Miracle-dz/UniFAR-FTUs huggingface dataset:
TNFα‐induced ATF3 expression is bidirectionally regulated by the JNK and ERK pathways in vascular endothelial cells

ATF3 (Activating transcription factor 3), a member of the CREB/ATF family, can be induced by stress and growth factors in mammalian cells, and is thought to play an important role in the cardiovascular system. However, little is currently known about how the induction of ATF3 is regulated, except that the JNK pathway is involved. Here, we investigated the differential roles of the MAPK pathways involved in TNFα (tumour necrosis factor α)‐induced ATF3 expression in vascular endothelial cells. In human umbilical vein endothelial cells, the expression of constitutively active MKK7 (MAPK kinase 7) increased the number of ATF3‐positive cells, and dominant negative MKK7 suppressed the TNFα‐induced expression of ATF3, indicating a requirement for the JNK pathway. In contrast, the expression of constitutively active or dominant negative MEK1/2 (MAPK/ERK kinase 1/2) suppressed or enhanced TNFα‐mediated induction of ATF3, respectively. In support of this, the MEK1/2 specific inhibitor U0126 enhanced the expression of ATF3 induced by TNFα. Furthermore, the ERK pathway inhibits the TNFα‐mediated induction of ATF3 mRNA, but not its stability, suggesting the involvement of ERK activity in the transcriptional regulation of the ATF3 gene. Our results suggest that TNFα‐induced ATF3 gene expression is bidirectionally regulated by the JNK and ERK pathways in vascular endothelial cells.
A Tryptophan Neutral Radical in the Oxidized State of Versatile Peroxidase from Pleurotus eryngii

Versatile peroxidases are heme enzymes that combine catalytic properties of lignin peroxidases and manganese peroxidases, being able to oxidize Mn2+ as well as phenolic and non-phenolic aromatic compounds in the absence of mediators. The catalytic process (initiated by hydrogen peroxide) is the same as in classical peroxidases, with the involvement of 2 oxidizing equivalents and the formation of the so-called Compound I. This latter state contains an oxoferryl center and an organic cation radical that can be located on either the porphyrin ring or a protein residue. In this study, a radical intermediate in the reaction of versatile peroxidase from the ligninolytic fungus Pleurotus eryngii with H2O2 has been characterized by multifrequency (9.4 and 94 GHz) EPR and assigned to a tryptophan residue. Comparison of experimental data and density functional theory theoretical results strongly suggests the assignment to a tryptophan neutral radical, excluding the assignment to a tryptophan cation radical or a histidine radical. Based on the experimentally determined side chain orientation and comparison with a high resolution crystal structure, the tryptophan neutral radical can be assigned to Trp164 as the site involved in long-range electron transfer for aromatic substrate oxidation.
Complex I Deficiency Due to Selective Loss of Ndufs4 in the Mouse Heart Results in Severe Hypertrophic Cardiomyopathy

Mitochondrial complex I, the primary entry point for electrons into the mitochondrial respiratory chain, is both critical for aerobic respiration and a major source of reactive oxygen species. In the heart, chronic dysfunction driving cardiomyopathy is frequently associated with decreased complex I activity, from both genetic and environmental causes. To examine the functional relationship between complex I disruption and cardiac dysfunction we used an established mouse model of mild and chronic complex I inhibition through heart-specific Ndufs4 gene ablation. Heart-specific Ndufs4-null mice had a decrease of ∼50% in complex I activity within the heart, and developed severe hypertrophic cardiomyopathy as assessed by magnetic resonance imaging. The decrease in complex I activity, and associated cardiac dysfunction, occurred absent an increase in mitochondrial hydrogen peroxide levels in vivo, accumulation of markers of oxidative damage, induction of apoptosis, or tissue fibrosis. Taken together, these results indicate that diminished complex I activity in the heart alone is sufficient to drive hypertrophic cardiomyopathy independently of alterations in levels of mitochondrial hydrogen peroxide or oxidative damage.
A base-pairing interaction between U2 and U6 small nuclear RNAs occurs in > 150S complexes in HeLa cell extracts: implications for the spliceosome assembly pathway.

