Miracle-dz/UniFAR-FTUs huggingface dataset:
Modular elements of the MLC 1f/3f locus confer fiber-specific transcription regulation in transgenic mice.

The two proteins encoded by the fast alkali myosin light chain (MLC) 1f/3f locus are developmentally regulated, muscle specific, and expressed exclusively in fast-twitch fibers. Their expression is independently regulated by two separate promoters and a downstream enhancer. Previous studies showed a reporter gene directed by the rat MLC If promoter and MLC enhancer to exhibit correct skeletal muscle-specific expression in transgenic mice during development and to be preferentially expressed in fast-twitch Type IIB fibers [Donoghue et al., (1991) J. Cell B.ol. 115:423-434]. The MLC 3f promoter also directed muscle-specific expression of a CAT reporter gene in adult transgenic mice and showed little dependence upon the enhancer. Here, we show that the MLC 3f promoter also directs transgene expression in the fast-twitch fibers of adult skeletal muscle, but almost exclusively to fiber Types IIA and IIX. MLC 3f transgene expression occurs in only a subset of the fiber types that express the endogenous locus, indicating modular elements included in the transgene confer fiber-specific transcription regulation. MyoD protein was also found to be restricted to fiber Types IIA and IIX, providing evidence for its possible role in mediating fiber-specific gene expression.
Oxidative Stress Response in Liver, Kidney and Gills of Ctenopharyngodon Idellus (Cuvier & Valenciennes) Exposed To Chlorpyrifos

Study on the chronic effects of an organophosphate, chlorpyrifos inducing oxidative stress in freshwater culturable carp, Ctenopharyngodon idellus has been made on exposure to sub-lethal concentration (1.41μg/L and 2.44μg/L) of the pesticide for 15, 30 and 60 days. Antioxidants viz. catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione-s-transferase (GST) and lipid peroxidation (LPO) in the liver, kidney and gills of the fish were analyzed. Studies revealed that the enhanced productions of reactive oxygen species (ROS) lead to oxidative damage to lipids & proteins, and inhibit antioxidant defence system of fish. The activity of LPO has followed an increasing trend and a decline in the activity of CAT, SOD and GSH at both the concentrations throughout the experiment. However, no definite trend in the activity of GST has been observed. Prolonged exposure to chlorpyrifos enhanced ROS formation, finally resulted in oxidative damage to cell and inhibited antioxidant capacities in the fish tissues.
Pain Assessment: The Roles of Physician Certainty and Curiosity

Undertreatment of pain is common even when caused by serious illness. We examined whether physician–patient communication (particularly language indicating physician certainty) was associated with incomplete (i.e., premature closure) of pain assessment among patients with serious illness. Standardized patients (SPs) trained to portray patients with serious illness conducted unannounced, covertly audio-recorded visits to 20 consenting family physicians and 20 medical specialists. We coded extent of pain assessment, physician voice tone, and a measure of the degree to which physicians explored and validated patient concerns. To assess physician certainty, we searched transcripts for use of words that conveyed certainty using the Linguistic Inquiry and Word Count program. SP role fidelity was 94%, and few physicians were suspicious that they had seen an SP (14% of visits). Regression analyses showed that physicians who used more certainty language engaged in less thorough assessment of pain (β = –0.48, p < .05). Conversely, physicians who engaged in more exploring and validating of patient concerns (β = 0.27, p < .05) had higher ratings on anxiety/concerned voice tone (β = 0.25, p <.01) and engaged in more thorough assessment of pain. Together, these three factors accounted for 38% of the variance in pain assessment. Physicians who convey certainty in discussions with patients suffering from pain may be more likely to close prematurely their assessment of pain. We found that expressions of physician concern and responsiveness (curiosity) were associated with superior pain assessment. Further study is needed to determine whether these associations are causal and mutable.
Ubiquitylation and activation of a Rab GTPase is promoted by a &bgr;2AR–HACE1 complex

