Miracle-dz/UniFAR-FTUs huggingface dataset:
Interactions and Localization of Escherichia coli Error-Prone DNA Polymerase IV after DNA Damage

ABSTRACT Escherichia coli's DNA polymerase IV (Pol IV/DinB), a member of the Y family of error-prone polymerases, is induced during the SOS response to DNA damage and is responsible for translesion bypass and adaptive (stress-induced) mutation. In this study, the localization of Pol IV after DNA damage was followed using fluorescent fusions. After exposure of E. coli to DNA-damaging agents, fluorescently tagged Pol IV localized to the nucleoid as foci. Stepwise photobleaching indicated ∼60% of the foci consisted of three Pol IV molecules, while ∼40% consisted of six Pol IV molecules. Fluorescently tagged Rep, a replication accessory DNA helicase, was recruited to the Pol IV foci after DNA damage, suggesting that the in vitro interaction between Rep and Pol IV reported previously also occurs in vivo. Fluorescently tagged RecA also formed foci after DNA damage, and Pol IV localized to them. To investigate if Pol IV localizes to double-strand breaks (DSBs), an I-SceI endonuclease-mediated DSB was introduced close to a fluorescently labeled LacO array on the chromosome. After DSB induction, Pol IV localized to the DSB site in ∼70% of SOS-induced cells. RecA also formed foci at the DSB sites, and Pol IV localized to the RecA foci. These results suggest that Pol IV interacts with RecA in vivo and is recruited to sites of DSBs to aid in the restoration of DNA replication. IMPORTANCE DNA polymerase IV (Pol IV/DinB) is an error-prone DNA polymerase capable of bypassing DNA lesions and aiding in the restart of stalled replication forks. In this work, we demonstrate in vivo localization of fluorescently tagged Pol IV to the nucleoid after DNA damage and to DNA double-strand breaks. We show colocalization of Pol IV with two proteins: Rep DNA helicase, which participates in replication, and RecA, which catalyzes recombinational repair of stalled replication forks. Time course experiments suggest that Pol IV recruits Rep and that RecA recruits Pol IV. These findings provide in vivo evidence that Pol IV aids in maintaining genomic stability not only by bypassing DNA lesions but also by participating in the restoration of stalled replication forks.
Helicobacter pylori Generates Superoxide Radicals and Modulates Nitric Oxide Metabolism*

During studies of the bactericidal action of nitric oxide (NO), we found that it reversibly inhibited the respiration of Escherichia coli and irreversibly inhibited the respiration of Helicobacter pylori. Peroxynitrite, a reaction product of NO and superoxide, irreversibly inhibited the respiration of both H. pylori and E. coli. H. pylori, but not E. coli, generated substantial amounts of superoxide radicals. These results suggest that NO directly inhibits the respiration of E. coli whereas it rapidly reacts with endogenously generated superoxide radicals in H. pylori. The resulting peroxynitrite inactivates the respiration of H. pylori.
The 1999 National Pressure Ulcer Prevalence Survey: a benchmarking approach.

OBJECTIVE Health care professionals are faced with the ongoing challenge of improving performance. From physicians and nurses to process improvement experts, health care professionals are discovering new approaches to increasing the overall effectiveness of procedures used in clinical areas. One way to collect data useful for benchmarking specific clinical practices is through the use of prevalence studies. DESIGN A 1-day pressure ulcer prevalence survey was performed in March 1999. Acute care facilities across the United States volunteered to participate in the data collection process. Patients' demographic information, pressure ulcer stages, locations, and support surfaces were noted. SETTING 356 acute care facilities. PARTICIPANTS 42,817 patients. RESULTS The overall pressure ulcer prevalence was 14.8%, with a nosocomial pressure ulcer prevalence of 7.1%. CONCLUSIONS Benchmarking is one of the tools that enables health care professionals to measure and identify inconsistencies in patient care practices. Understanding these inconsistencies enables the health care team to develop processes that are innovative and efficient. National pressure ulcer prevalence surveys provide a benchmark to evaluate an individual facility's care and treatment of patients at risk for pressure ulcer development. Success, however, lies in the health care professional's ability to take the information and apply it to clinical practice. Through the use of a benchmarking approach, performance gaps can be identified, processes can be put into place, and improved patient outcomes can be monitored and maintained.
Drosophila Mitf regulates the V-ATPase and the lysosomal-autophagic pathway