In mammalian cells, base pairing between the U2 and U6 small nuclear RNAs is required during pre-RNA splicing. We show by psoralen crosslinking of HeLa nuclear extract that U2.U6 base pairing occurs within abundant ribonucleoprotein complexes that sediment at > 150 S in glycerol gradients. All of the spliceosomal RNAs (U1, U2, U4, U5, and U6) cosediment with these large complexes, suggesting that they may be related to small nuclear RNA-containing structures called speckles/coiled bodies or snurposomes, which have been visualized in mammalian or amphibian nuclei, respectively. In contrast to nuclear extract, S100 extract, which is splicing-defective and lacks the > 150S complexes, does not contain base-paired U2.U6. However, U2.U6 base pairs form in S100 extract that has been made splicing-competent by supplementation with Ser/Arg-rich (SR) proteins, ATP, and an adenovirus splicing substrate. During splicing in supplemented S100 extract, U2.U6 base pairing precedes the appearance of splicing intermediates and occurs initially in an approximately 60S spliceosome complex but also in progressively larger (100-300 S) complexes. Possible functional relationships between the 60S spliceosome and the > 150S complexes are discussed.
Acute optic neuritis: its clinical features and their relation to prognosis for recovery of vision.

The clinical syndrome of acute optic neuritis has been known for many years though its causes are still uncertain. McAlpine, Lumsden, and Acheson (1965) state that the only common cause of unilateral optic neuritis is multiple sclerosis, but many others have been suggested (Woods Rowland, McAlpine Bjorkenheim, Despite this possible diversity of causes the syndrome usually has a stereotyped clinical picture. Blurring of vision in one, or more rarely both, eyes develops rapidly and usually increases over a few days, sometimes to complete loss of vision. Central vision is particularly affected. Pain in and around the affected eye, exaggerated by eye movement, is common. In any one attack final recovery of sight is usually good.
Separate Promoters from Proximal and Medial Control Regions Contribute to the Natural Killer Cell-specific Transcription of the Human FcγRIII-A (CD16-A) Receptor Gene*

The molecular events governing the differentiation pathway of natural killer (NK) cells are not well understood. The phenotype of mature NK cells is specified by the expression of the low affinity Fc receptor for IgG (human FcγRIII, CD16) encoded by the FcγRIII-A gene. Here we report that the Pprox promoter (−198/−10) of FcγRIII-A stimulated by its own intron enhancer (+10/+712) was only one of the cis-elements that target the expression of a reporter gene in the immature NK cell line, YT. The transcription start sites of the FcγRIII-A a2/3 and a5/6 splice alternatives in NK cells were mapped to the medial −1817/−850 FcγRIII-A control region. Two promoters, Pmed1 (−942/−850) and Pmed2 (−1376/−1123) resided in this region and controlled for the initiation of these transcript classes encoding the known FcγRIII-A receptor protein. Deletion mapping studies demonstrated that the 93 base pairs −942/−850 Pmed1 sequence was sufficient to confer cell type-specific expression in YT cells. The 5′ end of Pmed1 (−942 to −921) was required for full promoter function indicating the presence of an important sequence motif recognized by a YT-specific factor. Our data suggest that this motif might be a useful tool for subsequent identification of putative transcription factors uniquely active in YT and NK cells.
Two Distinct Mechanisms Mediate Acute μ-Opioid Receptor Desensitization in Native Neurons

