Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Antigen R-mediated mRNA Stabilization Is Required for Ultraviolet B-induced Autoinduction of Amphiregulin in Keratinocytes*

Background: Amphiregulin (AREG) is a ligand for the EGF receptor (EGFR) and autoinduces its own expression. Results: Human antigen R (HuR), an mRNA-binding protein, stabilizes AREG mRNA in ultraviolet B (UVB)-exposed keratinocytes. Conclusion: HuR is a key regulator for UVB-mediated autoinduction of AREG expression. Significance: Clarifying the mechanisms underlying the production of EGF family members is crucial for understanding cancers caused by aberrant EGFR signaling. All members of the EGF family are produced as transmembrane precursors that are proteolytically processed into soluble forms by disintegrin and metalloproteinases (ADAMs) for autocrine/paracrine pathways. In turn, the ligand-activated EGF receptor (EGFR) induces the expression of EGF family members, so-called “autoinduction. ” However, it is not well understood how this autoinduction occurs. In this study, we investigated the molecular mechanism of the autoinduction of amphiregulin (AREG), a member of the EGF family. We found that ultraviolet B (UVB) exposure increased the AREG mRNA level by stabilization of its mRNA in a human immortalized keratinocyte cell line, HaCaT. The 3′ UTR of AREG mRNA was responsible for binding to an mRNA-binding protein, human antigen R (HuR), and the interaction between AREG mRNA and HuR was enhanced by UVB. Inducible knockdown of HuR expression significantly decreased AREG mRNA stability. Interestingly, treatment of HaCaT cells with an EGFR inhibitor, an EGFR neutralizing antibody, or an ADAM inhibitor destabilized AREG mRNA. In the case of ADAM inhibition, administration of soluble AREG restored the mRNA level, indicating that the stabilization occurs in a shedding-dependent manner of EGFR ligands. The HuR dependence of AREG mRNA and protein expression was also confirmed in human primary keratinocytes. Taken together, we propose a novel mechanism by which HuR regulates the stability of AREG mRNA in keratinocytes after UVB exposure and suggest that targeting of HuR functions might be crucial for understanding skin cancers caused by aberrant EGF family member-EGFR signaling.
Analysis of upstream elements in the HuC promoter leads to the establishment of transgenic zebrafish with fluorescent neurons.

HuC encodes an RNA binding protein homologous to Drosophila elav that serves as an excellent early marker for differentiating neurons. We have characterized the promoter of the zebrafish HuC gene by examining the ability of 5'-upstream fragments to drive expression of green fluorescent protein (GFP) in live embryos. We determined that 2.8 kb of the 5'-flanking sequence is sufficient to restrict GFP gene expression to neurons. The core promoter spans 251 base pairs and contains a CCAAT box and one SP1 sequence but no TATA box is present near the transcription start site. A putative MyT1 binding site and at least 17 E-box sequences are necessary to maintain the neuronal specificity of HuC expression. Interestingly, sequential removal of the putative MyT1 binding site and 14 distal E boxes does not appear to abolish neuronal expression; rather, it leads to a progressive expansion of GFP expression into muscle cells. Further removal of the three proximal E boxes eliminates neuronal and muscle specificity of GFP expression and leads to ubiquitous expression of GFP in the whole body. Identification of key components of the HuC promoter has led to the establishment of a stable zebrafish transgenic line (HuC-GFP) in which GFP is expressed specifically in neurons. We crossed mind bomb (mib) fish with this line to visualize their neurogenic phenotype in live mib(-/-) mutant embryos. This cross illustrates how HuC-GFP fish could be used in the future to identify and analyze zebrafish mutants with an aberrant pattern of early neurons.
Predicting the appropriate use of carotid endarterectomy, upper gastrointestinal endoscopy, and coronary angiography.

