Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of Nuclear Transcription Factor NF-κB by Interleukin-1 Is Accompanied by Casein Kinase II-mediated Phosphorylation of the p65 Subunit*

In fibroblasts and hepatoma cells, interleukin-1 (IL-1) treatment results in the rapid nuclear accumulation of the transcription factor NF-κB, present largely as p65 (RelA)/p50 heterodimers. It is well established that this process is dependent in large part upon the phosphorylation and subsequent degradation of the cytosolic inhibitor IκB. We looked for other IL-1-induced modifications of NF-κB components and found that, in both cell types, IL-1 stimulation led, within minutes, to phosphorylation of both NF-κB p65 and p50. Phosphorylation of p65 was sustained for at least 30 min after addition of the cytokine and occurred principally upon serine residues. Immunoprecipitates of NF-κB complexes contained an associated protein kinase, the biochemical characteristics of which were indistinguishable from casein kinase II (CKII). Purified CKII efficiently phosphorylated p65 in vitro, apparently on the same major sites that became phosphorylated in intact IL-1-treated cells. Although IL-1 treatment caused little apparent stimulation of total cellular CKII activity, the fraction that was specifically associated with NF-κB complexes was markedly elevated by the cytokine. The association of CKII with NF-κB occurred in the cytoplasm, suggesting that this phosphorylation might be involved either in control of translocation of the activated complex or in modulation of its DNA binding properties.
What is ‘early onset dementia’?

There are two types of dementia with early onset: (i) presenile dementias; and (ii) senile dementias with early onset. Most patients who develop dementia before 65 years of age have Alzheimer's disease (AD). The remainder are likely to have vascular dementia (VaD), frontotemporal dementia, head injury, alcohol intoxication, or metabolic disorder. Presenile dementias, caused by frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration, usually occur in patients of presenile and are rarely seen in patients of senile age. Although the factors responsible for the accelarted onset of the illness are not fully known, genetic abnormalities appear to be important in some types of presenile dementia, such as frontotemporal dementia with parkinsonism linked to chromosome 17. Conversely, senile dementias such as sporadic AD and VaD commonly occur in patients of senile age. These disorders may also occur in patients of presenile age, although less frequently. Alzheimer's disease was originally classified as a ‘presenile dementia’. Since the 1980s, ‘senile dementia of Alzheimer type’ (SDAT) and ‘Alzheimer's disease’ have been considered to belong to the same pathological entity and both are now known as ‘dementia of Alzheimer's type (DAT)’ or merely ‘Alzheimer's disease’. Rapid progression of cognitive impairment with neuropsychological syndromes and neurological symptoms has been considered a characteristic of early onset AD. However, recently, neurological symptoms such as spastic paraparesis, seizures, and myoclonic convulsions have been reported to occur infrequently in early onset AD, although language problems and visuospatial dysfunctions are common. There are at least three dominant genes that have been identified in cases of familial Alzheimer's disease with early onset, namely the amyloid precursor gene (APP), and the genes encoding presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Therefore, genetic abnormalities are important factors contributing to the earlier onset of the illness. It is also important to investigate the pathophysiological mechanism in relation to genetic abnormalities, environmental factors, physical illnesses, and metabolic disturbances to understand the processes underlying the development of dementia with early onset.
Osteocyte viability after high-dose irradiation in the rabbit.

The effects of high-dose irradiation on the metabolism of osteocytes were examined with respect to RNA synthesis. A single 50-Gy dose of high-energy electron beam was given to the proximal tibia of rabbits. RNA synthesis by osteocytes was quantified by counting the silver grains on autoradiographs of cultured bone fragments, using 3H-cytidine as a tracer. At four, 12, and 52 weeks after irradiation, RNA synthesis by the irradiated osteocytes was 72, 62, and 79%, respectively, of that by nonirradiated osteocytes. The proportion of labeled osteocytes, conversely, was not reduced at four and 12 weeks, but was significantly reduced at 52 weeks after irradiation. The reduction in the RNA synthesis of osteocytes occurs fairly quickly, whereas reduction in the number of viable osteocytes occurs slowly as a delayed sequela. Histologic examination showed that the partial recovery of RNA synthesis observed at 52 weeks was attributable to the appearance of a fraction of new osteocytes, i.e., subendosteal apposition of new bone to the original, degrading cortex. These observations demonstrate the process of recovery from radiation damage.
Overproduction of human Cu/Zn‐superoxide dismutase in transfected cells: extenuation of paraquat‐mediated cytotoxicity and enhancement of lipid peroxidation.

