Miracle-dz/UniFAR-FTUs huggingface dataset:
Increased Production of Interleukin-8 in Primary Human Monocytes and in Human Epithelial and Endothelial Cell Lines after Dengue Virus Challenge

ABSTRACT The more severe form of dengue virus infection, dengue hemorrhagic fever, is characterized by plasma leakage and derangements in hemostasis. As elevated interleukin-8 (IL-8) levels have been observed in sera from patients with more severe disease manifestations, a study was initiated to look at the effect of dengue virus infection in vitro on proinflammatory cytokine secretion and expression. A significant increase in IL-8 levels in the culture supernatant of primary human monocytes infected with dengue 2 virus (D2V) New Guinea C (NGC) was found by enzyme-linked immunosorbent assay. Additionally, by reverse transcriptase PCR, the mRNA was also augmented. Among the proinflammatory cytokines and their mRNAs measured (IL-6, IL-1β, IL-8, and tumor necrosis factor alpha), IL-8 showed the greatest change following D2V infection. Similarly, two cell lines, 293T (a human epithelial cell line) and ECV304 (an endothelial cell line), were permissive to D2V NGC and responded to the infection by increasing the synthesis of IL-8. Nuclear factor kappa B (NF-κB) and nuclear factor IL-6 (NFIL-6) are primary mediators of IL-8 expression. We studied the transcriptional regulation of IL-8 in the ECV304 and 293T cell lines and found that the induction of IL-8 gene expression involved the activation of NF-κB (P = 0.001) and, to a lesser extent, the activation of NFIL-6 in ECV304 cells only. We next observed by the chromatin immunoprecipitation procedure in vivo acetylation of core histones bound to the IL-8 promoter after D2V infection. IL-8 produced by infected monocytes and also IL-8 that may be produced by endothelial or other epithelial cells is associated with the hyperacetylation of histones bound to the IL-8 promoter in addition to the activation of transcription by NF-κB. We hypothesize that the overall increase in IL-8 synthesis observed in this in vitro study may play a role in the pathogenesis of the plasma leakage seen in dengue hemorrhagic fever and dengue shock syndrome.
Characterization of a Nuclear Export Signal within the Human T Cell Leukemia Virus Type I Transactivator Protein Tax*

Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. The HTLV-I transactivator protein Tax plays an integral role in the etiology of adult T cell leukemia, as expression of Tax in T lymphocytes has been shown to result in immortalization. In addition, Tax is known to interface with numerous transcription factor families, including activating transcription factor/cAMP response element-binding protein and nuclear factor-κB, requiring Tax to localize to both the nucleus and cytoplasm. In this report, the nucleocytoplasmic localization of Tax was examined in Jurkat, HeLa, and U-87 MG cells. The results reported herein indicate that Tax contains a leucine-rich nuclear export signal (NES) that, when fused to green fluorescent protein (GFP), can direct nuclear export via the CRM-1 pathway, as determined by leptomycin B inhibition of nuclear export. However, cytoplasmic localization of full-length Tax was not altered by treatment with leptomycin B, suggesting that native Tax utilizes another nuclear export pathway. Additional support for the presence of a functional NES has also been shown because the NES mutant Tax(L200A)-GFP localized to the nuclear membrane in the majority of U-87 MG cells. Evidence has also been provided suggesting that the Tax NES likely exists as a conditionally masked signal because the truncation mutant TaxΔ214-GFP localized constitutively to the cytoplasm. These results suggest that Tax localization may be directed by specific changes in Tax conformation or by specific interactions with cellular proteins leading to changes in the availability of the Tax NES and nuclear localization signal.
Developing a model for supply chain agility and innovativeness to enhance firms’ competitive advantage

