Miracle-dz/UniFAR-FTUs huggingface dataset:
Structural dynamics of oligodendrocyte lysis by perforin in culture: Relevance to multiple sclerosis

The mechanism by which oligodendrocytes are depleted from active lesions in multiple sclerosis (MS) is not clear but many reports implicate a cytolytic process. The most applied animal model for MS, chronic relapsing experimental autoimmune encephalomyelitis (EAE), has been established in inbred strains of mice, especially SJL and PL. Studies on oligodendrocytes from these strains in vitro have been hampered to date by an inability to grow these cells from mouse CNS tissue. We report here a successful method to culture SJL mouse oligodendrocytes and have analyzed lysis of these cells in vitro mediated by the pore‐forming protein, perforin, a candidate effector molecule in inflammatory demyelination. Cultures were exposed to murine perforin, 36–72 hemolytic U, for up to 2.5 hr and examined using the oligodendrocyte phenotypic markers O4, galactocerebroside and myelin basic protein (MBP), in addition to a membrane dye (DiI) and a marker of necrosis, propidium iodide, (PI). Cultures were imaged chronologically by phase contrast, immunofluorescence, digital, light and electron microscopy. Findings showed that the majority of oligodendrocytes were killed within 60–90 min via pore expansion and ultimately, membrane disruption. The structural features of the cellular damage comprised swelling of the cell body, fenestration and fragmentation of membranes and processes, cytoplasmic vacuolation and breakdown of the nuclear envelope. Astrocytes in the same system were relatively resistant to cell lysis. The above patterns of oligodendrocyte damage in SJL oligodendrocytes were reminiscent of patterns in the MS lesion, leaving us to conclude that perforin may play an important role in the human disease. J. Neurosci. Res. 64:380–391, 2001. © 2001 Wiley‐Liss, Inc.
Heterogeneity in 5-HT-Induced Contractile and Proliferative Responses in Rat Pulmonary Arterial Bed

Aims: 5-Hydroxytryptamine (5-HT) is a potent vasoconstrictor and mitogen in the pulmonary vascular bed which exhibits phenotypical and functional heterogeneity according to size of the vessels. Methods: We thus investigated both contractile response and smooth muscle cell (SMC) proliferation in response to 5-HT in rat main extrapulmonary artery (MPA) and intrapulmonary arteries of the first and second order (IPA1 and IPA2). Results: The contractile effect of 5-HT was higher in IPA1 and IPA2 compared to MPA. 5-HT2 receptor antagonists like ketanserin and ritanserin and a 5-HT1B/D receptor antagonist, GR127935, partially inhibited the contraction. α-Methyl-5-HT, a 5-HT2 receptor agonist, induced a higher contraction in MPA than in IPA and inversely 5-carboxamidotryptamine, a 5-HT1 receptor agonist, induced a higher contraction in IPA2 than in MPA and IPA1. Nitrendipine reduced the contraction, whereas the addition of thapsigargin, an inhibitor of the sarcoplasmic reticulum Ca-ATPases, had an additive blocking effect only in IPA1. The residual contraction to 5-HT was abolished by Y-27632, a rho kinase inhibitor. Finally, SMC proliferation in response to 5-HT was higher in MPA than in IPA2. Conclusion: Our results demonstrate regional differences in SMC proliferation as well as in the functional role of 5-HT receptors and the sarcoplasmic reticulum in the contraction.
Midbrain-hindbrain boundary patterning and morphogenesis are regulated by diverse grainy head-like 2-dependent pathways