The ‘housekeeping’ enzyme Cu/Zn‐superoxide dismutase (SOD‐1) is encoded by a gene residing on human chromosome 21, at the region 21q22 known to be involved in Down's syndrome. The SOD‐1 gene and the SOD‐1 cDNA were introduced into mouse L‐cells and human HeLa cells, respectively as part of recombinant plasmids containing the neoR selectable marker. Human and mouse transformants were obtained that expressed elevated levels (up to 6‐fold) of authentic, enzymatically active human SOD‐1. This enabled us to examine the consequences of hSOD‐1 gene dosage, apart from gene dosage effects contributed by other genes residing on chromosome 21. Human and mouse cell clones that overproduce the hSOD‐1 had altered properties; they were more resistant to paraquat than the parental cells and showed an increase in lipid peroxidation. The data are consistent with the possibility that gene dosage of hSOD‐1 contributes to some of the clinical symptoms associated with Down's syndrome.
Adenocarcinoma of glandular stomach and duodenum in Wistar rats ingesting N-methyl-N'-nitro-N-nitrosoguanidine, histopathology and associated secretory changes.

Summary N-Methyl-N′-nitro-N-nitrosoguanidine (NG) produces carcinoma of the glandular stomach and duodenum in rats when administered continuously in drinking water at a concentration of 83 mg/liter. The earliest histological changes consist of submucosal edema and basal mucosal fibrosis and were seen by the 3rd day on NG. By the 41st week on NG, 60% of rats develop tumors and by the 52nd week 80% of the animals had gastric adenocarcinoma, mostly in the antrum. Changes in gastric secretion were evaluated by the 4-hr pylorus ligation technique. Volume of gastric secretion and titratable acidity remained at control levels until late in the course of mucosal atrophy and cancer development. Pepsin secretion increased initially but gradually returned to control levels by the end of the year of NG exposure. Both the high frequency of tumor formation and the minimal toxicity of NG suggest that this carcinogen may be ideal for use in an experimental model studying gastric carcinogenesis.
Cocoa, Chocolate, and Cardiovascular Disease

A significant body of evidence demonstrates that diets rich in fruits and vegetables promote health and attenuate, or delay, the onset of various diseases, including cardiovascular disease, diabetes, certain cancers, and several other age-related degenerative disorders. The concept that moderate chocolate consumption could be part of a healthy diet has gained acceptance in past years based on the health benefits ascribed to selected cocoa components. Specifically, cocoa as a plant and chocolate as food contain a series of chemicals that can interact with cell and tissue components, providing protection against the development and amelioration of pathological conditions. The most relevant effects of cocoa and chocolate have been related to cardiovascular disease. The mechanisms behind these effects are still under investigation. However, the maintenance or restoration of vascular NO production and bioavailability and the antioxidant effects are the mechanisms most consistently supported by experimental data. This review will summarize the most recent research on the cardiovascular effects of cocoa flavanols and related compounds.
Endoscopic vein harvesting is influenced by patient-related risk factors and may be of specific benefit in female patients.

OBJECTIVES The standard of care regarding endoscopic vein harvesting (EVH) is still inhomogeneous across Europe. The current study aimed at elucidating patient-related factors favouring its application and procedure-related outcome in a tertiary care centre. METHODS All patients who underwent coronary artery bypass grafting with or without concomitant valve procedures between 2008 and 2011 were included. Emergency surgery and all arterial revascularization patients were excluded. RESULTS A total of 262 endoscopically harvested patients and 623 open vein harvested patients were included. Mortality, perfusion time and cross-clamp time were not significantly different. Peripheral artery disease predisposed open vein harvesting (odds ratio [OR] 1.9; P = 0.001); diabetes and a higher number of diseased coronary vessels favoured EVH (OR 0.6; P = 0.003 and 0.002). Further, the number of bypass grafts was significantly increased in the endoscopic group, but these patients required less periprocedural blood transfusions (1.4 ± 1.8 vs 1.8 ± 3.0; P = 0.035). Minor wound healing complications were more common in the open group (10.3 vs 3.8%; P = 0.001). Severe complications in the leg requiring surgical revision occured in 2.4% of open vein harvested patients compared with 1.1% for endoscopic patients (P = ns). After a multivariate regression analysis, only female gender remained as a significant risk factor for impaired wound healing (OR 2.4; P = 0.001), whereas EVH reduced the risk of wound-healing complications (OR 0.4; P = 0.008). CONCLUSIONS EVH dramatically reduced postoperative would healing complications. Women were more likely to develop mild and severe leg wound complications. Therefore, women may benefit even more from EVH. In general, the favourable outcomes of EVH should result in a more widespread use of this technology in men and women.
Clinical presentations and outcomes of influenza infection among hematology/oncology patients from a single cancer center: pandemic and post-pandemic seasons

