Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of hypobaric hypoxia on postural control.

BACKGROUND While the effects of accelerative forces on the vestibular system have been thoroughly investigated, the effects of hypobaric conditions on the postural system have attracted less attention. The purpose of the study was to investigate if postural control is affected by hypobaric hypoxia. HYPOTHESIS Moderate hypobaric hypoxia may reduce postural control. METHODS Subjective and multiple objective measurements of postural control with open and closed eyes were made in 16 military aircrew standing on a static balance platform before, during, and after exposure to an altitude chamber training profile with a maximum altitude of 25,000 ft. RESULTS No subjective dizziness and no clinical unsteadiness were noted. However, significant changes in body sway were found at the balance platform during hypobaric exposure at 18,000, 14,000 and 8000 ft compared with the baseline registrations. The relative increase in sway movements was greater in the eyes open condition compared with the eyes closed condition, and significant for movements in the anteroposterior plane but not in the lateral plane. Most sway parameters returned to pre-exposure values on return to ground level. CONCLUSIONS Acute hypobaric hypoxia, corresponding to the tested altitudes, influenced postural control primarily in the anteroposterior plane with eyes open. This is in agreement with other studies showing that vision is the first of the special senses to be altered by lack of oxygen.
Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice

The protective effect of dietary saturated fatty acids against the development of alcoholic liver disease has long been known, but the underlying mechanism is not completely understood. We examined the involvement of the adipocyte hormone adiponectin. Circulating adiponectin levels were significantly elevated by chronic ethanol administration to mice consuming a diet high in saturated fat. The increase in circulating adiponectin was associated with the activation a set of hepatic signaling pathways mediated through AMP‐activated protein kinase, PPAR‐α, and PPAR‐γ coactivator α, which in turn led to markedly increased rates of fatty acid oxidation, prevention of hepatic steatosis, and alleviation of liver enzyme changes. Furthermore, treatment of rat 3T3‐L1 adipocytes with saturated fatty acids (palmitic or stearic acids) in the presence of ethanol increased secretion of adiponectin and enhanced activity of a mouse adiponectin promoter. In conclusion, the protective action of saturated fat against the development of alcoholic fatty liver in mice is partially mediated through induction of adiponectin. The present findings suggest a novel paradigm for dietary fatty acids in the pathogenesis of alcoholic liver disease and provide a promising therapeutic strategy—nutritional modulation of adiponectin—in treating human alcoholic fatty liver disease. (HEPATOLOGY 2005.)
Purification and Characterization of a UDP-Glucosyltransferase Produced by Legionella pneumophila

ABSTRACT Legionella pneumophila is the agent of Legionnaires' disease. It invades and replicates within eukaryotic cells, including aquatic protozoans, mammalian macrophages, and epithelial cells. The molecular mechanisms of the Legionella interaction with target cells are not fully defined. In an attempt to discover novel virulence factors of L. pneumophila, we searched for bacterial enzymes with transferase activity. Upon screening ultrasonic extracts of virulent legionellae, we identified a uridine diphospho (UDP)-glucosyltransferase activity, which was capable of modifying a 45-kDa substrate in host cells. An approximately 60-kDa UDP-glucosyltransferase was purified from L. pneumophila and subjected to microsequencing. An N-terminal amino acid sequence, as well as the sequence of an internal peptide, allowed us to identify the gene for the enzyme within the unfinished L. pneumophila genome database. The intact gene was cloned and expressed in Escherichia coli, and the recombinant protein was purified and confirmed to possess an enzymatic activity similar to that of the native UDP-glucosyltransferase. We designated this gene ugt (UDP-glucosyltransferase). The Legionella enzyme did not exhibit significant homology with any known protein, suggesting that it is novel in structure and, perhaps, in function. Based on PCR data, an enzyme assay, and an immunoblot analysis, the glucosyltransferase appeared to be conserved in L. pneumophila strains but was absent from the other Legionella species. This study represents the first identification of a UDP-glucosyltransferase in an intracellular parasite, and therefore modification of a eukaryotic target(s) by this enzyme may influence host cell function and promote L. pneumophila proliferation.
Diagnosis and Management of Isolated Subsegmental Pulmonary Embolism: Review and Assessment of the Options