The isthmic organiser located at the midbrain-hindbrain boundary (MHB) is the crucial developmental signalling centre responsible for patterning mesencephalic and metencephalic regions of the vertebrate brain. Formation and maintenance of the MHB is characterised by a hierarchical program of gene expression initiated by fibroblast growth factor 8 (Fgf8), coupled with cellular morphogenesis, culminating in the formation of the tectal-isthmo-cerebellar structures. Here, we show in zebrafish that one orthologue of the transcription factor grainy head-like 2 (Grhl2), zebrafish grhl2b plays a central role in both MHB maintenance and folding by regulating two distinct, non-linear pathways. Loss of grhl2b expression induces neural apoptosis and extinction of MHB markers, which are rescued by re-expression of engrailed 2a (eng2a), an evolutionarily conserved target of the Grhl family. Co-injection of sub-phenotypic doses of grhl2b and eng2a morpholinos reproduces the apoptosis and MHB marker loss, but fails to substantially disrupt formation of the isthmic constriction. By contrast, a novel direct grhl2b target, spec1, identified by phylogenetic analysis and confirmed by ChIP, functionally cooperates with grhl2b to induce MHB morphogenesis, but plays no role in apoptosis or maintenance of MHB markers. Collectively, these data show that MHB maintenance and morphogenesis are dissociable events regulated by grhl2b through diverse transcriptional targets.
Crohn's disease, pregnancy, and birth weight

OBJECTIVE:Although there is general agreement that conception should be avoided when Crohn's disease is active, many questions remain unanswered for the woman with Crohn's disease in remission who becomes pregnant.METHODS:Sixty-five charts of women with Crohn's disease quiescent at the start of pregnancy were identified between January 1993 and December 1997. Each pregnancy was matched to a healthy control pregnancy by date, age, parity, smoking status, and gestational age ± 1 wk, and comparisons were carried out using matched analyses.RESULTS:The two groups were similar in terms of maternal height, weight, and body mass index (BMI), in addition to the matched variables. The incidence of pregnancy complications was similar for most of the complications examined, whereas the incidence of poor maternal weight gain differed significantly between the groups (17/65 vs 2/65, p < 0.001). Flare-up of the Crohn's disease was seen in 13/65 (20%) of pregnancies. The greatest differences in neonatal outcomes were in terms of birth weight (3150 ± 80 g vs 3500 ± 60 g) and birth weight percentile (36.7%± 3.6% vs 57.5%± 3.4%). Overall, there were 16 (24.6%) small for gestational age (SGA) births in the Crohn's group, compared with only one (1.5%) in the control group (p = 0.0007). Multivariate analysis was performed to identify factors predictive of SGA births in the Crohn's group. Ileal Crohn's disease was a statistically significant predictor (p = 0.035), whereas previous bowel resection trended toward statistical significance (p = 0.065). CONCLUSIONS:In view of the risk of low birth weight, all women with Crohn's disease who become pregnant should be followed carefully during the pregnancy, particularly those who have ileal disease or who have previously undergone bowel resection. Furthermore, smoking cessation needs to be aggressively pursued in these patients.
Leptospira interrogans Induces Apoptosis in Macrophages via Caspase-8- and Caspase-3-Dependent Pathways

ABSTRACT Apoptosis of host cells plays an important role in modulating the pathogenesis of many infectious diseases. It has been reported that Leptospira interrogans, the causal agent of leptospirosis, induces apoptosis in macrophages and hepatocytes. However, the molecular mechanisms responsible for host cell death remained largely unknown. Here we demonstrate that L. interrogans induced apoptosis in a macrophage-like cell line, J774A.1, and primary murine macrophages in a time- and dose-dependent manner. Apoptosis was associated with the activation of cysteine aspartic acid-specific proteases (caspase-3, caspase-6, and caspase-8), the increased expression of Fas-associated death domain (FADD), and the cleavage of the caspase substrates poly(ADP-ribose) polymerase (PARP) and nuclear lamina protein (lamin A and lamin C). Caspase-9 was activated to a lesser extent, whereas no release of cytochrome c from mitochondria was detectable. Inhibition of caspase-8 impaired L. interrogans-induced caspase-3 and -6 activation, as well as PARP and lamin A/C cleavage and apoptosis, suggesting that apoptosis is initiated via caspase-8 activation. Furthermore, caspase-3 was required for the activation of caspase-6 and seemed to be involved in caspase-9 activation through a feedback amplification loop. These data indicate that L. interrogans-induced apoptosis in macrophages is mediated by caspase-3 and -6 activation through a FADD-caspase-8-dependent pathway, independently of mitochondrial cytochrome c-caspase-9-dependent signaling.
Ribosome profiling reveals pervasive and regulated stop codon readthrough in Drosophila melanogaster