ABSTRACT An evolutionarily conserved gene network regulates the expression of genes involved in lysosome biogenesis, autophagy, and lipid metabolism. In mammals, TFEB and other members of the MiTF-TFE family of transcription factors control this network. Here we report that the lysosomal-autophagy pathway is controlled by Mitf gene in Drosophila melanogaster. Mitf is the single MiTF-TFE family member in Drosophila and prior to this work was known only for its function in eye development. We show that Mitf regulates the expression of genes encoding V-ATPase subunits as well as many additional genes involved in the lysosomal-autophagy pathway. Reduction of Mitf function leads to abnormal lysosomes and impairs autophagosome fusion and lipid breakdown during the response to starvation. In contrast, elevated Mitf levels increase the number of lysosomes, autophagosomes and autolysosomes, and decrease the size of lipid droplets. Inhibition of Drosophila MTORC1 induces Mitf translocation to the nucleus, underscoring conserved regulatory mechanisms between Drosophila and mammalian systems. Furthermore, we show Mitf-mediated clearance of cytosolic and nuclear expanded ATXN1 (ataxin 1) in a cellular model of spinocerebellar ataxia type 1 (SCA1). This remarkable observation illustrates the potential of the lysosomal-autophagy system to prevent toxic protein aggregation in both the cytoplasmic and nuclear compartments. We anticipate that the genetics of the Drosophila model and the absence of redundant MIT transcription factors will be exploited to investigate the regulation and function of the lysosomal-autophagy gene network.
High-Density Lipoprotein Cholesterol (HDL-C) Levels Independently Correlates With Cardiac Arrhythmias and Atrial Fibrillation

Objective: Acute coronary syndrome is frequently complicated by rhythm disturbances, yet any association between high-density lipoprotein (HDL) cholesterol levels and arrhythmias in the setting of non-ST-segment elevation myocardial infarction (non-STEMI) is uncertain. The goal of this study was to evaluate any association between HDL-cholesterol levels and arrhythmias in the setting of non-STEMI. Methods: Retrospective data from Phoenix Veterans Affair Medical Center records were utilized for our study. A total of 6881 patients were found who presented during 2000 to 2003 with non-STEMI with available fasting lipid panels collected within the first 24 hours of admission. Patients were followed for the development of rhythm disturbances up to 6 years after initial presentation, with a mean follow up of 1269 days. Results: We found that high triglycerides/HDL and low-density lipid/HDL ratios were predictive of arrhythmias. However, low HDL levels had strongest association with highest odds ratio (OR) for development of arrhythmias (for HDL <31 mg/dL, OR = 3.72, 95% confidence interval [CI] = 2.55-5.44, P < .05) in patients with diabetes and (for HDL < 31 mg/dL, OR = 3.69, 95% CI = 2.85-4.71, P < .05) in patients without diabetes. Using multivariate analysis adjusting for comorbidities, low HDL level remained independently associated with arrhythmias. Conclusions: Patients with low HDL levels during hospitalization with non-STEMI have a greater risk of developing cardiac rhythm disturbances independent of other risk factors. These data suggest a possible protective role of HDL in preventing arrhythmias in the setting of acute coronary syndrome.
Treatment endpoints for resistant port wine stains with a 755 nm laser

Laser therapy of port wine stains (PWS) resistant to pulsed dye laser is challenging and controversial. Based on the theory of selective photothermolysis, vessels in such lesions may be specifically targeted with the laser wavelength of 755 nm. There is much deeper penetration of the near‐infrared light and it is difficult to visualize laser‐induced changes within the deeper dermis. The recognition of an appropriate immediate endpoint response with this wavelength would be helpful. This is a clinical observations report. We present examples of an appropriate PWS tissue response endpoint based on our clinical observations in resistant PWS treated with a 755 nm laser at high fluences (40–100 J/cm2), 1.5‐ms pulse duration, with dynamic cooling device (DCD) cooling. Mild‐to‐moderate PWS lightening was associated with the immediate endpoint of a transient gray color that gradually evolved into persistent deep purpura within several minutes. We also discuss the clinical endpoints that represent undertreatment and overtreatment of PWS. It is important to attain, and maintain, the correct endpoint when treating PWS with this deeply penetrating near‐infrared laser at high fluences in order to (a) induce lesional lightening, and (b) avoid deep dermal burns that may produce scarring. Judicious use of the 755 nm laser can be beneficial for resistant PWS.
Breast Cancer After Mammary Augmentation

