Miracle-dz/UniFAR-FTUs huggingface dataset:
Enamel matrix derivative protects human gingival fibroblasts from TNF‐induced apoptosis by inhibiting caspase activation

Emdogain®, a formulation of enamel matrix derivative (EMD), is used clinically for regeneration of the periodontium (tooth supporting tissues), but the molecular mechanisms of its action have not been elucidated. Several clinical studies suggested that EMD may also improve gingival healing after periodontal surgery and thus affect the fate of gingival fibroblasts (GFs). Since these cells are targets for local inflammatory mediators such as TNF, a pro‐apoptotic cytokine, during the course of periodontal disease, we tested whether EMD protects human GFs (hGFs) from TNF‐induced cytotoxicity. Quiescent primary hGFs were challenged with TNF (10–100 ng/ml) with or without EMD (100 µg/ml) pretreatment. Cell viability was assessed by neutral red staining, cell death by LDH release and apoptosis by caspase activity. Signaling pathways were evaluated by Western blotting and pharmacological inhibitors. TNF induced classical signs of apoptosis in hGFs, including typical cellular morphology and increased caspase activity. TNF‐induced cytotoxicity was entirely caspase‐dependent. Pretreatment (4–24 h) with EMD dramatically inhibited the activation of initiator and executioner caspases and enhanced hGF survival. Although TNF induced the activation of p38 MAPK, JNK, ERK and PI‐3K signaling, these pathways were not crucial for EMD protection of hGFs. However, EMD increased the levels of c‐FLIPL, an anti‐apoptotic protein located upstream of caspase activation. These data demonstrate, for the first time, that EMD protects hGFs from inflammatory cytokines and, together with our recent reports that EMD stimulates rat and human GF proliferation, could help explain the mechanisms whereby in vivo use of EMD promotes gingival healing. J. Cell. Physiol. 213:750–758. © 2007 Wiley‐Liss, Inc.
Neoliberal welfare reform and ‘rights’ compliance under Australian social security law

Recent neoliberal reforms to Australian social security and labour law privilege individual industrial bargaining and adopt a ‘job-first’ policy for welfare recipients, which exposes them to greater market pressures. This builds on earlier conservative Howard Government reforms, such as the privatisation of job matching services; insistence on mutual obligation and workfare expectations of social security clients; and intensification of loss of payment penalties for compliance breaches. This article examines the extent to which social security decision-making in Australia is favourably influenced by international treaties that include social security among the social and economic rights sought to be protected. It is argued that rights to social security are of their nature weak and sometimes internally conflicted, but this is compounded by their more limited purchase in Australian law. Consequently, international law has been of less assistance in protecting social security rights within Australia than is the case internationally. Everyone, as a member of society, has the right to social security and is entitled to realization… of the economic, social and cultural rights indispensable for… dignity and the free development of… personality. [Article 22, Universal Declaration of Human Rights, 10 December 1948. ]
Disordered interdomain region of Gins is important for functional tetramer formation to stimulate MCM helicase in Thermoplasma acidophilum

The eukaryotic MCM is activated by forming the CMG complex with Cdc45 and GINS to work as a replicative helicase. The eukaryotic GINS consists of four different proteins to form tetrameric complex. In contrast, the TaGins51 protein from the thermophilic archaeon, Thermoplasma acidophilum forms a homotetramer (TaGINS), and interacts with the cognate MCM (TaMCM) to stimulate the DNA-binding, ATPase, and helicase activities of TaMCM. All Gins proteins from Archaea and Eukarya contain α-helical A- and β-stranded B-domains. Here, we found that TaGins51 forms the tetramer without the B-domain. However, the A-domain without the linker region between the A- and B-domains could not form a stable tetramer, and furthermore, the A-domain by itself could not stimulate the TaMCM activity. These results suggest that the formation of the Gins51 tetramer is necessary for MCM activation, and the disordered linker region between the two domains is critical for the functional complex formation. Graphical Abstract The disordered linker region, but not the B-domain, of Thermoplasma acidophilum Gins51 (TaGins51) is critical for the tetramer formation, for its function to activate the replicative helicase (TaMCM).
Scanning Microscopy Scanning Microscopy X-Irradiation-Induced Disorganization of Cytoskeletal Filaments X-Irradiation-Induced Disorganization of Cytoskeletal Filaments and Cell Contacts in HT29 Cells and Cell Contacts in HT29 Cells