Ribosomes can read through stop codons in a regulated manner, elongating rather than terminating the nascent peptide. Stop codon readthrough is essential to diverse viruses, and phylogenetically predicted to occur in a few hundred genes in Drosophila melanogaster, but the importance of regulated readthrough in eukaryotes remains largely unexplored. Here, we present a ribosome profiling assay (deep sequencing of ribosome-protected mRNA fragments) for Drosophila melanogaster, and provide the first genome-wide experimental analysis of readthrough. Readthrough is far more pervasive than expected: the vast majority of readthrough events evolved within D. melanogaster and were not predicted phylogenetically. The resulting C-terminal protein extensions show evidence of selection, contain functional subcellular localization signals, and their readthrough is regulated, arguing for their importance. We further demonstrate that readthrough occurs in yeast and humans. Readthrough thus provides general mechanisms both to regulate gene expression and function, and to add plasticity to the proteome during evolution. DOI: http://dx.doi. org/10.7554/eLife.01179. 001
Independently Evolved Virulence Effectors Converge onto Hubs in a Plant Immune System Network

An analysis of protein-protein interactions in Arabidopsis identifies the plant interactome. Plants generate effective responses to infection by recognizing both conserved and variable pathogen-encoded molecules. Pathogens deploy virulence effector proteins into host cells, where they interact physically with host proteins to modulate defense. We generated an interaction network of plant-pathogen effectors from two pathogens spanning the eukaryote-eubacteria divergence, three classes of Arabidopsis immune system proteins, and ~8000 other Arabidopsis proteins. We noted convergence of effectors onto highly interconnected host proteins and indirect, rather than direct, connections between effectors and plant immune receptors. We demonstrated plant immune system functions for 15 of 17 tested host proteins that interact with effectors from both pathogens. Thus, pathogens from different kingdoms deploy independently evolved virulence proteins that interact with a limited set of highly connected cellular hubs to facilitate their diverse life-cycle strategies.
Aliskiren reduces body‐weight gain, adiposity and plasma leptin during diet‐induced obesity

Background and purpose: Overfeeding increases adipose tissue mass and leptin production and up‐regulates the renin‐angiotensin system in adipose tissue in rodents. Here, we determined the effect of chronic treatment with the renin inhibitor, aliskiren, in a model of diet‐induced obesity in mice, on: (i) body weight, adipose tissue weight and plasma leptin; (ii) food intake and caloric efficiency; and (iii) angiotensin II (Ang II) in adipose tissue.
Inactivation of parvovirus B19 by liquid heating incorporated in the manufacturing process of human intravenous immunoglobulin preparations

Several reports have suggested the possible transmission of human parvovirus B19 (B19) through the administration of plasma derivatives that had undergone virus inactivation by various types of heat treatment. However, none of the reports evaluated and discussed the inactivation of B19 by the heat treatment that is implemented in the individual manufacturing processes of such products. The present study evaluated the ability to inactivate B19 of liquid‐heat treatment at 60°C for 10 h that was incorporated in the manufacturing process of intravenous human immunoglobulin preparations. The results showed that B19 was rapidly inactivated under the conditions used for the liquid‐heat treatment.
The effect of recurrent miscarriage and infertility on the risk of pre‐eclampsia

Objective Pre‐eclampsia, recurrent miscarriage and infertility may all partly be caused by unsuccessful placentation early in pregnancy. If so, one will expect these disorders to be associated in population studies. The aim of the present investigation was to estimate the risk of pre‐eclampsia in women with recurrent miscarriage and infertility.
Belief Revision, Conditional Logic and Nonmonotonic Reasoning