Abstract Background: Influenza can cause severe infection in hematology/oncology patients. The occurrence of the 2009 pandemic represented an opportunity to study the impact of influenza on such patients in pandemic and post-pandemic seasons. Methods: We retrospectively reviewed medical records of hematology/oncology patients who had laboratory-confirmed influenza infection during the 2009 pandemic and the first post-pandemic seasons. We assessed influenza-related outcomes in both seasons with emphasis on the development of pneumonia and mortality. We also analyzed factors associated with poor outcomes. Results: We included 350 patients; 207 were diagnosed in the pandemic and 143 in the post-pandemic seasons. Influenza severity was similar in both seasons with no significant differences in the development of pneumonia or death. Infection with the pH1N1 virus was associated with the development of pneumonia (24.7% vs 14.9%, p = 0.029) but did not affect mortality. A multivariate analysis showed that initiation of antiviral treatment after > 48 h, healthcare acquisition of influenza, and low albumin were independent risk factors for the development of pneumonia (p values 0.022, 0.003, and < 0.0001, respectively). A log-rank test showed increased mortality in patients who received therapy > 48 h after onset of symptoms (p = 0.001). Conclusions: In hematology/oncology patients, influenza was as severe in the post-pandemic as in the pandemic season. Pneumonia developed more commonly in patients infected with pH1N1 virus. Healthcare acquisition of infection and low albumin were associated with the development of pneumonia. Delayed initiation of antiviral treatment was associated with both pneumonia and mortality.
Parasite‐induced surfacing in the cockle Austrovenus stuchburyi: adaptation or not?

Parasite manipulation of host behaviour is a compelling example of the extended phenotype. However, in many cases, such manipulation may be incorrectly assumed. Previous work has demonstrated that Austrovenus stuchburyi cockles stranded on mud‐flat surfaces due to an inability to re‐burrow both contain significantly more metacercariae of the trematode Curtuteria australis and are predated by the definitive host of this parasite at a faster rate than burrowed cockles. These results have been interpreted as strong evidence for a manipulation of cockle behaviour by the trematode to facilitate transmission to the definitive host. The model presented here, however, indicates that the selective advantage to the parasite of the altered host behaviour is currently of a negligible level at our study site that is highly unlikely to have been realized as an adaptation over evolutionary time. Hence, there are no grounds on which the more parsimonious explanation, that the altered host behaviour observed is simply an incidental side‐effect of infection, can be rejected. We thus maintain that for any change in the behaviour of infected hosts to be confirmed as potentially a parasite trait that has evolved in response to selection, the adaptive benefit taking into account the entire parasite life cycle may need to be considered.
Genetic Dissection of hTAFII130 Defines a Hydrophobic Surface Required for Interaction with Glutamine-rich Activators*