Sustained stimulation of G-protein coupled receptors (GPCRs) leads to rapid loss of receptor function (acute desensitization). For many GPCRs including the μ-opioid receptor (MOR), an accepted mechanism for acute desensitization is through G-protein coupled receptor kinase (GRKs) mediated phosphorylation of the receptor, which facilitates the binding of β-arrestins (βarrs) to the receptor and then promotes endocytosis. However, the mechanism(s) that mediate acute desensitization have not yet been well defined in native neurons. This study used whole-cell patch clamp recording of G-protein coupled inward-rectifying potassium (GIRK) currents to assay MOR function and identify mechanisms of acute MOR desensitization in locus ceruleus (LC) neurons. The rate and extent of MOR desensitization were unaffected by βarr-2 knock-out. Disruption of GRK2 function via inhibitory peptide introduced directly into neurons also failed to affect desensitization in wild type or βarr-2 knock-outs. Inhibition of ERK1/2 activation alone had little effect on acute desensitization. However, when both GRK2-βarr-2 and ERK1/2 functions were disrupted simultaneously, desensitization of MOR was nearly abolished. Together, these results suggest that acute desensitization of MOR in native LC neurons is determined by at least two molecular pathways, one involving GRK2 and βarr-2, and a parallel pathway mediated by activated ERK1/2.
Characterization of a New Member of the Fatty Acid-binding Protein Family That Binds All-trans-retinol*

Cellular retinol-binding protein, type I (CRBP-I) and type II (CRBP-II) are the only members of the fatty acid-binding protein (FABP) family that process intracellular retinol. Heart and skeletal muscle take up postprandial retinol but express little or no CRBP-I or CRBP-II. We have identified an intracellular retinol-binding protein in these tissues. The 134-amino acid protein is encoded by a cDNA that is expressed primarily in heart, muscle and adipose tissue. It shares 57 and 56% sequence identity with CRBP-I and CRBP-II, respectively, but less than 40% with other members of the FABP family. In situ hybridization demonstrates that the protein is expressed at least as early as day 10 in developing heart and muscle tissue of the embryonic mouse. Fluorescence titrations of purified recombinant protein with retinol isomers indicates binding to all-trans-, 13-cis-, and 9-cis-retinol, with respective K d values of 109, 83, and 130 nm. Retinoic acids (all-trans-, 13-cis-, and 9-cis-), retinals (all-trans-, 13-cis-, and 9-cis-), fatty acids (laurate, myristate, palmitate, oleate, linoleate, arachidonate, and docosahexanoate), or fatty alcohols (palmityl, petrosenlinyl, and ricinolenyl) fail to bind. The distinct tissue expression pattern and binding specificity suggest that we have identified a novel FABP family member, cellular retinol-binding protein, type III.
Comparative Study of Clinical Staging of Oral Submucous Fibrosis with Qualitative Analysis of Collagen Fibers Under Polarized Microscopy.

BACKGROUND & OBJECTIVES Oral submucous fibrosis (OSMF) is a condition where excessive deposition of dense collagen fibers occurred in the connective tissue of oral mucosa. An alteration of collagen necessitates an in depth understanding of collagen in oral tissues as no breakthrough studies have been reported. T herefore the aim was to correlate the clinical, functional and histopathological staging and to analyze the polarization colors and thickness of the collagen fibers in different stages of OSMF using picrosirius red stain under polarizing microscopy so as to assess the severity of disease. METHODS The study was conducted in the department of Oral Pathology and Microbiology at Padm. Dr. D. Y Patil Dental and Hospital, Navi Mumbai, India (2012-13). A sample size was of a total 40 subjects, of which 30 patients had OSMF, and 10 were in control group. Clinical, functional and histopathological staging were done depending upon definite criteria. Collagen fibers were analyzed for polarizing colors and thickness. Further clinical, functional and histopathological stages as well as qualitative parameters of collagen fibers were compared. RESULTS The correlation between clinical and functional staging was not significant ( P >0.05) whereas the comparison of the functional staging with histopathological staging was more reliable ( P <0.01) as an indication to the severity of the disease rather than clinical staging. One-way ANOVA analysis showed highly significant correlation between functional staging and polarization colors and thickness of collagen fibers ( P <0.001). CONCLUSION The qualitative change in the collagen fibers of OSMF patients using polarized microscopy would help to assess its role in diagnostic evaluation, to determine the prognosis of the disease as well as to provide useful predictive treatment modalities to them.
Lecturers Experience Of Using Social Media In Higher Education Courses

