Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Cis-Acting Elements in the 3′-Untranslated Region of the Dengue Virus Type 2 RNA That Modulate Translation and Replication*

Using the massively parallel genetic algorithm for RNA folding, we show that the core region of the 3′-untranslated region of the dengue virus (DENV) RNA can form two dumbbell structures (5′- and 3′-DBs) of unequal frequencies of occurrence. These structures have the propensity to form two potential pseudoknots between identical five-nucleotide terminal loops 1 and 2 (TL1 and TL2) and their complementary pseudoknot motifs, PK2 and PK1. Mutagenesis using a DENV2 replicon RNA encoding the Renilla luciferase reporter indicated that all four motifs and the conserved sequence 2 (CS2) element within the 3′-DB are important for replication. However, for translation, mutation of TL1 alone does not have any effect; TL2 mutation has only a modest effect in translation, but translation is reduced by ∼60% in the TL1/TL2 double mutant, indicating that TL1 exhibits a cooperative synergy with TL2 in translation. Despite the variable contributions of individual TL and PK motifs in translation, WT levels are achieved when the complementarity between TL1/PK2 and TL2/PK1 is maintained even under conditions of inhibition of the translation initiation factor 4E function mediated by LY294002 via a noncanonical pathway. Taken together, our results indicate that the cis-acting RNA elements in the core region of DENV2 RNA that include two DB structures are required not only for RNA replication but also for optimal translation.
How does the Schwann cell lineage form tumors in NF1?

Neurofibromas are benign tumors of peripheral nerve that occur sporadically or in patients with the autosomal dominant tumor predisposition syndrome neurofibromatosis type 1 (NF1). Multiple neurofibroma subtypes exist which differ in their site of occurrence, their association with NF1, and their tendency to undergo transformation to become malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy associated with NF1. Most NF1 patients carry a constitutional mutation of the NF1 tumor suppressor gene. Neurofibromas develop in these patients when an unknown cell type in the Schwann cell lineage loses its remaining functional NF1 gene and initiates a complex series of interactions with other cell types; these interactions may be influenced by aberrant expression of growth factors and growth factor receptors and the action of modifier genes. Cells within certain neurofibroma subtypes subsequently accumulate additional mutations affecting the p19ARF‐MDM2‐TP53 and p16INK4A‐Rb signaling cascades, mutations of other as yet unidentified genes, and amplification of growth factor receptor genes, resulting in their transformation into MPNSTs. These observations have been validated using a variety of transgenic and knockout mouse models that recapitulate neurofibroma and MPNST pathogenesis. A new generation of mouse models is also providing important new insights into the identity of the cell type in the Schwann cell lineage that gives rise to neurofibromas. Our improving understanding of the mechanisms underlying the pathogenesis of neurofibromas and MPNSTs raises intriguing new questions about the origin and pathogenesis of these neoplasms and establishes models for the development of new therapies targeting these neoplasms. © 2008 Wiley‐Liss, Inc.
Nuclear receptors as therapeutic targets in cholestatic liver diseases

Cholestasis results in intrahepatic accumulation of cytotoxic bile acids, which cause liver damage ultimately leading to biliary fibrosis and cirrhosis. Cholestatic liver injury is counteracted by a variety of adaptive hepatoprotective mechanisms including alterations in bile acid transport, synthesis and detoxification. The underlying molecular mechanisms are mediated mainly at a transcriptional level via a complex network involving nuclear receptors including the farnesoid X receptor, pregnane X receptor, vitamin D receptor and constitutive androstane receptor, which target overlapping, although not identical, sets of genes. Because the intrinsic adaptive response to bile acids cannot fully prevent liver injury in cholestasis, therapeutic targeting of these receptors via specific and potent agonists may further enhance the hepatic defence against toxic bile acids. Activation of these receptors results in repression of bile acid synthesis, induction of phases I and II bile acid hydroxylation and conjugation and stimulation of alternative bile acid export while limiting hepatocellular bile acid import. Furthermore, the use of nuclear receptor ligands may not only influence bile acid transport and metabolism but may also directly target hepatic fibrogenesis and inflammation. Many drugs already used to treat cholestasis and its complications such as pruritus (e.g. ursodeoxycholic acid, rifampicin, fibrates) may act via activation of nuclear receptors. More specific and potent nuclear receptor ligands are currently being developed. This article will review the current knowledge on nuclear receptors and their potential role in the treatment of cholestatic liver diseases.
Work correlates of back problems and activity restriction due to musculoskeletal disorders in the Canadian national population health survey (NPHS) 1994–5 data