The general transcription factor TFIID is a multiprotein complex consisting of the TATA box-binding protein and multiple TATA box-binding protein-associated factors (TAFIIs). The central domain of human TAFII130 contains four glutamine-rich regions Q1-Q4 that interact with transcriptional activators such as Sp1 and CREB and mediate activation. We screened in yeast random point mutations introduced into Q1-Q4 against the Sp1 activation domain and obtained a distinct set of hTAFII130s with alterations in TAFII-activator interaction. Here we characterize functionally an hTAFII130 mutant containing a phenylalanine to serine change at position 311 (F311S) that is compromised in its ability to associate with Sp1B and CREB-N activation domains. Substitution of phenylalanine with tyrosine but not with isoleucine or tryptophan also reduced hTAFII130 interaction, suggesting that the hydrophobic character rather than the specific amino acid at this position is a key determinant of interaction. Deletion of nine amino acids (Δ9) surrounding Phe311 abolished the interaction of hTAFII130 with Sp1. Overexpression of hTAFII130Q1/Q2 and Q1-Q4 strongly inhibited Sp1-dependent transcriptional enhancement in transient transfection assays, whereas expression of either F311S or Δ9 only partially suppressed Sp1-mediated activation. Thus, a short hydrophobic sequence motif encompassing Phe311 in hTAFII130 represents a critical surface with which Sp1B interacts to activate transcription.
The role of laminins in basement membrane function

Laminins are a family of multifunctional macromolecules, ubiquitous in basement membranes, and represent the most abundant structural noncollagenous glycoproteins of these highly specialised extracellular matrices. Their discovery started with the difficult task of isolating molecules produced by cultivated cells or extracted from tissues. The development of molecular biology techniques has facilitated and accelerated the identification and the characterisation of new laminin variants making it feasible to identify full‐length polypeptides which have not been purified. Further, genetically engineered laminin fragments can be generated for studies of their structure‐function relationship, permitting the demonstration that laminins are involved in multiple interactions with themselves, with other components of the basal lamina, and with cells. It endows laminins with a central role in the formation, the architecture, and the stability of basement membranes. In addition, laminins may both separate and connect different tissues, i.e. the parenchymal and the interstitial connective tissues. Laminins also provide adjacent cells with a mechanical scaffold and biological information either directly by interacting with cell surface components, or indirectly by trapping growth factors. In doing so they trigger and control cellular functions. Recently, the structural and biological diversity of the laminins has started to be elucidated by gene targeting and by the identification of laminin defects in acquired or inherited human diseases. The consequent phenotypes highlight the pivotal role of laminins in determining heterogeneity in basement membrane functions.
Serum osteoprotegerin concentrations are decreased in women with the polycystic ovary syndrome.

OBJECTIVE Osteoprotegerin (OPG), an inhibitor of osteoclastic bone resorption, has a variety of functions including anti-inflammatory effects and a possible cardiovascular protective role. Both low-grade chronic inflammation and cardiovascular risk are increased in women with the polycystic ovary syndrome (PCOS). We aimed to study serum OPG concentrations in PCOS patients. DESIGN Case-control study including 40 PCOS patients matched with 40 non-hyperandrogenic women for age and body mass index. METHODS Basal serum sampling and standard oral glucose tolerance test, and measurement of serum OPG concentrations by commercial ELISA. RESULTS Serum OPG concentrations were lower in women with PCOS compared with those of controls (304+/-120 vs 363+/-105 pg/ml respectively; F=7.641, P=0.007) independently of obesity. No differences were observed in serum receptor activator of nuclear factor-kappaB ligand (RANKL) levels and in the RANKL/OPG molar ratio. A multivariate linear regression model (R(2)=0.208, F=6.579, P=0.001) showed that PCOS (beta=-0.281, P=0.008), obesity (beta=-0.245, P=0.022) and age (beta=0.296, P=0.006) were predictive of serum OPG concentrations. CONCLUSIONS Serum OPG concentrations are reduced in PCOS patients independently of obesity. Considering the anti-inflammatory effects of OPG, its reduced serum concentrations might contribute to the proinflammatory state and cardiovascular risk of PCOS patients.
Timing of prostaglandin exposure is critical for the inhibition of LPS‐ or IFN‐γ‐induced macrophage NO synthesis by PGE2