Organization of cytoskeleton and cell contacts were studied by immunochemistry and electron microscopy in confluent HT29 cultured cells following exposure to 0.5 and 1.0 Gy doses of X-ray. Microtubules were resistant to irradiation, whereas, the actin and intermediate fila ments disrupted rapidly following the treatment and their components appeared as clumps of actin and cytokeratin aggregates in the cytoplasm as demonstrated by immuno chemistry. Loss of cell contacts and decrease in the number of desmosomes was also characteristic of irradi ated cells. Electron microscopy revealed intact desmo somes in control cells and abnormal desmosomes in the irradiated samples characterized by the absence of tono filaments. The perinuclear filament network and cortical filaments were well detectable by electron microscopy. Under the effect of irradiation, the perinuclear filaments almost disappeared and, at the same time, small bundles of filaments were formed irregularly in the cytoplasm associated with amorphous material.
Effect of Transplant Center Volume on Cost and Readmissions in Medicare Lung Transplant Recipients.

RATIONALE Although lung transplant recipient survival is better at higher volume centers, the effect of center volume on admission cost and early hospital readmission is unknown. OBJECTIVES To understand the association between transplant center volume and recipient risk-adjusted transplant admission cost, in-hospital mortality, and early hospital readmission in lung transplant recipients. METHODS Medicare lung transplant recipients from May 4, 2005 to December 31, 2011 were identified through linkage of transplant registry and Medicare administrative claims. Transplant admission cost was extracted, adjusted for regional price variation, and compared across low-, intermediate-, and high-volume centers. A multivariable hierarchical generalized linear regression model was used to assess the effect of transplant center volume on recipient adjusted cost. Modified Poisson regression models were used to assess adjusted in-hospital mortality and early hospital readmission by transplant center volume. MEASUREMENTS AND MAIN RESULTS There were 3,128 Medicare lung transplant recipients identified. Unadjusted transplant cost was lower at high-volume centers (mean, $131,352 [SD, ±$106,165]; median, $90,177; interquartile range [IQR], $79,165-$137,915) than at intermediate-volume (mean, $138,792 [SD, ±$106,270]; median, $93,024; IQR, $82,700-$154,857) or low-volume (mean, $143,609 [SD, ±$123,316]; median, $95,234; IQR, $83,052-$152,149) centers (P < 0.0001). After adjusting for recipient health risk, low-volume centers had an 11.66% greater transplant admission cost (P = 0.040), a 41% greater risk for in-hospital mortality (P = 0.015), and a 14% greater risk for early hospital readmission (P = 0.033) compared with high-volume centers. There was no significant difference in transplant cost, in-hospital mortality, or early hospital readmission between intermediate- and high-volume centers. CONCLUSIONS Lung transplant admission cost, in-hospital mortality, and early hospital readmission rate are lower at high-volume centers compared with low-volume centers.
Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: A systematic review

The accurate identification of peripheral artery disease (PAD) in patients with diabetes and foot ulceration is important, in order to inform timely management and to plan intervention including revascularisation. A variety of non‐invasive tests are available to diagnose PAD at the bedside, but there is no consensus as to the most useful test, or the accuracy of these bedside investigations when compared to reference imaging tests such as magnetic resonance angiography, computed tomography angiography, digital subtraction angiography or colour duplex ultrasound. Members of the International Working Group of the Diabetic Foot updated our previous systematic review, to include all eligible studies published between 1980 and 2018. Some 15 380 titles were screened, resulting in 15 eligible studies (comprising 1563 patients, of which >80% in each study had diabetes) that evaluated an index bedside test for PAD against a reference imaging test. The primary endpoints were positive likelihood ratio (PLR) and negative likelihood ratio (NLR). We found that the most commonly evaluated test parameter was ankle brachial index (ABI) <0.9, which may be useful to suggest the presence of PAD (PLR 6.5) but an ABI value between 0.9 and 1.3 does not rule out PAD (NLR 0.31). A toe brachial index >0.75 makes the diagnosis of PAD less likely (NLR 0.14‐0.24), whereas pulse oximetry may be used to suggest the presence of PAD (if toe saturation < 2% lower than finger saturation; PLR 17.23‐30) or render PAD less likely (NLR 0.2‐0.27). We found that the presence of triphasic tibial waveforms has the best performance value for excluding a diagnosis of PAD (NLR 0.09‐0.28), but was evaluated in only two studies. In addition, we found that beside clinical examination (including palpation of foot pulses) cannot reliably exclude PAD (NLR 0.75), as evaluated in one study. Overall, the quality of data is generally poor and there is insufficient evidence to recommend one bedside test over another. While there have been six additional publications in the last 4 years that met our inclusion criteria, more robust evidence is required to achieve consensus on the most useful non‐invasive bedside test to diagnose PAD.
Glycemic Thresholds for Spontaneous Abortion and Congenital Malformations in Insulin‐Dependent Diabetes Mellitus