Augmentation mammoplasty has been said to reduce the risk for subsequent development of mammary gland carcinoma, but it may confer a worse prognosis should breast cancer develop. Nine patients who had breast cancer after augmentation mammoplasty were treated at the Ochsner Foundation Hospital and Clinic. The mean interval between augmentation and the development of a palpable mass was 6.8 years (range, 2 to 20 years). Four patients were treated with modified radical mastectomy, one was treated with radical mastectomy, and four were treated with tylectomy, axillary dissection, and radiotherapy. One of the four treated with tylectomy required salvage mastectomy. Reconstructions were done in all except one mastectomy patient. Five patients had stage I disease and four had stage II disease at the time of diagnosis. Over a mean follow-up of 4.75 years from the time of diagnosis of carcinoma of the breast, three of the four patients with stage II disease have either had recurrent disease or died of breast cancer, and one of the patients with stage I disease died with hepatic metastases. Mammography was not found to be useful for the detection of masses after augmentation mammoplasty. Needle aspirations were useful for diagnosis of nodal disease outside the breast, but not helpful in diagnosis of the breast lesion proper. Our analysis suggests that breast augmentation and the patient's psychologic considerations may delay the diagnosis of breast cancer. Additionally, patients may fare worse when breast cancer develops after mammary augmentation. We recommend preoperative mammography in most patients before mammary augmentation, particularly in those over the age of 30 years and those with a family history of breast cancer.
Gremlin localization and expression levels partially differentiate idiopathic interstitial pneumonia severity and subtype

Idiopathic pulmonary fibrosis (IPF) (histopathology of usual interstitial pneumonia, UIP) and non‐specific interstitial pneumonia (NSIP) are diseases characterized by loss of normal lung architecture and function. The differential diagnosis between IPF/UIP and NSIP may be difficult. The levels of bone morphogenetic protein (BMP)‐4 antagonist gremlin are up‐regulated in IPF/UIP. The present study was performed to clarify whether the localization or the mRNA expression of gremlin or BMP‐4 could be used in the differential diagnosis or assessment of severity of IPF/UIP and NSIP. Gremlin and BMP‐4 immunoreactivities were quantitated from 24 UIP and 12 NSIP lung specimens. Quantitative real‐time polymerase chain reaction analyses were performed to compare gremlin and BMP‐4 expression between UIP (n = 8) and NSIP (n = 5) biopsies. Immunohistochemical positivity and mRNA levels were correlated to lung function parameters. In IPF/UIP biopsies, gremlin was detected mainly in the thickened lung parenchyma, whereas in NSIP it was observed in the alveolar epithelium. BMP‐4‐positive (BMP‐4+) cells were detected solely in the alveolar wall. The percentage of gremlin‐positive area was higher in IPF/UIP (5.1 ± 0.6) than in NSIP (1.8 ± 0.7) (n = 36, p < 0.0001). Gremlin mRNA levels were higher in advanced UIP (p = 0.008) and NSIP (p = 0.007) biopsies than in the normal control lung. A negative correlation was found between the specific diffusion capacity corrected for alveolar volume (DLCO/VA) and gremlin mRNA levels (r = − 0.69, p = 0.007). The highest numbers of BMP‐4+ cells were found in NSIP biopsies. BMP‐4 mRNA levels correlated positively with forced vital capacity (r = 0.801, p < 0.0001) and diffusion capacity. Parenchymal gremlin immunoreactivity is thus suggestive of a UIP‐type interstitial pneumonia. Gremlin expression levels correlating negatively and BMP‐4 levels positively with disease severity support recent observations of a fibroprotective role for the BMPs. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Behavioural treatment for chronic low back pain.