This research paper presents lecturers experience of using social media in higher education courses. The research methodology used a survey approach. The research instrument was a questionnaire about lecturers experience of using social media in higher education courses. Thirty-one lecturers completed the questionnaire. The data were scored by frequency and percentage. The research results are as follows: 1) A slight majority of the lecturers were male. The largest age group was 3035 years old. The most commonly held highest degree was a Masters. The most common academic position they held was lecturer. The largest group was in the Department of Educational Technology and Communications. They had monthly incomes of 30,000 THB and over. They had experience of using social media, namely, Facebook, mostly through internet use on devices such as notebooks and desktops. 2) A majority of the lecturers had some experience using social media in higher education courses, mostly Facebook. However, they did not have teaching experience using social media in courses. The devices they used for facilitating social media use in courses were notebooks and desktops. Learners role in using social media in courses was searching. Lecturers roles were posting or creating, and commenting. Social media use in the courses was part of a blended approach that employed both regular and online instruction. The lecturers always searched for information and studied hard by themselves to cope with the problems of social media use in their courses and to enhance their skills in using social media in courses effectively.
Deep molecular divergence in the absence of morphological and ecological change in the Californian coastal dune endemic trapdoor spider Aptostichus simus

Aptostichus simus is a trapdoor spider endemic to the coastal dunes of central and southern California and, on morphological grounds, is recognized as a single species. Mitochondrial DNA 16S rRNA sequences demonstrate that most populations are fixed for the same haplotype and that the population haplotypes from San Diego County, Los Angeles County, Santa Rosa Island, and Monterey County are extremely divergent (6–12%), with estimated separation times ranging from 2 to 6 million years. A statistical cluster analysis of morphological features demonstrates that this genetic divergence is not reflected in anatomical features that might signify ecological differentiation among these lineages. The species status of these divergent populations of A. simus depends upon the species concept utilized. If a time‐limited genealogical perspective is employed, A. simus would be separated at the base into two genetically distinct species. This study suggests that species concepts based on morphological distinctiveness, in spider groups with limited dispersal capabilities, probably underestimate true evolutionary diversity.
Towards a stochastic model for integrated security and dependability evaluation

We present a new approach to integrated security and dependability evaluation, which is based on stochastic modelling techniques. Our proposal aims to provide operational measures of the trustworthiness of a system, regardless if the underlying failure cause is intentional or not. By viewing system states as elements in a stochastic game, we can compute the probabilities of expected attacker behavior, and thereby be able to model attacks as transitions between system states. The proposed game model is based on a reward-and cost concept. A section of the paper is devoted to the demonstration of how the expected attacker behavior is affected by the parameters of the game. Our model opens up for use traditional Markov analysis to make new types of probabilistic predictions for a system, such as its expected time to security failure.
What Do Transgender Patients Teach Us About Idiopathic Intracranial Hypertension?

ABSTRACT Idiopathic intracranial hypertension (IIH), a condition of raised intracranial pressure, is characterised by headaches and visual disturbances. Its pathogenesis is currently unknown; however, dysregulation of androgens may be implicated. Here, the authors present a case of a 22-year-old patient undergoing female-to-male (FTM) gender reassignment who developed IIH shortly after commencing testosterone therapy. This interesting case presents the possibility of androgens having a pathogenic role in IIH.
Leadership as boundary work in healthcare teams