OBJECTIVES To describe the prevalence of musculoskeletal problems in the Canadian working population and to determine cross sectional associations between such problems and work factors, particularly job strain and physical demand variables. METHODS The Canadian 1994 national population health survey (NPHS) sampled 4230 working men and 4043 working women (ages 18–64) who answered an abbreviated version of the job content questionnaire. Workers were classified into four strain categories: high, passive, active, and low. Outcomes were restricted activity due to musculoskeletal disorders and the diagnosis of a back problem (both yes or no). Survey weights were incorporated to allow for different probabilities of selection. Logistic regression analyses were carried out separately for women and men, controlling for sociodemographic factors. RESULTS Prevalence of chronic back problems diagnosed by a health practitioner was 14.5% among men and 12.5% among women. Men had a 6.6% prevalence of restricted activity due to musculoskeletal disorders, whereas the corresponding figure for women was 5.3%. Women, but not men, in high strain jobs were more likely to report both back problems (odds ratio (OR) 1.60, 95% confidence interval (95% CI) 1.14 to 2.28) and restricted activity (OR 1.98, 95% CI 1.16 to 3.48) compared with those in low strain jobs. High physical exertion was an independent predictor of back problems in both sexes. For both men and women, low social support at work and high job insecurity were independent predictors of restricted activity due to musculoskeletal disorders. Conversely, chronic back problems contributed to explanation of high job strain among women (OR 1.76, 95% CI 1.30 to 2.39) and high physical exertion among men (OR 1.39, 95% CI 1.09 to 1.77), whereas restricted activity due to musculoskeletal disorders contributed to explanation of high job insecurity in both sexes. CONCLUSIONS Associations of interest between work stressors and musculoskeletal problems in this cross sectional study provide evidence for physical and psychosocial factors both affecting disability and being affected by disability in a working population.
Sugar demand, not auxin, is the initial regulator of apical dominance

Significance It is commonly accepted that the plant hormone auxin mediates apical dominance. However, we have discovered that apical dominance strongly correlates with sugar availability and not apically supplied auxin. We have revealed that apical dominance is predominantly controlled by the shoot tip’s intense demand for sugars, which limits sugar availability to the axillary buds. These findings overturn a long-standing hypothesis on apical dominance and encourage us to reevaluate the relationship between hormones and sugars in this and other aspects of plant development. For almost a century the plant hormone auxin has been central to theories on apical dominance, whereby the growing shoot tip suppresses the growth of the axillary buds below. According to the classic model, the auxin indole-3-acetic acid is produced in the shoot tip and transported down the stem, where it inhibits bud growth. We report here that the initiation of bud growth after shoot tip loss cannot be dependent on apical auxin supply because we observe bud release up to 24 h before changes in auxin content in the adjacent stem. After the loss of the shoot tip, sugars are rapidly redistributed over large distances and accumulate in axillary buds within a timeframe that correlates with bud release. Moreover, artificially increasing sucrose levels in plants represses the expression of BRANCHED1 (BRC1), the key transcriptional regulator responsible for maintaining bud dormancy, and results in rapid bud release. An enhancement in sugar supply is both necessary and sufficient for suppressed buds to be released from apical dominance. Our data support a theory of apical dominance whereby the shoot tip’s strong demand for sugars inhibits axillary bud outgrowth by limiting the amount of sugar translocated to those buds.
Myelin oligodendrocyte glycoprotein‐DNA vaccination induces antibody‐mediated autoaggression in experimental autoimmune encephalomyelitis