Objective: To test the hypothesis that women with insulin-dependent (type I) diabetes have a threshold of glycemic control in early pregnancy for increased risks of spontaneous abortion and congenital malformations. Methods: Receiver-operating characteristic (ROC) curves were formed for the occurrence of abortion and malformations as a function of the median first-trimester preprandial blood glucose concentration and the first measured glycohemoglobin concentration in pregnant women with type I diabetes. Results: Fifty-two of the 215 women (24%) who enrolled before 9 weeks' gestation had spontaneous abortions. Six percent of the women enrolled before 14 weeks had infants with major congenital malformations. Thresholds for an increased risk of abortion and malformations were a median first-trimester blood glucose concentration of 120–130 mg/dL or an initial glycohemoglobin concentration of 12–13% (6.2–7.5 standard deviations above the normal mean). Conclusions: Type I diabetic women with initial glycohemoglobin concentrations in pregnancy above 12% or median first-trimester preprandial glucose concentrations above 120 mg/dL have an increased risk of abortion and malformations. Below these glycemic thresholds, the risks are comparable to those in nondiabetic women.
Identification of an RNA-dependent RNA polymerase in Drosophila involved in RNAi and transposon suppression

Here, we show that recombinant Drosophila elp1 (D-elp1) produced in Sf9 cells or Escherichia coli, corresponding to the largest of the three subunits in the RNA polymerase II core elongator complex, has RNA-dependent RNA polymerase (RdRP) activity. D-elp1 is a noncanonical RdRP that can synthesize dsRNA from different ssRNA templates using either a primer-dependent or primer-independent initiation mechanism. Of the three core subunits, only D-elp1 depletion inhibits RNAi in S2 cells but does not affect micro RNA function. Furthermore, D-elp1 depletion results in increased steady state levels of representative transposon RNAs and a decrease in the corresponding transposon antisense transcripts and endo siRNAs. In contrast, although Dcr-2 depletion results in increased transposon RNA levels and a reduction in the corresponding endo siRNAs, there is no change in the transposon antisense RNA levels. In D-elp1 null third instar larvae transposon RNA levels are also increased and the corresponding transposon antisense RNAs are reduced. D-elp1 associates tightly with Dcr-2, similar to the Dicer-RdRP interaction observed in lower eukaryotes. These results identify an aspect of the RNAi pathway in Drosophila that suggest transposon derived endo siRNAs, critical for transposon suppression, are produced, in part, in a D-elp1 dependent step that converts transposon RNA into dsRNA that is subsequently processed by Dcr-2. The generality of this mechanism in genome defense and RNA silencing in higher eukaryotes is suggested.
Carbonic anhydrase II mRNA expression in individual osteoclasts under “resorbing” and “nonresorbing” conditions