We assessed the potential safety of withholding treatment of pulmonary embolism (PE) limited to subsegmental branches. Literature review showed that untreated patients with mostly subsegmental PE had no fatal recurrences in 1 to 3 months and no nonfatal recurrences of PE in 3 months. Patients with suspected PE who had nondiagnostic ventilation/perfusion lung scans, adequate cardiorespiratory reserve or low or moderate clinical probability, and negative serial noninvasive leg tests were shown not to require treatment. It appears safe, therefore, to withhold treatment of subsegmental PE providing (1) pulmonary–respiratory reserve is good; (2) no evidence of deep venous thrombosis (DVT) on serial testing; (3) major risk factor for PE was transient and no longer present; (4) no history of central venous catheterization or atrial fibrillation; and (5) willingness to return for serial venous ultrasound. After fully informing patients, some may choose to be treated and some may choose not to be treated.
Mechanism of DNA segregation in prokaryotes: ParM partitioning protein of plasmid R1 co‐localizes with its replicon during the cell cycle

The parA locus of plasmid R1 encodes a prokaryotic centromere‐like system that mediates genetic stabilization of plasmids by an unknown mechanism. The locus codes for two proteins, ParM and ParR, and a centromere‐like DNA region (parC) to which the ParR protein binds. We showed recently that ParR mediates specific pairing of parC‐containing DNA molecules in vitro. To obtain further insight into the mechanism of plasmid stabilization, we examined the intracellular localization of the components of the parA system. We found that ParM forms discrete foci that localize to specific cellular regions in a simple, yet dynamic pattern. In newborn cells, ParM foci were present close to both cell poles. Concomitant with cell growth, new foci formed at mid‐cell. A point mutation that abolished the ATPase activity of ParM simultaneously prevented cellular localization and plasmid partitioning. A parA‐containing plasmid localized to similar sites, i.e. close to the poles and at mid‐cell, thus indicating that the plasmid co‐localizes with ParM. Double labelling of single cells showed that plasmid DNA and ParM indeed co‐localize. Thus, our data indicate that parA is a true partitioning system that mediates pairing of plasmids at mid‐cell and subsequently moves them to the cell poles before cell division.
Self-Assembly Kinetics of Microscale Components: A Parametric Evaluation

At the microscale, assembly by grasp and release is challenging. Self-assembly (SA) is an alternative component assembly method to significantly reduce assembly equipment costs. However, successful application of SA requires high assembly rates and high yield (few process errors). Prior modeling efforts describe SA process performance (yield and rate) for specific system configurations, but they do not use measurable process parameters and provide limited ability to predict the impact of process changes. In this paper, an experimental SA system was designed that controls process parameters independently while measuring SA outcomes. This system is used to evaluate a simple parameterization model for SA rate. The travel direction of the parts is varied to measure the path dependence of the assembly probability in the limit of low-impact velocity. Moreover, effects from changing part geometry are evaluated and accounted for in the model. Experimental results show a strong part-geometry dependence and minimal dependence on part arrival angle. This information is a key step toward a parametric kinetic model of capillary SA and complements previous SA process modeling efforts.
Butyrophilin 3A1 Plays an Essential Role in Prenyl Pyrophosphate Stimulation of Human Vγ2Vδ2 T Cells

Most human γδ T cells express Vγ2Vδ2 TCRs and play important roles in microbial and tumor immunity. Vγ2Vδ2 T cells are stimulated by self- and foreign prenyl pyrophosphate intermediates in isoprenoid synthesis. However, little is known about the molecular basis for this stimulation. We find that a mAb specific for butyrophilin 3 (BTN3)/CD277 Ig superfamily proteins mimics prenyl pyrophosphates. The 20.1 mAb stimulated Vγ2Vδ2 T cell clones regardless of their functional phenotype or developmental origin and selectively expanded blood Vγ2Vδ2 T cells. The γδ TCR mediates 20.1 mAb stimulation because IL-2 is released by β− Jurkat cells transfected with Vγ2Vδ2 TCRs. 20.1 stimulation was not due to isopentenyl pyrophosphate (IPP) accumulation because 20.1 treatment of APC did not increase IPP levels. In addition, stimulation was not inhibited by statin treatment, which blocks IPP production. Importantly, small interfering RNA knockdown of BTN3A1 abolished stimulation by IPP that could be restored by re-expression of BTN3A1 but not by BTN3A2 or BTN3A3. Rhesus monkey and baboon APC presented HMBPP and 20.1 to human Vγ2Vδ2 T cells despite amino acid differences in BTN3A1 that localize to its outer surface. This suggests that the conserved inner and/or top surfaces of BTN3A1 interact with its counterreceptor. Although no binding site exists on the BTN3A1 extracellular domains, a model of the intracellular B30.2 domain predicts a basic pocket on its binding surface. However, BTN3A1 did not preferentially bind a photoaffinity prenyl pyrophosphate. Thus, BTN3A1 is required for stimulation by prenyl pyrophosphates but does not bind the intermediates with high affinity.
Creating options for 3D-SIC testing