One strategy to reestablish self tolerance in autoimmune diseases is based on the use of DNA vaccination to induce ectopic expression of the target autoantigen. We assessed the potential of vaccination with a DNA construct encoding the myelin oligodendrocyte glycoprotein (MOG), an important candidate autoantigen in multiple sclerosis, to induce tolerance and protect against experimental autoimmune encephalomyelitis (EAE). Unexpectedly, mice vaccinated with MOG‐DNA developed an exacerbated form of EAE when challenged with either MOG or an unrelated encephalitogen, myelin proteolipid protein. We demonstrate that this is due to the inability of DNA vaccination to tolerize the MOG‐specific T cell response and to the concomitant induction of a cytopathic MOG‐specific autoantibody response, which is pathogenic, enhancing demyelination, inflammation and disease severity. Our data suggest that tolerogenic strategies for autoimmune diseases based on DNA vaccination should be approached with caution, as the outcome is unpredictable.
Life at the Energetic Edge: Kinetics of Circumneutral Iron Oxidation by Lithotrophic Iron-Oxidizing Bacteria Isolated from the Wetland-Plant Rhizosphere

ABSTRACT Batch cultures of a lithotrophic Fe(II)-oxidizing bacterium, strain BrT, isolated from the rhizosphere of a wetland plant, were grown in bioreactors and used to determine the significance of microbial Fe(II) oxidation at circumneutral pH and to identify abiotic variables that affect the partitioning between microbial oxidation and chemical oxidation. Strain BrT grew only in the presence of an Fe(II) source, with an average doubling time of 25 h. In one set of experiments, Fe(II) oxidation rates were measured before and after the cells were poisoned with sodium azide. These experiments indicated that strain BrT accounted for 18 to 53% of the total iron oxidation, and the average cellular growth yield was 0.70 g of CH2O per mol of Fe(II) oxidized. In a second set of experiments, Fe(II) was constantly added to bioreactors inoculated with live cells, killed cells, or no cells. A statistical model fitted to the experimental data demonstrated that metabolic Fe(II) oxidation accounted for up to 62% of the total oxidation. The total Fe(II) oxidation rates in these experiments were strongly limited by the rate of Fe(II) delivery to the system and were also influenced by O2 and total iron concentrations. Additionally, the model suggested that the microbes inhibited rates of abiotic Fe(II) oxidation, perhaps by binding Fe(II) to bacterial exopolymers. The net effect of strain BrT was to accelerate total oxidation rates by up to 18% compared to rates obtained with cell-free treatments. The results suggest that neutrophilic Fe(II)-oxidizing bacteria may compete for limited O2 in the rhizosphere and therefore influence other wetland biogeochemical cycles.
Multislice computed tomography angiography screening for new aneurysms in patients with previously clip-treated intracranial aneurysms: Feasibility, positive predictive value, and interobserver agreement.

OBJECT Multislice computed tomography (CT) angiography may be useful for screening patients with intracranial aneurysms that are treated with clip occlusion. However, cobalt clips produce much more artifact on CT scans than titanium clips, which may hamper the evaluation of the image obtained at the clip site. METHODS The authors screened 415 patients with previously ruptured aneurysms that had been treated using cobalt clips. Screening was performed using multislice CT angiography. The feasibility of this modality for screening these patients (based on the complication risk, CT angiography quality, and artifact avoidance) and interobserver agreement were evaluated. Patients in whom the presence of an aneurysm was suspected based on results of CT angiography studies underwent digital subtraction (DS) angiography. False-negative and false-positive findings were recorded, and the positive predictive value (PPV) was calculated. Eight patients (1.9%) had allergies to the contrast material. The quality of the CT angiography image was suboptimal in 14%. In 52%, clip artifacts hampered evaluation of the clip site. In 65 patients who underwent DS angiography, there were nine false-positive and eight false-negative reports related to aneurysms that were either small, located at the clip site, or were infundibula. The PPV on a per-patient basis was 86% (95% confidence interval [CI] 75-94%); for aneurysms at the clip site it was 83% (95% CI 61-95%); and for aneurysms at different locations it was 91% (95% CI 81-97%). The interobserver agreement was good (kappa = 0.69; 95% CI 0.60-0.78). CONCLUSIONS Except for the evaluation of images from the clip site, CT angiography has good feasibility with good PPV and interobserver agreement. Drawbacks are that very small aneurysms can be missed and that visualization is poor at the clip site in patients in whom cobalt clips have been placed for occlusion. This second problem can be expected to resolve with the increasing use of titanium clips.
Survival and neurological outcomes after nasopharyngeal cooling or peripheral vein cold saline infusion initiated during cardiopulmonary resuscitation in a porcine model of prolonged cardiac arrest*