BACKGROUND The treatment of chronic low back pain is not primarily focused on removing an underlying organic pathology, but at the reduction of disability through the modification of environmental contingencies and cognitive processes. Behavioural interventions are commonly used in the treatment of chronic (disabling) low back pain. OBJECTIVES The objective of this systematic review was to determine if behavioural therapy is more effective than reference treatments for chronic non-specific low back pain, and which type of behavioural treatment is most effective. SEARCH STRATEGY We searched the Medline, PsycLit databases, and the Cochrane Controlled Trials Register up to April 1999, Embase up to September 1999. We also screened references of identified randomised trials and relevant systematic reviews. SELECTION CRITERIA Only randomised trials on any type of behavioural treatment for non-specific chronic low back pain were included. DATA COLLECTION AND ANALYSIS Methodological quality assessment and data extraction was done by two reviewers independently. The magnitude of effect was assessed by computing a pooled effect size for each domain (i.e., behavioural outcomes, overall improvement, back pain specific and generic functional status, return to work, and pain intensity) using the random effects model. MAIN RESULTS Only 6 studies (25%) were high quality. There is strong evidence (level 1) that behavioural treatment has a moderate positive effect on pain intensity (pooled effect size 0.62; 95% CI 0.25, 0.98), and small positive effects on generic functional status (pooled effect size 0.35; 95% CI -0.04, 0.74) and behavioural outcomes (pooled effect size 0.40; 95% CI 0.10, 0.70) of chronic low back pain patients when compared to waiting list controls or no treatment. There is moderate evidence (level 2) that an additional behavioural component to a usual treatment program for chronic low back pain has no positive short-term effect on generic functional status (pooled effect size 0.31; 95% CI - 0.01, 0.64), pain intensity (pooled effect size 0.03; 95% CI - 0.30, 0. 36) and behavioural outcomes (pooled effect size 0.19; 95% CI - 0.08, 0.45). REVIEWER'S CONCLUSIONS Behavioural treatment seems to be an effective treatment for chronic low back pain patients, but it is still unknown what type of patients benefit most from what type of behavioural treatment.
Efficacy of Multidisciplinary Outpatient Management (MOM) Program in Long Term Heart Failure Care

Background: Heart failure (HF) management programs worldwide have reported conflicting outcomes in the past. Objectives: We sought to determine retrospectively whether the multidisciplinary outpatient management (MOM) program [heart failure clinic (HFC)], decreased readmission rates (RR), duration of hospital stay, and/or mortality in HF patients. Methods: Records of 138 HF patients who had their first encounter either as admission for HF at St. Agnes Hospital or visit to HFC during the period June 2005 through June 2006 were evaluated for outcomes through September 2007. Twenty-seven patients were followed in the HFC and 111 were in the non-HFC group. During follow up, 39 of the non-HFC group patients crossed over to the HFC group. All baseline parameters, except age (P = 0.006), were similar in both groups. Results: In the HFC group 4 patients had a total of 5 readmissions, whereas 85 patients had a total of 187 readmissions (P < 0.001) in the non-HFC group. Average lengths of hospitalization were 5.2 ± 4.8 days and 4.2 ± 3.2 days (P = 0.18) and the number of readmissions/patient/year was 0.3 and 1.45 (P < 0.001) in the HFC and non-HFC groups, respectively. In the subgroup analysis of cross overs (n = 39), there was a 60% reduction in the readmission rate after crossing over to the HFC group. The significance of decreased mortality in the HFC group could not be assessed due to the small sample size. Conclusion: The study suggests that the MOM program can significantly reduce RR secondary to HF.
Central venous catheter occlusion: a prospective, controlled trial examining the impact of a positive-pressure valve device.

BACKGROUND Central venous catheter (CVC) occlusion occurs frequently in children. This problem is often associated with disruption of intravascular therapy and monitoring. Multiple factors may predispose to catheter occlusion, but reflux of blood into the catheter lumen is a common factor. We hypothesized that use of a positive pressure valve device would reduce the incidence of catheter occlusion. METHODS In phase I of this sequential study design, newly placed CVCs were capped with a standard device. In Phase II, CVCs were capped with a positive-pressure valve device. Data collected included patient demographics, type of catheter, infusate, catheter duration, and complications. Partial and complete catheter occlusions were delineated. A user satisfaction survey was conducted. RESULTS There were 153 children (mean age 48.0 +/- 7.7 months) with 312 CVC lumens enrolled in the study. Mean catheter duration was 9.4 +/- 0.9 days. There were fewer complete occlusions in CVCs capped with the positive pressure valve device than with the standard device [6/161 (3.7%) vs 18/151 (11.9%) occlusions, respectively; p = . 012)]. There were no significant differences in partial occlusions, phlebitis, or catheter-related bloodstream infection between the 2 groups. CONCLUSIONS CVCs with a positive-pressure valve cap device have a lower incidence of complete catheter occlusion than those with a standard cap device.
Growth Hormone-induced Signal Transduction Depends on an Intact Ubiquitin System*