Purpose Developing agility and innovativeness as dynamic capabilities are important for firms to sustain their competitive advantage in today’s global economy. The purpose of this paper is to develop and empirically test a framework to investigate how the supply chain agility and innovativeness are achieved through IT integration and trust in members of supply chain and how these, in turn, can enhance firms’ competitive advantage. Design/methodology/approach This research employs a survey method and data are collected from senior managers working in the supply chain or IT area. The model and hypotheses are tested utilizing data from 204 usable Taiwan manufacturing firms via structural equations modeling methodology. Findings The study demonstrates that both IT integration and trust in supply chain members significantly enhance supply chain agility and innovativeness, which in turn positively affect firm’s competitive advantage. The results indicate that IT integration and trust are antecedents and major joint partnership resources for improving supply chain agility and innovativeness. Research limitations/implications Data are collected from manufacturing industry in Taiwan and single respondent from each firm, the generalizability of current findings to other industries or countries should require additional investigation. Practical implications The study suggests that a firm should focus on IT integration and trust in supply chain members to achieve supply chain agility and innovativeness. To take advantage of supply chain agility and innovativeness, through maximizing firm’s competitive advantage, firms should continually adapt to the fast changing business environment and search for creative ways to satisfy new market needs. Originality/value Given the attention paid to supply chain agility and innovativeness in terms of importance to responding to business uncertainty and competitiveness, and more recently, as important capabilities in managing supply chain management, this paper investigates how IT integration and trust can contribute to supply chain agility and innovativeness. Provide evidence regarding the impact of IT integration and trust on agility of supply chains, innovativeness and competitive advantage.
THE COEVOLUTION OF PARASITES WITH HOST‐ACQUIRED IMMUNITY AND THE EVOLUTION OF SEX

Abstract. Here I present a deterministic model of the coevolution of parasites with the acquired immunity of their hosts, a system in which coevolutionary oscillations can be maintained. These dynamics can confer an advantage to sexual reproduction within the parasite population, but the effect is not strong enough to outweigh the twofold cost of sex. The advantage arises primarily because sexual reproduction impedes the response to fluctuating epistasis and not because it facilitates the response to directional selection—in fact, sexual reproduction often slows the response to directional selection. Where the cost of sexual reproduction is small, a polymorphism can be maintained between the sexuals and the asexuals. A polymorphism is maintained in which the advantage gained due to recombination is balanced by the cost of sex. At much higher costs of sex, a polymorphism between the asexual and sexual populations can still be maintained if the asexuals do not have a full complement of genotypes available to them, because the asexuals only outcompete those sexuals with which they share the same selected alleles. However, over time we might expect the asexuals to amass the full array of genotypes, thus permanently eliminating sexuals from the population. The sexuals may avoid this fate if the parasite population is finite. Although the model presented here describes the coevolution of parasites with the acquired immune responses of their hosts, it can be compared with other host‐parasite models that have more traditionally been used to investigate Red Queen theories of the evolution of sex.
Nonsensory target-dependent organization of piriform cortex

Significance The mammalian olfactory system is capable of detecting and discriminating a vast and diverse array of small organic molecules or odorants. Complex blends of these chemicals are finally perceived as a unified odor object—for example, a rose contains dozens of active compounds. The piriform cortex (PCX) is the largest component of the olfactory cortex and has been hypothesized to be the locus of odor object formation. However, the PCX shows a distributed odorant representation that contrasts sharply with the topographical representation typically seen in the other primary sensory cortices. In this article, we explore an alternative organizational principle for the PCX based on where neurons are sending their output, rather than where these neurons are receiving their input. The piriform cortex (PCX) is the largest component of the olfactory cortex and is hypothesized to be the locus of odor object formation. The distributed odorant representation found in PCX contrasts sharply with the topographical representation seen in other primary sensory cortices, making it difficult to test this view. Recent work in PCX has focused on functional characteristics of these distributed afferent and association fiber systems. However, information regarding the efferent projections of PCX and how those may be involved in odor representation and object recognition has been largely ignored. To investigate this aspect of PCX, we have used the efferent pathway from mouse PCX to the orbitofrontal cortex (OFC). Using double fluorescent retrograde tracing, we identified the output neurons (OPNs) of the PCX that project to two subdivisions of the OFC, the agranular insula and the lateral orbitofrontal cortex (AI-OPNs and LO-OPNs, respectively). We found that both AI-OPNs and LO-OPNs showed a distinct spatial topography within the PCX and fewer than 10% projected to both the AI and the LO as judged by double-labeling. These data revealed that the efferent component of the PCX may be topographically organized. Further, these data suggest a model for functional organization of the PCX in which the OPNs are grouped into parallel output circuits that provide olfactory information to different higher centers. The distributed afferent input from the olfactory bulb and the local PCX association circuits would then ensure a complete olfactory representation, pattern recognition capability, and neuroplasticity in each efferent circuit.
Coeducation, academic performance, and subject choice: evidence from quasi-random classroom assignments