Objective:We have previously demonstrated that nasopharyngeal cooling initiated during cardiopulmonary resuscitation improves the success of resuscitation. In this study, we compared the effects of nasopharyngeal cooling with cold saline infusion initiated during cardiopulmonary resuscitation on resuscitation outcome in a porcine model of prolonged cardiac arrest. We hypothesized that nasopharyngeal cooling initiated during cardiopulmonary resuscitation would yield better resuscitation outcome when compared with cold saline infusion. Design:Randomized, prospective animal study. Setting:University-affiliated research laboratory. Subjects:Yorkshire-X domestic pigs (Sus scrofa). Interventions:Ventricular fibrillation was induced in 14 pigs weighing 38 ± 2 kg. After 15 mins of untreated ventricular fibrillation, cardiopulmonary resuscitation was performed for 5 mins before defibrillation. Coincident with the start of cardiopulmonary resuscitation, animals were randomly assigned to receive nasopharyngeal cooling with the aid of the RhinoChill Device (BeneChill, San Diego, CA) or cold saline infusion with 30 mL/kg 4°C saline. One hour after restoration of spontaneous circulation, surface cooling was begun with the aid of a water blanket in both groups and maintained for 4 hrs. Measurements and Main Results:Jugular vein temperature significantly decreased in animals subjected to nasopharyngeal cooling in comparison with those receiving cold saline infusion (p < .01). Core temperature, however, decreased only in animals receiving cold saline infusion (p < .01). Coronary perfusion pressure was significantly higher in the animals treated with nasopharyngeal cooling (p = .02). All seven animals treated with nasopharyngeal cooling were successfully resuscitated in contrast to only two animals resuscitated in the cold saline infusion group (p = .02). Conclusion:In this model, nasopharyngeal cooling initiated during cardiopulmonary resuscitation improved the success of resuscitation compared to cooling with cold saline infusion.
Stochastic Modeling of THz Indoor Radio Channels

Providing the basis for fast system simulations and the adequate design of upcoming THz communication systems, a novel stochastic 300 GHz indoor channel model is introduced. It combines both the modeling in time as well as in frequency domain in order to account for the significant frequency dispersion of ultra broadband THz channels. Not only amplitude, phase and temporal, but also spatial channel information is considered. That way, MIMO systems as well as novel antenna concepts can be simulated. Verified and calibrated frequency domain ray tracing simulations in an office scenario provide the data basis for the derivation of model parameters. Model channel realizations are tested against ray tracing predictions and channel measurements. A complete scenario-specific parameter set is given for the considered environment, so that the model can be implemented for further use and future THz communication links can be designed under consideration of realistic propagation conditions.
In-tunnel mobile communications deployment of an heterogeneous WLAN-WiMAX wireless network