We consider the connections between belief revision, conditional logic and nonmonotonic reasoning, using as a foundation the approach to theory change developed by Alchourron, Gardenfors and Makinson (the AGM approach). This is first generalized to allow the iteration of theory change operations to capture the dynamics of epistemic states according to a principle of minimal change of entrenchment. The iterative operations of expansion, contraction and revision are characterized both by a set of postulates and by Grove’s construction based on total pre-orders on the set of complete theories of the belief logic. We present a sound and complete conditional logic whose semantics is based on our iterative revision operation, but which avoids Gardenfors’s triviality result because of a severely restricted language of beliefs and hence the weakened scope of our extended postulates. In the second part of the paper, we develop a computational approach to theory dynamics using Rott’s E-bases as a representation for epistemic states. Under this approach, a ranked E-base is interpreted as standing for the most conservative entrenchment compatible with the base, reflecting a kind of foundationalism in the acceptance of evidence for a belief. Algorithms for the computation of our iterative versions of expansion, contraction and revision are presented. Finally, we consider the relationship between nonmonotonic reasoning and both conditional logic and belief revision. Adapting the approach of Delgrande, we show that the unique extension of a default theory expressed in our conditional logic of belief revision corresponds to the most conservative belief state which respects the theory: however, this correspondence is limited to propositional default theories. Considering first order default theories, we present a belief revision algorithm which incorporates the assumption of independence of default instances and propose the use of a base logic for default reasoning which incorporates uniqueness of names. We conclude with an examination of the behavior of an implemented system on some of Lifschitz’s benchmark problems in nonmonotonic reasoning.
Incremental Validity of Person-Organization Fit Over the Big Five Personality Measures

ABSTRACT Few studies have provided the validity evidence of a measure of objective person-organization fit (P-O fit) as a selection tool. The present study used a concurrent validation design to examine the criterion-related validity and the incremental validity of a P-O fit measure beyond the validity of the Big Five personality test for predicting job performance (task performance and organizational citizenship behavior) and employee commitment (organizational commitment and supervisory commitment) for a group of high-tech professional employees in Taiwan. Results showed that P-O fit predicted the contextual component of overall job performance and was significantly related to two types of employee commitment. Moreover, P-O fit had an incremental validity beyond that of the personality measures for predicting some of our outcome variables.
Effects of Concurrent Noise and Jet Fuel Exposure on Hearing Loss

We sought to examine the effects of occupational exposure to jet fuel on hearing in military workers. Methods: Noise-exposed subjects, with or without jet fuel exposure, underwent hearing tests. Work histories, recreational exposures, protective equipment, medical histories, alcohol, smoking, and demographics were collected by questionnaire. Jet fuel, solvent, and noise exposure data were collected from records. Fuel exposure estimates were less than 34% of the OSHA Threshold Limit Values. Results: Subjects with 3 years of jet fuel exposure had a 70% increase in adjusted odds of hearing loss (OR = 1.7; 95% CI = 1.14–2.53) and the odds increased to 2.41 (95% CI = 1.04–5.57) for 12 years of noise and fuel exposure. Conclusions: These findings suggest that jet fuel has a toxic affect on the auditory system.
An efficient primary-segmented backup scheme for dependable real-time communication in multihop networks

Several distributed real-time applications (e.g., medical imaging, air traffic control, and video conferencing) demand hard guarantees on the message delivery latency and the recovery delay from component failures. As these demands cannot be met in traditional datagram services, special schemes have been proposed to provide timely recovery for real-time communications in multihop networks. These schemes reserve additional network resources (spare resources) a priori along a backup channel that is disjoint with the primary. Upon a failure in the primary channel, its backup is activated, making the real-time connection dependable. In this paper, we propose a new method of providing backups called segmented backups, in which backup paths are provided for partial segments of the primary path rather than for its entire length, as is done in the existing schemes. We show that our method offers: 1) improved network resource utilization; 2) higher average call acceptance rate; 3) better quality-of-service guarantees on propagation delays and failure-recovery times; and 4) increased flexibility to control the level of fault tolerance of each connection separately. We provide an algorithm for routing the segmented backups and prove its optimality with respect to spare resource reservation. We detail necessary extensions to resource reservation protocol (RSVP) to support our scheme and argue that they increase the implementation complexity of RSVP minimally. Our simulation studies on various network topologies demonstrate that spare resource aggregation methods such as backup multiplexing are more effective when applied to our scheme than to earlier schemes.
Reinforcement Learning of Traffic Light Controllers Adapting to Traffic Congestion