Macrophage nitric oxide (NO) synthesis is an integral component of the host defense system. We have previously found that NO and prostaglandins interact in a variety of ways. NO modulates Kupffer cell prostaglandin E2 (PGE2) production and we have recently described the inhibitory effects of PGE2 on NO synthesis in both Kupffer cells and hepatocytes. Activated macrophages produce a number of prostaglandins but studies regarding the capacity of prostaglandins to regulate macrophage NO synthesis have yielded conflicting results. We found that exogenous PGE2 decreased lipopolysaccharide (LPS)‐induced NO synthesis in murine resident peritoneal macrophages and in the RAW 264.7 murine macrophage cell line. PGE2 also suppressed NO synthesis in response to interferon‐γ (IFN‐γ) alone and a combination of LPS + IFN‐γ. Inhibition of endogenous PGE2 synthesis with indomethacin or ibuprofen had no effect on NO synthesis. PGE2 added with the activating stimulus was most effective. PGE2 lost the capacity to block NO synthesis if added more than 180 min after LPS. PGE2 decreased inducible NO synthase (iNOS) mRNA and immunoreactive iNOS protein, consistent with the hypothesis that exogenous PGE2 inhibits macrophage iNOS expression but that the inhibition depends on the time and concentration of prostaglandin exposure. J. Leukoc. Biol. 61: 712–720; 1997.
Assessing children's dental anxiety in New Zealand.

OBJECTIVES To investigate the reliability and validity of computerized anxiety assessment with New Zealand children, and to explore children's preferences for the method of anxiety assessment. DESIGN A validation study including test-retest reliability, and mean anxiety scores for items on the computerised Smiley Faces Program-Revised scale (SFP-R), together with qualitative data on children's preferences following two computer assessments and a pen-and-paper assessment using the Modified Children's Dental Anxiety Scale. PARTICIPANTS 206 children ranging in age from five to 13 years and from from three primary schools (one each of high, medium and low decile ranking). Approximately one-third (33%) were European, one-quarter M&ori or Polynesian, and 38% were Asian. RESULTS Estimates of internal consistency, (calculated using Cronbach's alpha), demonstrated an acceptable level of reliability for the SFP-R (alpha = 0.75). Test-retest data from the sub-sample of children across a two-week period showed a strong correlation (r = 0.75, p < 0.001). The SFP-R was found to significantly correlate with the MCDAS demonstrating concurrent validity (r = 0.67, p < 0.01). The mean anxiety score for all children was 19.9 (SD = 6.1). A two-way analysis of variance was employed to test for the effect of gender and age on total dental anxiety scores. There was no main effect for gender (F(1, 195) = 0.017, p > 0.05) or age group (F(3, 195) = 1.527, p > 0.05) and no interaction between the two factors. Children rated themselves most anxious when faced with the drill (mean = 4.5, SD = 1.7). 'Happy' faces were chosen some of the time for all of the items, even for the invasive procedures. CONCLUSIONS The SFP-R demonstrated good reliability and validity with New Zealand children and data indicated that it is a stable measure over time. It demonstrated concurrent validity, as evidenced by the moderately strong correlation with the MCDAS. Mean scores and frequency data suggest that, as there is still a significant proportion of children with very high overall anxiety scores, dental anxiety should be formally assessed and managed in NZ children. Children's preferences were for the computerised assessment of dental anxiety, supporting the continued development of Dental Jungle, the New Zealand dental anxiety intervention program.
Inhibition or Stimulation of Autophagy Affects Early Formation of Lipofuscin-Like Autofluorescence in the Retinal Pigment Epithelium Cell

The accumulation of lipofuscin in the retinal pigment epithelium (RPE) is dependent on the effectiveness of photoreceptor outer segment material degradation. This study explored the role of autophagy in the fate of RPE lipofuscin degradation. After seven days of feeding with either native or modified rod outer segments, ARPE-19 cells were treated with enhancers or inhibitors of autophagy and the autofluorescence was detected by fluorescence-activated cell sorting. Supplementation with different types of rod outer segments increased lipofuscin-like autofluorescence (LLAF) after the inhibition of autophagy, while the induction of autophagy (e.g., application of rapamycin) decreased LLAF. The effects of autophagy induction were further confirmed by Western blotting, which showed the conversion of LC3-I to LC3-II, and by immunofluorescence microscopy, which detected the lysosomal activity of the autophagy inducers. We also monitored LLAF after the application of several autophagy inhibitors by RNA-interference and confocal microscopy. The results showed that, in general, the inhibition of the autophagy-related proteins resulted in an increase in LLAF when cells were fed with rod outer segments, which further confirms the effect of autophagy in the fate of RPE lipofuscin degradation. These results emphasize the complex role of autophagy in modulating RPE autofluorescence and confirm the possibility of the pharmacological clearance of RPE lipofuscin by small molecules.