Public transportation is vital in everyday life. As a consequence, the increasing need for intelligent surveillance systems over public transportation provides promising areas for wireless vehicular communication research for in-tunnel applications. This paper particularly emphasizes on tunnel implementation regarding to a prototype surveillance system on railway environments based on autonomous, smart monitoring devices that capture data only upon the occurrence of an incident, potentially dangerous for the passengers (like an explosion blast or the triggering of the fire detector). In this paper an attempt has been made to evaluate the performance of wireless vehicular communication inside a challenging tunnel environment after an emergency event. Due to the fact that extreme tunnel conditions (i.e. blind spots, intersymbol interference, NLOS) can cause major wireless network propagation failure, we develop a wireless hybrid network architecture consisted of IEEE 802.11b/g/e and IEEE 802.16e protocols. Furthermore this network was implemented in order to transmit the captured data from the monitoring devices of the train coaches to the Base Stations that are placed towards the metro stations. Finally, we use the OMNeT++ simulator tool for creating a simulation environment of the vehicular wireless network in order to compare the results with the experimental measurements.
Large‐scale preparation of Shiga toxin 2 in Escherichia coli for toxoid vaccine antigen production

Enterohemorrhagic Escherichia coli (EHEC) causes hemorrhagic colitis, and in more severe cases, a serious clinical complication called hemolytic uremic syndrome (HUS). Shiga toxin (Stx)is one of the factors that cause HUS. Serotypes of Stx produced by EHEC include Stx1 and Stx2. Although some genetically mutated toxoids of Stx have been developed, large‐scale preparation of Stx that is practical for vaccine development has not been reported. Therefore, overexpression methods for Stx2 and mutant Stx2 (mStx2) in E. coli were developed. The expression plasmid pBSK‐Stx2(His) was constructed by inserting the full‐length Stx2 gene, in which a six‐histidine tag gene was fused at the end of the B subunit into the lacZα fragment gene of the pBluescript II SK(+) vector. An E. coli MV1184 strain transformed with pBSK‐Stx2(His) overexpressed histidine‐tagged Stx2 (Stx2‐His) in cells cultured in CAYE broth in the presence of lincomycin. Stx2‐His was purified using TALON metal affinity resin followed by hydroxyapatite chromatography. From 1 L of culture, 68.8 mg of Stx2‐His and 61.1 mg of mStx2‐His, which was generated by site‐directed mutagenesis, were obtained. Stx2‐His had a cytotoxic effect on HeLa cells and was lethal to mice. However, the toxicity of mStx2‐His was approximately 1000‐fold lower than that of Stx2‐His. Mice immunized with mStx2‐His produced specific antibodies that neutralized the toxicity of Stx2 in HeLa cells. Moreover, these mice survived challenge with high doses of Stx2‐His. Therefore, the lincomycin‐inducible overexpression method is suitable for large‐scale preparation of Stx2 vaccine antigens.
Chemical heterogeneity of the striosomal compartment in the human striatum

The neurochemical organization of the striosomal compartment in the human striatum was analyzed by histochemical and immunohistochemical techniques applied to postmortem tissue from normal individuals. The striosomes were delineated by using the following markers: acetylcholinesterase (AChE), enkephalin (ENK), substance P (SP), calbindin‐D28k (CB), parvalbumin (PV), calretinin (CR), limbic system‐associated membrane protein (LAMP), choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), and NADPH‐diaphorase. Comparisons were made between striosomal boundaries, as outlined by each marker applied on adjacent sections, and particular attention was paid to possible variations in the chemical features of striosomes along the rostrocaudal extent of the striatum. The main findings of this study are as follows: 1) the striosomal compartment is composed of two chemically distinct domains: a core and a peripheral region; 2) the core is largely devoid of CB and displays a less intense staining for ENK and LAMP than the peripheral region; 3) although striosomes are largely devoid of AChE, the activity of this enzyme is slightly higher in the core than in the peripheral region; 4) the core and peripheral regions are weakly stained for PV and intensely stained for SP; 5) ChAT‐, CR‐ and NADPH‐diaphorase‐positive neurons are preferentially distributed in the peripheral region; 6) at rostral striatal levels, striosomes are largely devoid of TH, whereas the inverse is true caudally; and 7) at caudal striatal levels, the peripheral region of striosomes is intensely stained for CB and ChAT. These results demonstrate that the striosomes in human display a strikingly complex and heterogeneous chemical architecture. J. Comp. Neurol. 413:603–618, 1999. © 1999 Wiley‐Liss, Inc.