ABSTRACT We and others have shown that trafficking of G-protein-coupled receptors is regulated by Rab GTPases. Cargo-mediated regulation of vesicular transport has received great attention lately. Rab GTPases, which form the largest branch of the Ras GTPase superfamily, regulate almost every step of vesicle-mediated trafficking. Rab GTPases are well-recognized targets of human diseases but their regulation and the mechanisms connecting them to cargo proteins are still poorly understood. Here, we show by overexpression and depletion studies that HACE1, a HECT-domain-containing ubiquitin ligase, promotes the recycling of the &bgr;2-adrenergic receptor (&bgr;2AR), a prototypical G-protein-coupled receptor, through a Rab11a-dependent mechanism. Interestingly, the &bgr;2AR in conjunction with HACE1 triggered ubiquitylation of Rab11a, as observed by western blot analysis. LC-MS/MS experiments determined that Rab11a is ubiquitylated on Lys145. A Rab11a-K145R mutant failed to undergo &bgr;2AR–HACE1-induced ubiquitylation and inhibited the HACE1-mediated recycling of the &bgr;2AR. Rab11a, but not Rab11a-K145R, was activated by &bgr;2AR–HACE1, indicating that ubiquitylation of Lys145 is involved in activation of Rab11a. Co-expression of &bgr;2AR–HACE1 also potentiated ubiquitylation of Rab6a and Rab8a, but not of other Rab GTPases that were tested. We report a novel regulatory mechanism of Rab GTPases through their ubiquitylation, with associated functional effects demonstrated on Rab11a. This suggests a new pathway whereby a cargo protein, such as a G-protein-coupled receptor, can regulate its own trafficking by inducing the ubiquitylation and activation of a Rab GTPase.
Mechanism of endothelium‐dependent relaxation induced by substance P in the coronary artery of the pig

1 Using front‐surface fluorometry of fura‐2‐loaded porcine coronary arterial strips with the endothelium intact, we investigated the mechanisms of vasorelaxation induced by substance P (SP). Fura‐2 fluorescence signals which indicated the cytosolic Ca2+‐concentration ([Ca2+]i), were observed to arise exclusively from the smooth muscle cells in these strips. 2 During the contractions induced by U46619 (100 nM), a thromboxane A2 analogue, an SP‐induced endothelium‐dependent, biphasic vasorelaxation was observed, which consisted of an initial rapid relaxation phase followed by a sustained phase, with a transient decrease in [Ca2+]i. Pretreatment with indomethacin (Ind) had no effect on the SP‐induced relaxation; however, pretreatment with NG‐nitro‐L‐arginine (l‐NOARG) partially, but significantly inhibited the decrease in both the [Ca2+]i and tension induced by SP; in addition, the sustained phase of SP‐induced relaxation was almost completely abolished. Thus, part of the relaxation was considered to be mediated by L‐NOARG‐sensitive relaxing factor (endothelium‐derived relaxing factor: EDRF). 3 During the 40 mM K+‐depolarization‐induced contraction which may eliminate the effects of endothelium‐derived hyperpolarizing factor (EDHF), the vasorelaxation induced by SP was completely inhibited by L‐NOARG. 4 During the vasorelaxation induced by SP, the [Ca2+]itension relationships shifted to the right of the contractions induced by either U46619 or high K+‐depolarization. 5 Using front‐surface fluorometry of fura‐2 loaded porcine aortic valvular strips, we examined the effects of SP on [Ca2+]i in endothelial cells in situ. SP induced a rapid increase in [Ca2+]i of endothelial cells in situ followed by a small sustained phase in normal PSS (5.9 mM K+). The increase in extracellular K+ had no apparent effect on the SP‐induced [Ca2+]i elevation of endothelial cells. 6 We thus conclude that: (1) SP‐induced vasorelaxation is mediated by an L‐NOARG‐sensitive factor (EDRF) and an L‐NOARG‐resistant factor; and (2) the first, rapid, phase of the relaxation is mediated by both factors while the sustained phase seems to be mediated mainly by EDRF. The underlying mechanisms of L‐NOARG‐resistant relaxation have yet to be elucidated, but EDHF appears to be a potentially contributing factor.
Surgical Management of Post-Traumatic Syringomyelia