Three-dimensional stacked ICs hold the promise of heterogeneous integration, inter-die connections with increased performance at lower power dissipation, and increased yield and hence decreased product cost. However, all of the above can only become true if 3D-SICs can be properly tested for manufacturing defects. Companies have started to develop their test strategies for these products, and the outcome is largely dependent on (1) the necessity of test generation for specific new 3D defects, (2) the feasibility of access the test targets, and (3) the economic trade-offs involved. Test research is needed to create options for these challenges.
Comorbidity in ADHD: implications for research, practice, and DSM-V.

OBJECTIVE Since the introduction of DSM-III/III-R, clinicians and investigators have shown increasing interest in the study of conditions comorbid with attention-deficit hyperactivity disorder (ADHD). Better understanding ADHD comorbidity patterns is needed to guide treatment, research and future classification approaches. METHOD The ADHD literature from the past 15 years was reviewed to (1) explore the most prevalent patterns of ADHD comorbidity; (2) examine the correlates and longitudinal predictors of comorbidity; and (3) determine the extent to which comorbid patterns convey unique information concerning ADHD etiology, treatment and outcomes. To identify potential new syndromes, the authors examined comorbid patterns based on eight validational criteria. RESULTS The largest available body of literature concerned the comorbidity with ADHD and conduct disorder/aggression, with a substantially smaller amount of data concerning other comorbid conditions. In many areas the literature was sparse, and pertinent questions concerning comorbidity patterns remain unexplored. Nonetheless available data warrant the delineation of two new subclassifications of ADHD: (1) ADHD aggressive subtype, and (2) ADHD, anxious subtype. CONCLUSIONS Additional studies of the frequency of comorbidity and associated factors are greatly needed to include studies of differential effects of treatment of children with various comorbid ADHD disorders, as well as of ADHD children who differ on etiological factors.
Identification of Multiple Genes Encoding Membrane Proteins with Undecaprenyl Pyrophosphate Phosphatase (UppP) Activity in Escherichia coli*

The bacA gene product of Escherichia coli was recently purified to near homogeneity and identified as an undecaprenyl pyrophosphate phosphatase activity (El Ghachi, M., Bouhss, A., Blanot, D., and Mengin-Lecreulx, D. (2004) J. Biol. Chem. 279, 30106–30113). The enzyme function is to synthesize the carrier lipid undecaprenyl phosphate that is essential for the biosynthesis of peptidoglycan and other cell wall components. The inactivation of the chromosomal bacA gene was not lethal but led to a significant, but not total, depletion of undecaprenyl pyrophosphate phosphatase activity in E. coli membranes, suggesting that other(s) protein(s) should exist and account for the residual activity and viability of the mutant strain. Here we report that inactivation of two additional genes, ybjG and pgpB, is required to abolish growth of the bacA mutant strain. Overexpression of either of these genes, or of a fourth identified one, yeiU, is shown to result in bacitracin resistance and increased levels of undecaprenyl pyrophosphate phosphatase activity, as previously observed for bacA. A thermosensitive conditional triple mutant ΔbacA,ΔybjG,ΔpgpB in which the expression of bacA is impaired at 42 °C was constructed. This strain was shown to accumulate soluble peptidoglycan nucleotide precursors and to lyse when grown at the restrictive temperature, due to the depletion of the pool of undecaprenyl phosphate and consequent arrest of cell wall synthesis. This work provides evidence that two different classes of proteins exhibit undecaprenyl pyrophosphate phosphatase activity in E. coli and probably other bacterial species; they are the BacA enzyme and several members from a superfamily of phosphatases that, different from BacA, share in common a characteristic phosphatase sequence motif.
Extracolonic findings at CT colonography: evaluation of prevalence and cost in a screening population.

