affiliated to the genus Ideonella, and was closely related to Ideonella dechloratans LMG 28178T (97.7 %) and Ideonella azotifigens JCM 15503T (96.6 %). Strain 201-F6T could be clearly distinguished from the related species of the genus Ideonella by its physiological and biochemical characteristics as well as by its phylogenetic position and DNA-DNA relatedness. Therefore, the strain represents a novel species of the genus Ideonella, for which the name Ideonella sakaiensis sp. nov. (type strain 201-F6T=NBRC 110686T=TISTR 2288T) is proposed.
Brain network analysis reveals affected connectome structure in bipolar I disorder

The notion that healthy brain function emerges from coordinated neural activity constrained by the brain's network of anatomical connections—i.e., the connectome—suggests that alterations in the connectome's wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in schizophrenia are indicative of altered connectome architecture including reduced communication efficiency, disruptions of central brain hubs, and affected “rich club” organization. Whether similar deficits are present in bipolar disorder is currently unknown. This study examines structural connectome topology in 216 bipolar I disorder patients as compared to 144 healthy controls, focusing in particular on central regions (i.e., brain hubs) and connections (i.e., rich club connections, interhemispheric connections) of the brain's network. We find that bipolar I disorder patients exhibit reduced global efficiency (−4.4%, P =0.002) and that this deficit relates (r = 0.56, P < 0.001) to reduced connectivity strength of interhemispheric connections (−13.0%, P = 0.001). Bipolar disorder patients were found not to show predominant alterations in the strength of brain hub connections in general, or of connections spanning brain hubs (i.e., “rich club” connections) in particular (all P > 0.1). These findings highlight a role for aberrant brain network architecture in bipolar I disorder with reduced global efficiency in association with disruptions in interhemispheric connectivity, while the central “rich club” system appears not to be particularly affected. Hum Brain Mapp 37:122–134, 2016. © 2015 Wiley Periodicals, Inc.
Diseases of Poverty with High Mortality in Infants and Children

Malaria, measles, lower respiratory infections, and diarrheal illnesses are common pediatric medical problems that are often fatal in the context of extreme poverty. In nonpoor environments, however, these infections are controlled and managed in ways that minimize mortality. From a scientific perspective, genetic variation among microbes is a frequent and important component of their epidemiology, pathophysiology, treatment, and prevention. From a public health perspective, relatively simple measures can reduce the mortal effects of these diseases until successful vaccines become available and immunizations programs are established. Infants and children are especially vulnerable to poor outcomes from infections when undernutrition and other circumstances of poverty are present.
Differences in health and taste attitudes and reported behaviour among Finnish, Dutch and British consumers: a cross-national validation of the Health and Taste Attitude Scales (HTAS)

The Health and Taste Attitude Scales (HTAS) developed by Roininen, Lähteenmäki and Tuorila in 1999 measure the importance of health and taste aspects of foods in the food choice process. These multi-item scales consist of sets of statements, ranging from "strongly disagree" to "strongly agree", which further divide into three Health (General health interest, Light product interest and Natural product interest) and three Taste (Craving for sweet foods, Using food as a reward and Pleasure) sub-scales. Finnish (N=467), Dutch (N=477), and British (N=361) respondents completed a questionnaire which contained four components: the HTAS, a separate "paper and pencil task" of choosing a food for a snack; pleasantness, healthiness and frequency of consumption of eight foods; and the Restraint Eating Scale of the Dutch Eating Behaviour Questionnaire (DEBQ). The latter three components were included in order to validate various aspects of the HTAS. The factor structure of HTAS was found to be equal in all three countries. However, there were some minor differences in factor loadings among countries, e.g. the Natural product interest and Pleasure sub-scale items had lower factor loadings in the UK than in Finland and The Netherlands. Finnish respondents had the most positive attitude towards light products. Dutch and British respondents scored higher on all Taste sub-scales than their Finnish counterparts. Respondents' health-related attitudes were good predictors of their "healthy food choices" in the snack task and self-reported consumption. Two of the Taste sub-scales (Craving for sweet foods and Using food as a reward) predicted well respondents' self-reported consumption of, for example, full-fat chocolate bars. All the Health and two of the Taste sub-scales proved to be useful tools for characterizing consumer attitudes within and between countries.
The prevalence of inflammatory and developmental odontogenic cysts in a Jordanian population: a clinicopathologic study.

OBJECTIVE To determine the prevalence of odontogenic jaw cysts in a Jordanian population and to compare these data with previously published reports from other geographic areas. METHOD AND MATERIALS The files on odontogenic jaw cysts treated between 1989 and 2001 in the Oral and Maxillofacial Pathology Diagnosis Service at the Department of Oral Medicine and Oral Surgery, Faculty of Dentistry, Jordan University of Science and Technology, were reviewed. Clinical and radiographic data were recorded and microscopic slides evaluated according to the most recent World Health Organization classification. Cases were analyzed with regard to age, sex, and anatomic site. RESULTS A diagnosis of odontogenic jaw cyst was established in 654 patients, with a male-to-female ratio of 1.7:1. Radicular cyst was the most common type of odontogenic cyst found (41.7%), followed by dentigerous cysts (24.8%). The peak age affected was between the third and fifth decades. Both jaws were almost equally affected. The most common anatomic site of incidence was the maxillary incisor/canine region, followed by the mandibular molar region. CONCLUSION This study indicates that there are some geographic differences with regard to the relative frequency, sex, and anatomic distributions of odontogenic cysts.
Agentisation of airports and the pursuit of regional development in Poland

The paper adopts the economic-geographical ideas of strategic coupling, path-dependence and path-creation to analyse the role of local/regional institutions in shaping the impacts of airports on regional development. By means of focusing on the airport industry (i.e. an integral component of the wider air transport system), the paper aims to help bridge the gap between economic geography, where air transport has received little attention, and transport geography, which so far has made little use of the theoretical advancements made in economic geography. The paper discusses the example of Poland where, further to the fall of communism, regional development became a key ambition for local and regional governments and where the importance of passenger aviation is rapidly increasing. Drawing from 16 interviews with airlines, Polish airports and Polish local authorities, and from documentary analysis, the paper explores the ways in which local/regional governments charge their airports with the path-shaping tasks of fostering strategic couplings with airlines and catalysing new forms of growth. This includes financial and political support, joint marketing and imposing challenging targets. The paper also shows that the transformation of Polish airports from passive assets into active agents of regional development (a process that is referred to as the ‘agentisation of airports’) is inherently path-dependent. The peculiar structure of ownership in the Polish airport industry (a partial legacy of the previous system) and the tensions between various actors that it spawns entangle Polish airports in the multi-scalar patterns of politics, which determine the effectiveness of their path-shaping roles.