BACKGROUND AND METHODS In a nationally representative population 65 years of age or older, we have demonstrated that about one quarter of coronary angiographies and upper gastrointestinal endoscopies and two thirds of carotid endarterectomies were performed for reasons that were less than medically appropriate. In this paper we examine whether specific characteristics of patients (age, sex, and race), physicians (age, board-certification status, and experience with the procedure), or hospitals (teaching status, profit-making status, and size) predict whether a procedure will be performed appropriately. RESULTS In general, we found that little of the variability in the appropriateness of care (4 percent or less) could be explained on the basis of standard, easily obtainable data about the patient, the physician, or the hospital. For all three procedures, however, performance in a teaching hospital increased the likelihood that the reasons would be medically appropriate (P = 0.09 for angiography, P = 0.30 for endoscopy, and P less than 0.01 for endarterectomy). In addition, angiographies were more often performed for appropriate reasons in older or more affluent patients (P less than 0.01 for both). Being treated by a surgeon who performed a high rather than a low number of procedures decreased the likelihood of an appropriate endarterectomy by one third, from 40 to 28 percent (P less than 0.01). CONCLUSIONS Appropriateness of care cannot be closely predicted from many easily determined characteristics of patients, physicians, or hospitals. Thus, for the present, if appropriateness is to be improved it will have to be assessed directly at the level of each patient, hospital, and physician.
Asbestos exposure and laryngeal cancer.

OBJECTIVE To carry out a systematic review of the evidence relating asbestos exposure to the risk of laryngeal cancer. METHOD All identified studies of asbestos workers providing data on laryngeal disease were reviewed, together with studies of laryngeal cancers giving epidemiological or experimental evidence of associated exposures. RESULTS Confounding due to smoking and alcohol intake, and to a lesser extent diet and socio-economic factors, creates a major difficulty over the identification of any asbestos or other occupational effect. Not only are smoking and alcohol independently associated with large increases in relative risk (RR) of laryngeal cancer, but also have a synergistic effect with each other. Few of the studies provide details of either habit. Among 24 prospective studies for which a standardized mortality ratio (SMR) was available, nine had an SMR at or below unity, and among a further 11 without an SMR for comparison, in only one was there a clear excess risk. In 17 retrospective studies, only two showed a significantly increased RR. Evidence from animal experiments, studies of associations with pleural plaques, and autopsy findings also appear negative or inconclusive. CONCLUSION The evidence does not indicate that asbestos exposure increases the RR of laryngeal cancer.
[Umbilical cord complications in twin pregnancies].

OBJECTIVES The postpartum umbilical cord examination can provide a lot of significant information concerning discordant twin growth or reasons of intrauterine death of one or all the fetuses. The aim of this study was the postpartum assessment of umbilical cords in twin pregnancies. MATERIAL AND METHODS The examination material consisted placentas coming from 110 twin pregnancies. The analysis concerned the assessment of placenta types, the umbilical cords attachment place and also the twins birth weight. RESULTS Basing on the studies of placentas coming from 110 twin pregnancies 76 (69.0%) dichorionic and 34 (31.0%) monochorionic placentas were found. Among dichorionic, 40 (53%) separated and 36 (47%) fused placentas were observed. Among monochorionic 31 (91%) diamniotic and 3 (9.0%) monoamniotic placentas were present. Abnormal umbilical insertion to placenta was most frequently observed in monochorionic pregnancies: in diamniotic--marginal insertion in 21.2%, velamentous insertion in 15.9%, and in monoamniotic--equally 33.3%. In dichorionic pregnancies, for fused placentas--marginal in 8.7%, velamentous in 9.1%, and for separated--5.6% and 3.1%. CONCLUSIONS The abnormal umbilical cord insertions to the placenta was most frequently found in monochorionic pregnancies. Among pairs of twin born with body weight discordance, the abnormal umbilical cord insertion was more frequently found in the case of the smaller newborn.
Comparison of dorzolamide and acetazolamide as suppressors of aqueous humor flow in humans.