The growth hormone receptor (GHR) is a ubiquitinated cell surface protein. Ligand binding and receptor dimerization activate the cytosolic kinase Jak2. This event initiates signal transduction via STAT proteins. Expression of GHR in a Chinese hamster ovary (CHO) cell line, which exhibits a temperature-sensitive defect in ubiquitin conjugation (CHO-ts20), as well as in wild type cells (CHO-E36) has shown that endocytosis of the receptor requires an intact ubiquitin conjugation system (Strous G. J., van Kerkhof, P., Govers, R., Ciechanover A., and Schwartz, A. L. (1996) EMBO J. 15, 3806-3812). We have now examined the requirement for ubiquitin conjugation in growth factor-mediated signal transduction. In CHO-E36 and in CHO-ts20 cells at the permissive temperature, STAT proteins were activated in a growth factor-dependent fashion. However, no activation of STAT proteins was observed at the nonpermissive temperature in CHO-ts20 cells. Neither tyrosine phosphorylation of GHR nor of Jak2 was inhibited at the nonpermissive temperature. When tyrosine phosphorylation was inhibited following treatment with staurosporin, ubiquitination of the receptor proceeded normally. Furthermore, mutation of GHR phenylalanine-327, which prevents GHR endocytosis, inhibited receptor ubiquitination but allowed normal Jak/STAT-mediated signal transduction. Thus, these data provide evidence that the ubiquitin conjugation system is involved in the Jak/STAT signaling pathway, be it not at the initial stage(s) of Jak2 activity.
THE ACTION OF POLYMYXIN B AT THE FROG NEUROMUSCULAR JUNCTION

1 The effects of polymyxin B at the neuromuscular junction of the frog were studied by conventional electrophysiological and voltage clamp techniques. 2 At a concentration of 2.5 μg/ml polymyxin B produced neuromuscular blockade in 10 to 15 min and endplate potentials (e.p.ps) could be recorded. Resting membrane potential was unaffected. The neuromuscular block was characterized by a depressed e.p.p. quantal content (28 ± 7), which was similar to that determined from endplates exposed to 13 mm magnesium (23 ± 3), and a low e.p.p. quantal size, which was similar to that determined from endplates exposed to 3 μm (+)‐tubocurarine. 3 Polymyxin B (0.25 to 0.75 μg/ml) decreased mean miniature e.p.p. amplitude with little effect on frequency. 4 At a concentration of 5 μg/ml polymyxin B markedly shortened the duration of endplate currents (e.p.cs) and abolished the relationship between holding potential and the time to half‐decay at negative potentials greater than −;60 mV. This action is consistent with block of open acetylcholine activated ionic channels. 5 4‐Aminopyridine (20 μm) antagonized the depressed e.p.p. quantal content produced by polymyxin B but did not alter the shortened e.p.c. duration. 6 It is concluded that polymyxin B decreases quantal release and produces some degree of postjunctional receptor blockade and a marked and persistent blockade of acetylcholine activated channels. The latter action may explain the difficulty of reversal of polymyxin B‐induced neuromuscular blockade and its non‐competitive nature.
Relationship of language to the thinking process.

THE interrelationship of thought and language is an extremely complex problem. The disciplines of psychiatry, psychology, philology, and philosophy have grappled with the issue for many years, but the results have yielded no generally accepted resolution of the issue. In surveying the literature, this paper will attempt to present in cursory form a summary of the findings of the different disciplines. Psychologists and psychiatrists seem to group themselves around two poles of thought on the subject of thought and language. On one end of the continuum are those whose theories fit within the broad scope of the behaviorist school, which believes that thought is nothing more than subvocal speech.1Holding this general view are people such as Piaget,2Watson,1Vigotsky,3McCarthy,4Oleron,5Wells,6Bruner,7and Freud.8Some experimental findings on transposition behavior, concept formation, and abstracting