Due to the increasing amounts of traffic in and around urban areas there is a growing need for intelligent traffic lights that optimize traffic flow. In this paper we describe the optimization of traffic light controllers using a multi-agent, model-based reinforcement learning or approximate real-time dynamic programming approach. Our methods optimize individual traffic lights locally, but the optimization takes into account traffic congestion at neighboring traffic lights, such that there is implicit cooperation between them. We show, using experiments performed with a traffic simulator, that this approach outperforms existing methods.
Increase in the Population of Duodenal Immunoglobulin A Plasmocytes in Axenic Mice Associated with Different Living or Dead Bacterial Strains of Intestinal Origin

Various bacterial strains were tested for their ability to stimulate immunoglobulin A (IgA) plasmocytes to populate the duodenal lamina propria in axenic mice. The mice were associated with the strains for at least 4 weeks. The strains inhabiting the conventional mouse intestine and belonging to the genera Lactobacillus, Streptococcus, Eubacterium, Actinobacillus, Micrococcus, Corynebacterium, and Clostridium (including the extremely oxygen-sensitive ones) are only slightly or nonimmunogenic, whereas the strains belonging to the genera Bacteroides and Escherichia have an immunogenic effect. The same result was obtained with Bacteroides and Escherichia strains isolated from the digestive tract of other animal species. The kinetics of appearance of intestinal IgA plasmocytes are similar in axenic mice monoassociated with a stimulatory strain and in conventional mice. The association of two or more strains with axenic mice leads either to the same or a greater number of duodenal IgA plasmocytes as that obtained with the most stimulatory strain monoassociated with axenic mice. The maximum stimulation recorded in all of these trials represents about two-thirds of that observed in conventional mice and was obtained in the duodenum of gnotoxenic mice harboring four bacterial strains isolated from the conventional mouse microflora. The orally administered killed cells of two immunogenic strains, E. coli and Bacteroides sp. , are as immunogenic as the living cells, provided that their concentration in the digestive tract is sufficient.
An investigation of indoor air quality assessment in office buildings

Over the last several years studies have shown that the quality of indoor air may be worse than outdoor air. People spend as much as 90% of their time indoors, therefor, the associated health risk due to indoor air pollution may be greater than the risk due to outdoor air pollution. Building designs have altered dramatically over the last two decades resulted in "tighter" buildings that rely on sophisticated mechanical systems to provide for the quantity of air required throughout the building. These changes over the years could result in an increased number of complaints received regarding Sick Building Syndrome symptoms. The World Health Organization (WHO) estimates that up to 30% of office buildings world-wide may have significant problems regarding poor indoor air quality (IAQ). This study involves a literature study of the major indoor air pollutants regarding the source of the pollutant, the associated health effects, the measuring techniques available and the results of previous studies conducted on the specific pollutant. Measurements will be taken in two sealed buildings, one an old and the other a new building to identify the major pollutants. A questionnaire was compiled specifically for building occupants and completed by the occupants of both buildings. From the results obtained a step-by-step method for solving indoor air quality (IAQ) problems was proposed. The method was applied and evaluated in a case study of a problem building where indoor air quality related problems were experienced. The results of the study revealed that the major indoor air pollutants are present in old as well
Willingness to Pay for Recreational Benefit Evaluation in a Wastewater Reuse Project. Analysis of a Case Study

The study deals with the evaluation of the recreational benefit of a reclaimed water reuse project in the municipality of Ferrara, north Italy, by means of the contingent valuation method. It also provides an analysis of the public acceptance of the project, determined by eliciting the willingness of the local people to contribute to the realization of this project in monetary terms (their willingness to pay). The project involves the upgrade of the existing wastewater treatment plant by conventional (rapid sand filters) and natural (constructed wetland) treatments. The latter will be constructed within the urban park surrounding the wastewater treatment plant area and will combine the objectives of both wastewater treatment with recreational services, since they will create equipped green areas open to the public. The study is based on the answers provided by 400 respondents, who are residents in the four districts of the municipality of Ferrara. It emerges that willingness to pay is strongly influenced by the socio-economic characteristics of the respondents, with an amount on average of 48 €/family.