Rabbit osteoclasts can be transformed from a nonresorbing state to a resorbing state by transferring them from culture medium at pH 7.5 to one at pH 6.5. We evaluated whether expression of mRNA for carbonic anhydrase (CA‐II) could be used as an indicator of the state of activity of individual osteoclasts. A cDNA probe to rabbit carbonic anhydrase II (CA‐II) was prepared and used for in situ hybridization analysis of osteoclasts isolated from neonatal rabbit long bones. Quantitation by grain counting revealed heterogeneity within the osteoclast population: osteoclasts with a “compact” (rounded, less spread) morphology expressed higher levels of CA‐II mRNA than “spread” osteoclasts with similar numbers of nuclei. When maintained at pH 6.5 for 6 h, the level of CA‐II mRNA was increased significantly in osteoclasts of both morphologies compared with those in parallel cultures maintained at pH 7.5. These results were confirmed by quantitating CA‐II mRNA using the polymerase chain reaction (PCR). Oligonucleotide primers specific for rabbit CA‐II were synthesized and used to amplify CA‐II cDNA transcribed from mRNA prepared from single or small numbers (one to eight cells) of osteoclasts that were collected with a micromanipulator. This generated a ∼510 bp PCR product, corresponding to the predicted size of the CA‐II fragment encompassed by the primers. For quantitation, CA‐II mRNA levels were compared with the levels of a ∼900 bp actin fragment that was coamplified in the same reaction mixture or amplified separately in a duplicate sample of the reaction mixture. The ratio of CA‐II mRNA expression to actin mRNA expression was significantly increased in osteoclasts cultured at pH 6.5 for 6 h compared with osteoclasts maintained at pH 7.5 (1.89 + 0.12 versus 0.98 + 0.06, n = 39, mean + SEM, of all assays combined; P < 0.001). Our results demonstrate that CA‐II mRNA expression is upregulated in osteoclasts in the resorptive state. The methods used provide a novel molecular approach for analyzing osteoclast activity with assays that are applicable to single cells and obviate the problem of osteoclast impurity, allowing investigation of osteoclast heterogeneity.
Iron status in patients with pyruvate kinase deficiency: neonatal hyperferritinaemia associated with a novel frameshift deletion in the PKLR gene (p.Arg518fs), and low hepcidin to ferritin ratios

Pyruvate kinase (PK) deficiency is an iron‐loading anaemia characterized by chronic haemolysis, ineffective erythropoiesis and a requirement for blood transfusion in most cases. We studied 11 patients from 10 unrelated families and found nine different disease‐causing PKLR mutations. Two of these mutations ‐ the point mutation c.878A>T (p.Asp293Val) and the frameshift deletion c.1553delG (p.(Arg518Leufs*12)) ‐ have not been previously described in the literature. This frameshift deletion was associated with an unusually severe phenotype involving neonatal hyperferritinaemia that is not typical of PK deficiency. No disease‐causing mutations in genes associated with haemochromatosis could be found. Inappropriately low levels of hepcidin with respect to iron loading were detected in all PK‐deficient patients with increased ferritin, confirming the predominant effect of accelerated erythropoiesis on hepcidin production. Although the levels of a putative hepcidin suppressor, growth differentiation factor‐15, were increased in PK‐deficient patients, no negative correlation with hepcidin was found. This result indicates the existence of another as‐yet unidentified erythroid regulator of hepcidin synthesis in PK deficiency.
Self-reported mental health status and recent mammography screening.

OBJECTIVE The purpose of this study was to assess the association between self-perceived mental health status and mammography screening in Kentucky. METHODS Using a cross-sectional design, we examined survey data from the 2002 Kentucky Behavioral Risk Factor Surveillance System (BRFSS) for women aged > or =40. Mental health status was measured by the reported number of days that mental health was not good; the number of days feeling sad, blue, or depressed; and the number of days feeling worried, tense, or anxious. The outcome was mammography within the last 2 years. Three logistic regression analyses were performed, one with each of the mental health status questions as the predictor variable. Analyses controlled for age, race, marital status, education, income, and health insurance status. RESULTS The numbers of poor mental health days, depressed days, and anxious days were found to be significant or near-significant predictors of recent mammography. Odds ratios (ORs) comparing women reporting 30 poor mental health days, depressed days, or anxious days with similar women reporting zero days were estimated to be 1.68 (95% confidence interval [CI] 1.08-2.63), 1.49 (0.93-2.40), and 1.46 (0.96-2.23), respectively. CONCLUSIONS Self-reported poor mental health, depression, and anxiety may be associated with nonreceipt of regular mammography screening. How mental health symptoms and self-reported poor mental health status contribute to decreased mammography screening should be explored.
Yeast SNF1 protein kinase interacts with SIP4, a C6 zinc cluster transcriptional activator: a new role for SNF1 in the glucose response