Study Design. Systematic review. Objective. To determine the indications for surgical intervention and optimal surgical treatment technique for patients with post-traumatic syringomyelia and spinal cord tethering. Summary of Background Data. The proper management strategy for post-traumatic syringomyelia has not been established. Most modern surgical series have documented improvement in symptomatic patients who have an internal decompression of their syrinx. Several options exist and include shunting the syrinx (to the subarachnoid space or to either the pleural or peritoneal cavities) as well as spinal cord untethering (with or without expansile duraplasty). Methods. A systematic review of literature followed by expert panel consensus was performed. English language literature published between 1980 and 2010 was gathered to examine articles search was conducted using the search terms syringomyelia, syrinx, spinal cord injury, traumatic syringomyelia, post-traumatic syringomyelia. Case reports and articles examining syrinx due to other cause were excluded. Articles were graded for strength of evidence according to the GRADE approach. The evidentiary tables were reviewed and approved by all 4 authors, and disagreements were resolved by consensus. Results. The literature search yielded a total of 296 abstracts, and 22 articles were found to fulfill all the criteria specified above. All identified articles were of low or very low evidence levels. The reported incidence of post-traumatic syringomyelia is 0.5% to 4.5%; the incidence is twice as common in complete versus incomplete injuries. The literature consistently demonstrated that surgery post-traumatic syringomyelia is effective at arresting or improving motor deterioration, but not sensory dysfunction or pain syndromes. The literature does not support surgical intervention for incidental, asymptomatic syrinx. The literature does not support one surgical technique as superior for the treatment of post-traumatic syringomyelia. Conclusion. The literature supports and the consensus panel recommended that there is no indication for direct decompression at the time of initial injury specifically for the purpose of limiting future risk of syringomyelia. The literature supports and the consensus panel gave a strong recommendation for surgical intervention in the setting of motor neurologic deterioration as a consequence of post-traumatic syrinx/tethered cord. The panel gave a weak recommendation against surgical intervention for patients developing sensory loss/pain syndrome or for asymptomatic but expanding syrinx. Finally, the literature does not provide strong evidence to support the superiority of one surgical technique over the others; however, the consensus panel gave a weak recommendation that spinal cord untethering with expansile duraplasty is the preferred first-line surgical technique.
Genotype-dependent Molecular Evolution of Sheep Bovine Spongiform Encephalopathy (BSE) Prions in Vitro Affects Their Zoonotic Potential*

Background: The results of serial passage of BSE in sheep are unknown. Results: In vitro modeling shows a sheep genotype-dependent switch in prion protein type and loss of the ability to convert human prion protein. Conclusion: Molecular evolution of sheep BSE prions in vitro is genotype-dependent and affects zoonotic potential. Significance: Zoonotic risk might be predicted from cell-free modeling. Prion diseases are rare fatal neurological conditions of humans and animals, one of which (variant Creutzfeldt-Jakob disease) is known to be a zoonotic form of the cattle disease bovine spongiform encephalopathy (BSE). What makes one animal prion disease zoonotic and others not is poorly understood, but it appears to involve compatibility between the prion strain and the host prion protein sequence. Concerns have been raised that the United Kingdom sheep flock may have been exposed to BSE early in the cattle BSE epidemic and that serial BSE transmission in sheep might have resulted in adaptation of the agent, which may have come to phenotypically resemble scrapie while maintaining its pathogenicity for humans. We have modeled this scenario in vitro. Extrapolation from our results suggests that if BSE were to infect sheep in the field it may, with time and in some sheep genotypes, become scrapie-like at the molecular level. However, the results also suggest that if BSE in sheep were to come to resemble scrapie it would lose its ability to affect humans.
Perforin down-regulation and adhesion molecules activation in pulmonary sarcoidosis: an induced sputum and BAL study.