ABSTRACT I study the effect of coeducation on academic performance and science course enrollment using student-level data from a South Korean high school that, at the beginning of each academic year, quasi-randomly assigned students to either single-sex or coeducation classrooms. This paper presents two main findings. First, among girls with high achievements in Korean, coeducation increases the Korean exam scores by 0.11 standard deviations. Second, coeducation increases a girl's probability of enrolling in Physics, a math-intensive and boy-dominated science subject, by 71%, and increases a boy's probability of taking Biology by 34%.
Stream Networks and Long-Term Surface Uplift in the New Madrid Seismic Zone

Stream networks are sensitive to low rates of surface uplift and can be used to decipher the history of large earthquakes even where faults do not rupture the surface, as in intraplate seismic zones. Statistical analysis of alluvial network data from topographic maps in the New Madrid seismic zone, in the central United States, shows that stream-segment gradients deviate the most from an estimated natural stream profile where surface uplift is greatest. Evidence of cumulative deformation distilled from stream network patterns represents at least several meters of differential surface uplift during Holocene time, which suggests that more than one cycle of surface deformation occurred.
Corporate Tax Games with Cross‐Border Externalities from Public Infrastructure

We construct a model of corporate tax competition in which governments also use public infrastructure investment to attract foreign direct investment, thus enhancing their tax bases. In doing so, we allow for cross-border infrastructural externalities. Depending on the externality, governments are shown to strategically over- or underinvest in infrastructure. We also examine how tax cooperation influences investment in infrastructure and find that welfare may be lower under tax cooperation than under tax competition; this is the case when infrastructure is very effective in raising the tax base and generates a large negative cross-border externality. (JEL F23, H40)
Expression of chemokine by human coronary‐artery and umbilical‐vein endothelial cells and its regulation by inflammatory cytokines

BackgroundActivation of the endothelium is a critical event in the process of inflammation and is associated with the production of chemokines. ObjectiveTo evaluate the proinflammatory cytokine‐induced chemokine repertoire of human coronary‐artery endothelial cells (HCAEC) both at the messenger RNA (mRNA) level and at protein level in direct comparison with that of human umbilical‐vein endothelial cells (HUVEC). MethodsHuman coronary‐artery and human umbilical‐vein endothelial cells were obtained commercially and experimental data were derived from cell cultures between passage levels 3 through 6. Supernatant fluids from cytokine [tumor necrosis factor‐α (TNF‐α), interleukin‐1‐α, and anti‐TNF R55] stimulated endothelial cell cultures were used to study chemokine release. Sandwiched ELISA assays, obtained commercially, were used to estimate cell culture supernatant fluid levels of the selected chemokines: monocytic chemotactic protein‐1, regulated upon activated normal T cells expressed and secreted, interleukin‐8, transforming growth factor‐β‐2 (TGF‐β2), and gamma interferon protein‐10. Expression of messenger RNA was determined using selected labeled riboprobes (32P UTP) in a ribonuclease protection assay using total cellular mRNA. ResultsUpon in‐vitro stimulation with TNF‐α and interleukin‐1‐α, production of regulated‐upon‐activated‐normal‐T‐cells expressed and secreted (RANTES) protein by HCAEC was significantly increased relative to that by HUVEC, the greatest effect being found with interleukin‐1‐α. The opposite effect, however, was noted for levels of monocytic‐chemotactic‐protein‐1 protein, which were detected in HUVEC at significantly higher levels than they were in HCAEC challenged by those cytokines. Production of gamma interferon‐inducible protein‐10 (γIP‐10) by HUVEC was induced by TNF‐α and interleukin‐1‐α, whereas only a modest induction by interleukin‐1‐α was seen in HCAEC. TGF‐β‐2 protein was constitutively expressed in HCAEC but not in HUVEC. Expression of mRNA was analyzed by the ribonuclease‐protection assay. RANTES mRNA was expressed in HCAEC from 3 h through 48 h after treatment with TNF‐α, whereas only a modest induction of RANTES was expressed in HUVEC 24 h and 48 h after treatment with TNF‐α. Monocytic‐chemotactic‐protein‐1 mRNA was constitutively expressed by both types of cell, but the basal levels in HCAEC was significantly higher than in HUVEC. HCAEC constitutively expressed both TGF‐β‐1 and TGF‐β‐2 mRNA, whereas HUVEC constitutively expressed TGF‐β‐1 only. ConclusionOur data indicate that HCAEC and HUVEC express chemokines differently, which could contribute to or influence site‐specific recruitment of subsets of leukocytes.
Tumor resistance to apoptosis