The SNF1 protein kinase has been widely conserved in plants and mammals. In Saccharomyces cerevisiae, SNF1 is essential for expression of glucose-repressed genes in response to glucose deprivation. Previous studies supported a role for SNF1 in relieving transcriptional repression. Here, we report evidence that SNF1 modulates function of a transcriptional activator, SIP4, which was identified in a two-hybrid screen for interaction with SNF1. The N terminus of the predicted 96-kDa SIP4 protein is homologous to the DNA-binding domain of the GAL4 family of transcriptional activators, with a C6 zinc cluster adjacent to a coiled-coil motif The C terminus contains a leucine zipper motif and an acidic region. When bound to DNA, a LexA-SIP4 fusion activates transcription of a reporter gene. Transcriptional activation by SIP4 is regulated by glucose and depends on the SNF1 protein kinase. Moreover, SIP4 is differentially phosphorylated in response to glucose availability, and phosphorylation requires SNF1. These findings suggest that the SNF1 kinase interacts with a transcriptional activator to modulate its activity and provide the first direct evidence for a role of SNF1 in activating transcription in response to glucose limitation.
Effectiveness of delayed activated charcoal administration in simulated paracetamol (acetaminophen) overdose.

AIMS Oral activated charcoal is used to treat drug overdose and is effective at reducing drug absorption when administered within 1 h of drug ingestion. There are fewer data on efficacy when the delay is longer, as is the case in most drug overdoses. This study investigated the efficacy of activated charcoal at preventing paracetamol (acetaminophen) absorption after simulated overdose when administration was delayed between 1 and 4 h. METHODS An open randomized-order four-way crossover study was performed in healthy volunteers comparing the effect of activated charcoal 50 g on the absorption of 3 g paracetamol tablets when administered after an interval of 1, 2 or 4 h or not at all. Plasma paracetamol concentrations were measured over 9 h after paracetamol ingestion using h.p.l.c. and areas under the curve between 4 and 9 h (AUC(4,9 h)) calculated as a measure of paracetamol absorption. RESULTS Activated charcoal significantly reduced paracetamol AUC(4,9 h) when administered after 1 h (mean reduction 56%; 95% Confidence intervals 34, 78; P<0.002) or 2 h (22%; 6, 39; P<0.03) but not after 4 h (8%; -8, 24). When administered after 1 h activated charcoal reduced individual plasma paracetamol concentrations significantly at all times between 4 and 9 h after paracetamol administration. Administration at 2 or 4 h had no significant effect. CONCLUSIONS These results in healthy volunteers cannot be extrapolated directly to poisoned patients. However, they provide no evidence of efficacy for activated charcoal when administered after an interval of more than 2 h.
Detection of Helicobacter pylori and Chlamydia pneumoniae DNA in human coronary arteries and evaluation of the results with serologic evidence of inflammation.

OBJECTIVE Atherosclerosis is pathologically similar to a chronic inflammatory response. Recent reports have suggested that Chlamydia pneumoniae (C. pneumoniae) and Helicobacter pylori (H. pylori) play a role in the pathogenesis of atherosclerosis but this relation has not been confirmed on an inflammatory background. METHODS Twenty-nine consecutive patients admitted to Suleyman Demirel University Medical School Cardiovascular Surgery Department, Isparta, Turkey between May 2002 to June 2003 were included in the study and the presence of C. pneumoniae and H. pylori DNA in atherosclerotic plaques of 14 coronary endarterectomy specimens and 15 left internal mammarian artery (LIMA) specimens as control subjects were determined by polymerase chain reaction. Serologic evidence of infection and inflammatory markers were also determined in both groups. RESULTS Two C. pneumoniae DNA cases from the plaque group (14.3%) and 4 H. pylori DNA cases; 3 from plaque (21.4%) and one from the LIMA groups (6.7%) were detected. The C-reactive protein (mg/L) were higher in DNA positive samples of C. pneumoniae (66.58) and H. pylori (21.93) compared to DNA negatives of C. pneumoniae (8.49) and H. pylori (10.98), similarly interleukin-6 (U/L) levels were higher in DNA positive samples of C. pneumoniae (42.25) and H. pylori (56.37) compared with DNA negatives of C. pneumoniae (17.52) and H. pylori (13.28), but the differences were not statistically significant. Apolipoprotein B levels were significantly higher in C. pneumoniae immunoglobulin M positive cases (0.844 g/L) compared with negatives (0.661 g/L) (p=0.004). CONCLUSION Chronic infections modify the serum lipid profile in a way that increases the risk of atherosclerosis. The increased titers of inflammation markers in DNA positive patients support inflammation in atherosclerosis, however, the results should be reproduced in a larger cohort.