BACKGROUND Sarcoidosis is thought to be a T-helper type 1 cytokine-mediated disorder. Sputum induction has been proposed as a useful noninvasive method mainly for the assessment of airway diseases. However, it is unknown whether the balance of T-cytotoxic (Tc1) type 1 and Tc2 cells is altered in sarcoidosis. STUDY OBJECTIVES The primary aim of this study was to characterize the CD8+ T lymphocyte subpopulations in induced sputum from sarcoidosis patients, and to compare these subpopulations to those found in BAL fluid (BALF) from sarcoidosis patients. To further investigate the mechanism of the cytotoxic activity of CD8+ lymphocytes, we measured their perforin expression. Additionally, two adhesion molecules (CD62 and CD71), which are expressed on CD8+ T cells and may serve as novel immunologic markers, were detected. SETTINGS Department of Thoracic Medicine, University of Crete, and Department of Pneumonology, Democritus University of Thrace, Alexandroupolis, Greece. PATIENTS We prospectively studied 22 patients with sarcoidosis (median age, 48 years; age range, 25 to 65 years) and 10 healthy subjects (5 female and 5 male; median age, 39 years; age range, 26 to 60 years). INTERVENTIONS The stimulation of lymphocytes with phorbol 12-myristate 13-acetate was followed by the use of double immunocytochemical methods to identify CD8+ interferon (IFN)-gamma producing cells (ie, Tc1) and CD8+ interleukin-4 producing cells (ie, Tc2). MEASUREMENTS AND RESULTS We found a significant decrease in the prestimulation percentage of IFN-gamma-positive CD8+ T cells in the BALF (p = 0.001) and induced sputum (p = 0.001) of sarcoidosis patients compared to the number in samples from healthy control subjects. However, no significant difference was documented between lymphocyte subsets poststimulation. Decreased levels of perforin expression were found in BALF (p = 0.001) and induced sputum (p < 0.001) of sarcoidosis patients compared to those in control subjects. The adhesion molecules were significantly increased in both the BALF and induced sputum of the sarcoid population compared to those in healthy control subjects. CONCLUSIONS Our results suggest that inflammation could be effectively and noninvasively determined by using sputum induction in sarcoidosis patients. In addition, we have provided evidence suggesting the possibility that CD8+ lymphocytes might not play a major role in sarcoidosis.
A case–control study for evaluating the efficacy of mass screening program for lung cancer in miyagi prefecture, Japan

In Miyagi Prefecture, Japan, a mass screening program for lung cancer has been conducted since 1982 (miniature chest X‐ray for all screenees and sputum cytology for those with a smoking index ≥ 600) [smoking index 600 = 30 pack years, the average number of cigarettes smoked per day multiplied by the number of years of regular smoking]. Over 1500 lung carcinomas, including 250 roentgenographically occult lung tumors, were detected and treated up to 1999. In the current study, a nested case–control study was conducted in the population that was screened in 1989 to evaluate the efficacy of the screening program for lung cancer.
From Pyramids to Diamonds

In this article, the authors argue that offshoring of legal work from the United States has contributed to the fracturing of the long-established internal labor market arrangements in large U.S. law firms. Drawing on evidence from the United States and India on legal employment, the growth of offshoring, and the rapidly changing nature of work that is offshored, the authors contend that the changes in employment systems in law firms are likely to be permanent, in contrast to other researchers who suggest they are temporary adjustments to the financial crisis. As U.S. law firms are dismantling their internal labor market systems, Indian law firms are partially recreating them.
The unilateral and bilateral control of motor unit pairs in the first dorsal interosseous and paraspinal muscles in man

1 The discharges of two motor units were identified in an intrinsic hand muscle (first dorsal interosseous, FDI) or an axial muscle (lumbar paraspinals, PSP) in ten healthy subjects. Each motor unit was situated in the homologous muscle on either side of the body (bilateral condition) or in the same muscle (ipsilateral condition). The relationship between the times of discharge of the two units was determined using coherence analysis. 2 Motor unit pairs in the ipsilateral FDI showed significant coherence over the frequency bands 1‐10 Hz and 12‐40 Hz. Motor units in the ipsilateral PSP were significantly coherent below 5 Hz. In contrast there was no significant coherence at any frequency up to 100 Hz in the bilateral FDI condition and only a small but significant band of coherence below 2 Hz in the bilateral PSP condition. 3 Common drive to motor units at frequencies of < 4 Hz was assessed by cross‐correlation of the instantaneous frequencies of the motor units. A significantly higher coefficient was found in the ipsilateral FDI, ipsi‐ and bilateral PSP compared with shifted, unrelated data sets. This was not the case for the bilateral FDI condition. 4 The presence of higher frequency coherence (> 10 Hz) in the ipsilateral FDI condition and its absence in ipsilateral PSP is consistent with a more direct and influential cortical supply to the intrinsic hand muscles compared with the axial musculature. The presence of low frequency drives (< 4 Hz) in the bilateral PSP condition and its absence in the bilateral FDI condition is consistent with a bilateral drive to axial, but not distal, musculature by the motor pathways responsible for this oscillatory input.
Trends and antimicrobial resistance of pathogens causing bloodstream infections among febrile neutropenic adults with hematological malignancy.