OBJECTIVE To compare the efficacy of topical 2% dorzolamide hydrochloride (Trusopt) as a suppressor of aqueous humor flow in the human eye with the efficacy of systemically administered acetazolamide (Diamox). DESIGN A randomized, double-masked, placebo-controlled study of 40 human subjects in 2 academic centers. The effect of dorzolamide on aqueous humor flow was compared with that of acetazolamide as measured by the rate of clearance of topically applied fluorescein. RESULTS Acetazolamide reduced aqueous flow from 3.18 +/- 0.70 (mean +/- SD) to 2.23 +/- 0.48 microL per minute, a reduction of 30% (P < .001), and dorzolamide reduced the flow to 2.65 +/- 0.64 microL per minute, a reduction of 17% (P < .001). The difference between the effect of acetazolamine and dorzolamide was significant (P < .001). When acetazolamide is added to dorzolamide, the aqueous flow was reduced further to 2.21 +/- 0.47 microL per minute, an additional reduction of 16% (P < .001). When dorzolamide was added to acetazolamide, no additional reduction was observed (P = .73). Similar effects were observed for intraocular pressure. Acetazolamide reduced pressure from 12.5 +/- 2.2 (mean +/- SD) to 10.1 +/- 2.2 mm Hg, a decrease of 19% (P < .001) and dorzolamide reduced it to 10.8 +/- 2.1 mm Hg, or a decrease of 13% (P < .001). The greater effect of acetazolamide than dorzolamide was significant (P = .03). CONCLUSIONS For reasons that are not known, the topically applied carbonic anhydrase inhibitor 2% dorzolamide hydrochloride is not as effective as systemically administered acetazolamide. Clinicians who prescribe dorzolamide should expect less of an ocular hypotensive effect than that experienced from systemically administered acetazolamide.
7-Hydroperoxycholesterol as a marker of oxidative stress in rat kidney induced by paraquat

The in vivo paraquat-induced oxidative stress in rat tissue was studied by analyzing cholesterol-derived hydroperoxide as an index of lipid peroxidation. Paraquat (10 mg/kg) was administered i.p. to rats. Rats were sacrificed and lung, liver, and kidney were collected 2, 24 h, and 5 d after paraquat injection. Lipids were extracted and analyzed by HPLC with post-column chemiluminescence. We found that two cholesterol-derived hydroperoxides, 7α-hydroperoxycholest-5-en-3β-ol (7α-OOH) and 7β-hydroperoxycholest-5-en-3β-ol (7β-OOH) were present in lungs of control animals (0.06 and 0.06 nmol/g, respectively), in livers (6.5 and 15.8 nmol/g, respectively) and in kidneys (3.7 and 8.9 nmol/g, respectively). In liver paraquat increased lipid peroxidation approximately by 60% over the levels of control animals only at 2 h after paraquat treatment. In kidney, augmented lipid peroxidation, 7α-OOH and 7β-OOH (by 70% and 147%, respectively) above levels was found at 2 h after paraquat treatment. Interestingly, these increase remained in kidney of rats 5 d after a single dose of paraquat. In contrast, cholesterol-derived hydroperoxides were not affected in lung of paraquat dosed rats. This is the first report on 7α-OOH and 7β-OOH accumulations in rat liver and kidney, and it seems to reflect greater oxidative stress in the pathology of kidney of rats treated with acute paraquat at low dose.
Host–microbe interactions that shape the pathogenesis of Acinetobacter baumannii infection