One of the hallmarks of human cancers is the intrinsic or acquired resistance to apoptosis. Evasion of apoptosis may contribute to carcinogenesis, tumor progression and also to treatment resistance, since most current anticancer therapies including chemotherapy, radio‐ and immunotherapy primarily act by activating cell death pathways including apoptosis in cancer cells. Hence, a better understanding of the molecular mechanisms underlying tumor resistance to apoptotic cell death is expected to provide the basis for a rational approach to develop molecular targeted therapies. © 2008 Wiley‐Liss, Inc.
Cervical length assessment by ultrasound as a predictor of preterm labour—is there a role for routine screening?

Transvaginal ultrasonography has recently been shown to be an objective, reproducible and reliable method to assess the cervix and predict the risk of preterm delivery in high‐risk pregnancies. Assessment of the cervix includes cervical length measurement (CLM) and measurement of dilatation of the internal os in a dynamic functional examination. There is an inverse correlation between cervical length and the frequency of preterm delivery. The high negative predictive value avoids unnecessary interventions such as tocolysis or cerclage in high‐risk pregnancies. In contrast, a length of 25 mm or less at 28–30 weeks of gestation is associated with a significantly increased incidence of preterm delivery. Studies in women with high risk for preterm delivery, i.e. contractions, premature rupture of the membranes and history of preterm delivery, have shown a high sensitivity and a high positive predictive value, however in low‐risk groups they have failed to show a high sensitivity. From large observational studies in low‐risk populations we know that the 50th percentile of the cervical length is 35 mm at 24 weeks of gestation 3 . Advantages of CLM as a screening test include the fact that sonographical assessment of the cervix is a widely accepted and well‐standardised method, which requires only a relatively short period of training. Disadvantages of screening are two factors, the first being the low sensitivity of the test and the low prevalence of preterm deliveries in a low‐risk population, resulting in cut off values being set at a very low level (i.e. 5th percentile) in order to get acceptable specificity. Secondly, screening is only worthwhile if an effective preventive therapy is available. The debate about tocolysis and cerclage is not yet concluded. Therefore we would not currently recommend cervical length measurement as a screening tool—but as a routine method in high risk gravidas with or without symptoms. Further interest should be focused on scoring systems combining ultrasound with biochemical, endocrinological and maybe molecular cell methods such as the measurement of fetal DNA in maternal blood to prevent preterm deliveries in the general population.
Social network analysis of children with autism spectrum disorder: Predictors of fragmentation and connectivity in elementary school classrooms

Although children with autism spectrum disorder are frequently included in mainstream classrooms, it is not known how their social networks change compared to typically developing children and whether the factors predictive of this change may be unique. This study identified and compared predictors of social connectivity of children with and without autism spectrum disorder using a social network analysis. Participants included 182 children with autism spectrum disorder and 152 children without autism spectrum disorder, aged 5–12 years in 152 general education K-5 classrooms. General linear models were used to compare how age, classroom size, gender, baseline connectivity, diagnosis, and intelligence quotient predicted changes in social connectivity (closeness). Gender and classroom size had a unique interaction in predicting final social connectivity and the change in connectivity for children with autism spectrum disorder; boys who were placed in larger classrooms showed increased social network fragmentation. This increased fragmentation for boys when placed in larger classrooms was not seen in typically developing boys. These results have implications regarding placement, intervention objectives, and ongoing school support that aimed to increase the social success of children with autism spectrum disorder in public schools.
Acute glucose starvation activates the nuclear localization signal of a stress‐specific yeast transcription factor