BACKGROUND AND PURPOSE The microbiological spectrum in cancer patients with febrile neutropenia has changed over the past several decades in western countries. The growing incidence of antimicrobial resistance is an inevitable consequence of the widespread use of antibiotics in medical settings. The aim of this study was to clarify the trends and antimicrobial resistance among pathogens causing bloodstream infections in febrile neutropenic adults with hematological malignancies. METHODS The characteristics of pathogens causing bloodstream infection isolated from patients with febrile neutropenia who were treated at National Taiwan University Hospital from 1996 to 2001 were reviewed. A total of 1174 pathogens were isolated from 3093 admissions to a hematological ward during this period. Among them, 738 isolates were recovered from patients with febrile neutropenia. RESULTS The majority (93%) of these neutropenic febrile patients had underlying acute leukemia or lymphoma. Gram-negative bacteria accounted for 57% of isolated pathogens, followed by Gram-positive bacteria (32%), fungi (7%), and anaerobes (3%). In decreasing frequency, Escherichia coli (13%), Klebsiella pneumoniae (12%), Enterobacter cloacae (7%), Pseudomonas aeruginosa (6%), and Acinetobacter baumannii (5%) were the predominant Gram-negative bacteria, while coagulase-negative staphylococci (13%), viridans group streptococci (4%), and Staphylococcus aureus (4%) were the major Gram-positive pathogens. Two-thirds (20/30) of S. aureus isolates were resistant to oxacillin. No vancomycin-resistant enterococci were isolated. Resistance to cefotaxime was found in 63% of E. cloacae, 13% of K. pneumoniae and 10% of E. coli. Overall, 33% of E. coli and 13% of K. pneumoniae were resistant to ciprofloxacin. CONCLUSIONS This study indicates that the microbiological spectrum of microorganisms causing bloodstream infections in neutropenic febrile patients with hematological malignancies at National Taiwan University Hospital is different from western countries in that Gram-negative bacteria remain the predominant pathogens. Antimicrobial resistance among these pathogens is high and E. coli and K. pneumoniae isolates with resistance to third-generation cephalosporins and ciprofloxacin are increasing.
Measuring health-related quality of life in children with ESRD: performance of the generic and ESRD-specific instrument of the Pediatric Quality of Life Inventory (PedsQL).

BACKGROUND Minimal data exist to describe health-related quality of life in children with end-stage renal disease (ESRD). STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS 193 children aged 5 to 18 years with ESRD and 190 parents of children aged 2 to 18 years with ESRD at 4 pediatric nephrology centers across the United States. OUTCOMES & MEASUREMENTS Generic and disease-specific health-related quality of life. The Pediatric Quality of Life Inventory version 4.0 (PedsQL 4.0) Generic Core Scales encompass: (1) Physical Functioning (8 items), (2) Emotional Functioning (5 items), (3) Social Functioning (5 items), and (4) School Functioning (5 items). The PedsQL 3.0 ESRD Module encompasses: (1) General Fatigue (4 items), (2) About My Kidney Disease (5 items), (3) Treatment Problems (4 items), (4) Family and Peer Interaction (3 items), (5) Worry (10 items), (6) Perceived Physical Appearance (3 items), and (7) Communication (5 items). RESULTS Internal consistency reliability for the PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 ESRD Module was acceptable for both parent-proxy report and child self-report, with the exception of 1 parent-proxy report and 3 child self-report scales on the ESRD Module. The PedsQL Generic Core Scales differentiated between healthy children and children with ESRD, supporting discriminant validity. Intercorrelations between the PedsQL Generic Core Scales and the ESRD Module were in the medium to large range, supporting construct validity. A confirmatory factor analysis further supported construct validity of the ESRD Module. LIMITATIONS Test-retest reliability was not conducted, limited generalizability may exist given the age distribution of the children included, and imperfect agreement between child and parent-proxy reports. CONCLUSIONS Results support the feasibility, reliability, and validity of the PedsQL 4.0 Generic Core Scales in children with ESRD and provide initial support for the PedsQL 3.0 ESRD Module, although additional validation testing is warranted.