This paper proposes that boundary work is inherent to leadership practices in healthcare settings, and explores this phenomenon in interprofessional healthcare teams. Specifically, the study focuses on leading through and across boundaries in four interprofessional healthcare teams operating in the area of mental health services. We give special consideration to the specific contexts of these teams, and address the boundaries that are constructed and managed in interactions. Our qualitative study revealed that leadership can be exercised by different members and at different levels within the teams, and that it involves managing the boundaries between (a) roles of different members of the leadership constellation, (b) leadership and clinical roles, (c) formal leaders and other members of the team, (d) different professions, (e) personal life experiences and professional work, and (f) the team and what members consider to be the environment. We identify different types of boundary work tactics that involve opening, closing, and contesting/negotiating boundaries. In addition, we address the potential consequences of each of these tactics. We consider the implications of our findings to leadership research and practice in healthcare contexts and beyond.
Lease/release: architectural support for scaling contended data structures

High memory contention is generally agreed to be a worst-case scenario for concurrent data structures. There has been a significant amount of research effort spent investigating designs which minimize contention, and several programming techniques have been proposed to mitigate its effects. However, there are currently few architectural mechanisms to allow scaling contended data structures at high thread counts. In this paper, we investigate hardware support for scalable contended data structures. We propose Lease/Release, a simple addition to standard directory-based MSI cache coherence protocols, allowing participants to lease memory, at the granularity of cache lines, by delaying coherence messages for a short, bounded period of time. Our analysis shows that Lease/Release can significantly reduce the overheads of contention for both non-blocking (lock-free) and lock-based data structure implementations, while ensuring that no deadlocks are introduced. We validate Lease/Release empirically on the Graphite multiprocessor simulator, on a range of data structures, including queue, stack, and priority queue implementations, as well as on transactional applications. Results show that Lease/Release consistently improves both throughput and energy usage, by up to 5x, both for lock-free and lock-based data structure designs.
Socioeconomic status and criminal sentencing: An empirical assessment of a conflict proposition.

The "conflict perspective" has generated considerable critical interest in the mechanisms of criminal sanctioning. Among the hypotheses generated by conflict criminology is the proposition that "when sanctions are imposed, the most severe sanctions will be imposed on, persons in the lowest social class" (Chambliss and Seidman, 1971:475). This paper affords an empirical test of that.proposition, which has been widely accepted as true despite the absence of substantial supporting evidence. Prison sentences received by 10,488 inmates for a total of seventeen specific offenses, within three southeastern states are examined. Product-moment correlations between a defendant's SES and the sentence received provide no support for the conflict proposition, and this conclusion is further strengthened when controls are introduced for "prior record" and demographic characteristics of the defendant. Multiple correlation and beta coefficients are also examined with similar conclusions. Implications for the explanation of criminal sanctioning institutions by conflict mechanisms are suggested.
Surgical complications in 550 consecutive cochlear implantation

Cochlear implantation is a safe and reliable method for auditory restoration in patients with severe to profound hearing loss. Objective To describe the surgical complications of cochlear implantation. Materials and Methods Information from 591 consecutive multichannel cochlear implant surgeries were retrospectively analyzed. All patients were followed-up for at least one year. Forty-one patients were excluded because of missing data, follow-up loss or middle fossa approach. Results Of 550 cochlear implantation analyzed, 341 were performed in children or adolescents, and 209 in adults. The mean hearing loss time was 6.3 ± 6.7 years for prelingual loss and 12.1 ± 11.6 years for postlingual. Mean follow-up was 3.9 ± 2.8 years. Major complications occurred in 8.9% and minor in 7.8%. Problems during electrode insertion (3.8%) were the most frequent major complication followed by flap dehiscence (1.4%). Temporary facial palsy (2.2%), canal-wall lesion (2.2%) and tympanic membrane lesion (1.8%) were the more frequent minor complications. No death occurred. Conclusion There was a low rate of surgical complications, most of them been successfully managed. These results confirm that cochlear implant is a safe surgery and most surgical complications can be managed with conservative measures or minimal intervention.