In yeast, environmental conditions control the transcription factor Msn2, the nuclear accumulation and function of which serve as a sensitive indicator of nutrient availablity and environmental stress load. We show here that the nuclear localization signal (NLS) of Msn2 is a direct target of cAMP‐dependent protein kinase (cAPK). Genetic analysis suggests that Msn2‐NLS function is inhibited by phosphorylation and activated by dephosphorylation. Msn2‐NLS function is unaffected by many stress conditions that normally induce nuclear accumulation of full‐length Msn2. The Msn2‐NLS phosphorylation status is, however, highly sensitive to carbohydrate fluctuations during fermentative growth. Dephosphorylation occurs in >2 min after glucose withdrawal but the effect is reversed rapidly by refeeding with glucose. This response to glucose depletion is due to changes in cAPK activity rather than an increase in protein phosphatase activity. Surprisingly, the classical glucose‐sensing systems are not connected to this rapid response system. Our results further imply that generic stress signals do not cause short‐term depressions in cAPK activity. They operate on Msn2 by affecting an Msn5‐dependent nuclear export and/or retention mechanism.
Cancer hallmarks in induced pluripotent cells: New insights

Studies are beginning to emerge that demonstrate intriguing differences between human‐induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). Here, we investigated the expression of key members of the Nodal embryonic signaling pathway, critical to the maintenance of pluripotency in hESCs. Western blot and real‐time RT‐PCR analyses reveal slightly lower levels of Nodal (a TGF‐β family member) and Cripto‐1 (Nodal's co‐receptor) and a dramatic decrease in Lefty (Nodal's inhibitor and TGF‐β family member) in hiPSCs compared with hESCs. The noteworthy drop in hiPSC's Lefty expression correlated with an increase in the methylation of Lefty B CpG island. Based on these findings, we addressed a more fundamental question related to the consequences of epigenetically reprogramming hiPSCs, especially with respect to maintaining a stable ESC phenotype. A global comparative analysis of 365 microRNAs (miRs) in two hiPSC versus four hESC lines ultimately identified 10 highly expressed miRs in hiPCSs with >10‐fold difference, which have been shown to be cancer related. These data demonstrate cancer hallmarks expressed by hiPSCs, which will require further assessment for their impact on future therapies. J. Cell. Physiol. 225: 390–393, 2010. © 2010 Wiley‐Liss, Inc.
Correction of Alternative Splicing of Tau in Frontotemporal Dementia and Parkinsonism Linked to Chromosome 17*

Mutations in the human tau gene cause frontotemporal dementia and Parkinsonism associated with chromosome 17 (FTDP-17). One of the major disease mechanisms in FTDP-17 is the increased inclusion of tau exon 10 during pre-mRNA splicing. Here we show that modified oligonucleotides directed against the tau exon 10 splice junctions suppress inclusion of tau exon 10. The effect is mediated by the formation of a stable pre-mRNA-oligonucleotide hybrid, which blocks access of the splicing machinery to the pre-mRNA. Correction of tau splicing occurs in a tau minigene system and in endogenous tau RNA in neuronal pheochromocytoma cells and is specific to exon 10 of the tau gene. Antisense oligonucleotide-mediated exclusion of exon 10 has a physiological effect by increasing the ratio of protein lacking the microtubule-binding domain encoded by exon 10. As a consequence, the microtubule cytoskeleton becomes destabilized and cell morphology is altered. Our results demonstrate that alternative splicing defects of tau as found in FTDP-17 patients can be corrected by application of antisense oligonucleotides. These findings provide a tool to study specific tau isoforms in vivo and might lead to a novel therapeutic strategy for FTDP-17.