BACKGROUND & AIMS To assess the prevalence and spectrum of extracolonic findings in a screening population undergoing computed tomography colonography (CTC), and to evaluate the short-term direct medical costs incurred from subsequent radiologic follow-up evaluation. METHODS Six hundred and eighty-one asymptomatic patients undergoing colonoscopy screening consented to a CTC examination. Extracolonic CT findings were classified into high, medium, and low importance. Clinical and radiologic follow-up, missed lesions, and outcomes were assessed by chart review (time interval, 410-1513 days; median, 913 days). Short-term direct medical costs of radiologic follow-up were determined based on Medicare 2002 reimbursement rates. RESULTS Extracolonic findings were found commonly. These were categorized as high clinical importance in 71 (10%) individuals, as medium importance in 183 individuals (27%), and as low importance in 341 individuals (50%). Subsequent medical or surgical interventions resulted from these findings in 9 of the 681 patients (1.3%). Costs of subsequent radiologic follow-up studies were calculated as $23,380.59 (average added costs per CTC examination $34.33). CONCLUSIONS CTC commonly detects extracolonic findings that can be considered clinically important when applied to an asymptomatic screening population. Although such incidental findings add benefit to the screening intervention, moderate incremental costs are incurred based on additional radiologic procedures generated during short-term follow-up.
Ethnic differences in lipoprotein subclasses in obese adolescents: importance of liver and intraabdominal fat accretion.

BACKGROUND Recently, the deleterious metabolic effects of visceral fat [visceral adipose tissue (VAT)] deposition were challenged, and liver fat emerged as having a key independent role in the modulation of cardiometabolic risk factors. OBJECTIVE We explored the relation between liver fat content and VAT in 3 ethnic groups and evaluated whether the ethnic differences in the distributions of lipoprotein concentrations and sizes were associated with the hepatic fat fraction (HFF), VAT, or both. DESIGN In a multiethnic group of 33 white, 33 African American, and 33 Hispanic obese adolescents with normal glucose tolerance, we measured VAT and HFF by using magnetic resonance imaging. Fasting lipoprotein particle number and size were measured by using nuclear magnetic resonance spectroscopy. To assess the association between VAT and HFF, we categorized VAT into tertiles. RESULTS In each ethnic group, HFF values increased between successive tertiles of VAT. After multivariate adjustment and in comparison with the 2 other groups, African Americans showed lower triglyceride (P = 0.001) and higher HDL (P = 0.03) concentrations, lower concentrations of total (P = 0.007), large (P = 0.005), and medium (P lt 0.0001) VLDL, but higher concentrations of large HDL particles (P = 0.01) and larger HDL (P = 0.005). In multivariate linear models, independent of ethnicity, VAT was a significant predictor for large HDL (P = 0.003) and total small LDL (P = 0.001) concentrations, whereas HFF significantly predicted large VLDL (P = 0.03) concentrations. CONCLUSION Liver fat accretion, independent of VAT, may play a role in the ethnic differences seen in large VLDL particles. This trial was registered at clinicaltrials.gov as NCT00536250.
Hirudin anticoagulation allows more rapid determination of P2Y12 inhibition by the VerifyNow P2Y12 assay

Summary VerifyNow (VN) P2Y12 is a point-of-care assay used to assess response to P2Y12 inhibitors. Sodium citrate (citrate) is the standard anticoagulant used for this assay but requires a pre-incubation period. Hirudin is an alternative anticoagulant for platelet function studies that maintains physiological divalent cation levels. We investigated whether hirudin anticoagulation might allow more rapid testing of P2Y12 inhibition at the time of percutaneous coronary intervention (PCI). Blood was collected from the arterial sheath of aspirin-treated patients undergoing elective, urgent or emergency coronary angiography ± PCI and aliquots were anticoagulated with either citrate or hirudin. For each anticoagulant, VN P2Y12 was performed both immediately and after 20 minutes. A total of 98 patients were included in this study following pre-treatment with clopidogrel (n = 88), prasugrel (n = 6) or no P2Y12 inhibitor (n = 4). PRU with hirudin immediately (PRU_H_Imm) and PRU with citrate 20 minutes post sampling (PRU_C_20) were very strongly correlated (R = 0.95) though PRU_H_Imm tended to be lower than PRU_C_20 so that optimal correlation was estimated by the equation PRU_H_Imm = 0.95 x PRU_C_20 (p < 0.001). Bland-Altman plots showed good agreement between PRU_H_Imm and (0.95 x PRU_C_20). Platelet reactivity was more stable over the studied time course with hirudin as compared to citrate. We therefore conclude that VN P2Y12 with hirudin anticoagulation can be performed more rapidly and results are strongly correlated with delayed citrate measurements. Further studies are warranted to assess the utility of this method for improving clinical outcomes in patients undergoing PCI.
Maintenance treatment of preterm labor with the oxytocin antagonist atosiban. The Atosiban PTL-098 Study Group.

OBJECTIVES Patients admitted with an acute episode of preterm labor who respond to early intravenously administered tocolysis remain at risk of having subsequent episodes of preterm labor and preterm delivery. Several pharmacologic agents have been used in an attempt to reduce subsequent episodes of preterm labor, and all are associated with significant side effects. Atosiban, an oxytocin receptor antagonist, is effective in the treatment of an acute episode of preterm labor. This study was designed to compare the efficacy and safety of atosiban with those of placebo maintenance therapy in women with preterm labor who achieved uterine quiescence with intravenous atosiban. STUDY DESIGN A multicenter, double-blind, placebo-controlled trial was designed for patients in preterm labor who responded to early intravenous treatment with atosiban. Five hundred thirteen patients were randomly assigned to receive maintenance therapy, 252 to receive atosiban, and 251 to receive matching placebo. Maintenance therapy was administered as a continuous subcutaneous infusion, via pump, of 30 microg/min to the end of 36 weeks' gestation. The primary end point was the number of days from the start of maintenance therapy until the first recurrence of labor. A secondary end point was the percentage of patients receiving subsequent intravenous atosiban therapy. RESULTS The time (median) from the start of maintenance treatment to the first recurrence of labor was 32.6 days with atosiban and 27.6 days with placebo (P =.02). At least one subsequent intravenous atosiban treatment was needed by 61 atosiban patients (23%) and 77 placebo patients (31%). Except for injection site reactions, adverse event profiles of atosiban and placebo were comparable. There were 4 neonatal deaths reported in the atosiban group and 5 in the placebo group after the start of maintenance therapy. Infant outcomes (including birth weight) were comparable between maintenance and treatment groups. CONCLUSIONS Maintenance therapy with the oxytocin receptor antagonist atosiban can prolong uterine quiescence after successful treatment of an acute episode of preterm labor with atosiban. Treatment was well tolerated.
The p38 Mitogen-activated Kinase Pathway Regulates the Human Interleukin-10 Promoter via the Activation of Sp1 Transcription Factor in Lipopolysaccharide-stimulated Human Macrophages*

Interleukin-10 (IL-10), a pleiotropic cytokine that inhibits inflammatory and cell-mediated immune responses, is produced by a wide variety of cell types including T and B cells and monocytes/macrophages. Regulation of pro- and anti-inflammatory cytokines has been suggested to involve distinct signaling pathways. In this study, we investigated the regulation of the human IL-10 (hIL-10) promoter in the human monocytic cell line THP-1 following activation with lipopolysaccharide (LPS). Analysis of hIL-10 promoter sequences revealed that DNA sequences located between base pairs −652 and −571 are necessary for IL-10 transcription. A computer analysis of the promoter sequence between base pairs −652 and −571 revealed the existence of consensus sequences for Sp1, PEA1, YY1, and Epstein-Barr virus-specific nuclear antigen-2 (EBNA-2)-like transcription factors. THP-1 cells transfected with a plasmid containing mutant Sp1 abrogated the promoter activity, whereas plasmids containing the sequences for PEA1, YY1, and EBNA-2-like transcription factors did not influence hIL-10 promoter activity. To understand the events upstream of Sp1 activation, we investigated the role of p38 and extracellular signal-regulated kinase mitogen-activated protein kinases by using their specific inhibitors. SB202190 and SB203580, the p38-specific inhibitors, inhibited LPS-induced IL-10 production. In contrast, PD98059, a specific inhibitor of extracellular signal-regulated kinase kinases, failed to modulate IL-10 production. Furthermore, SB203580 inhibited LPS-induced activation of Sp1, as well as the promoter activity in cells transfected with a plasmid containing the Sp1 consensus sequence. These results suggest that p38 mitogen-activated protein kinase regulates LPS-induced activation of Sp1, which in turn regulates transcription of the hIL-10 gene.