Acinetobacter baumannii is an opportunistic pathogen that has emerged as a prevalent source of nosocomial infections, most frequently causing ventilator‐associated pneumonia. The emergence of pan‐drug resistant strains magnifies the problem by reducing viable treatment options and effectively increasing the mortality rate associated with Acinetobacter infections. In light of this rising threat, research on A. baumannii epidemiology, antibiotic resistance, and pathogenesis is accelerating. The recent development of both in vitro and in vivo models has enabled studies probing the host–Acinetobacter interface. Bacterial genetic screens and comparative genomic studies have led to the identification of several A. baumannii virulence factors. Additionally, investigations into host defence mechanisms using animal models or cell culture have provided insight into the innate immune response to infection. This review highlights some of the key attributes of A. baumannii virulence with an emphasis on bacterial interactions with the innate immune system.
Influence of Genotype and Haplotype of MDR1 (C3435T, G2677A/T, C1236T) on the Incidence of Breast Cancer--a Case-Control Study in Jordan.

BACKGROUND Breast cancer is the leading cause of cancer death among women and the second in humans worldwide. Many published studies have suggested an association between MDR1 polymorphisms and breast cancer risk. Our aim was to study the association between genetic polymorphism of MDR1 at three sites (C3435T, G2677A/T, and C1236T) and their haplotype and the risk of breast cancer in Jordanian females. MATERIALS AND METHODS A case-control study involving 150 breast cancer cases and 150 controls was conducted. Controls were age-matched to cases. The polymerase chain reaction/restriction fragment length polymorphism (PCR- RFLP) technique and sequencing were performed to analyse genotypes. RESULTS The distribution of MDR1 C3435T genotypes differed between cases and controls [cases, CC 45.3%, CT 41.3%, and TT 13.3%; controls, CC 13.4%, CT 43.3%, and TT 30.2%, p < 0.001]. Similarly, the distribution of G2677A/T significantly differed [cases, GG 43.1 %, GT+GA 50.9% and AA+TT 6%; controls, GG 29.6 %, GT+GA 50.9%, and AA+TT 19.4%, p = 0.004]. On the other hand, genotype and allelotype distribution of C1236T was not statistically different between cases and controls (p=0.56 and 0.26, respectively). The CGC haplotype increased the risk to breast cancer by 2.5-fold compared to others, while TGC and TTC haplotypes carried 2.5- and 5-fold lower risk of breast cancer, respectively. CONCLUSIONS Genetic polymorphisms of MDR1 C3435T and G2677A/T, but not C1236T, are associated with increased risk of breast cancer. In addition, CGC, TGC and TTC haplotypes have different impacts on the risk of breast cancer. Future, larger studies are needed to validate these findings.
Eye masks and earplugs improve patient's perception of sleep.

BACKGROUND Critical care patients experience deranged sleep for a number of reasons including noise, environment, severity of illness and care activities. This service evaluation was prompted by the concern that patients were not getting enough sleep because of excessive noise levels in our unit. AIM To determine self-reported sleep experiences and perceived factors affecting sleep quality among intensive care patients before and after the introduction of earplugs and eye masks. DESIGN A pre/post intervention service evaluation (n = 100) was completed to evaluate the efficacy of eye masks and earplugs in critical care patients. METHODS Participants (n = 100) were recruited from one large critical care unit. During August 2008 to January 2009, 50 patients were recruited and received standard care. A further 50 were recruited between May and October 2009. This group was given eye masks and earplugs to aid their sleep on the critical care unit. A data collection tool was devised comprising three elements: (1) collection of demographic data from hospital charts and medical notes, (2) rating quality and quantity of sleep using two likert scales and (3) a four-item data collection sheet was used comprising of one closed and three open-ended questions. RESULTS Noise was identified as a significant factor preventing sleep in the pre-intervention (50%) and intervention (52%) group. The pre-intervention group identified medication (26%) (i.e. night sedation or analgesia) and 'simply nothing' (24%) as factors promoting sleep. CONCLUSION The intervention group identified earplugs (22%) and eye masks (28%) as factors promoting sleep. It appears that simple interventions such as eye masks and earplugs may be a valuable addition to patients attempting to sleep in a critical care unit. RELEVANCE TO CLINICAL PRACTICE Earplugs and eye masks are a useful adjunct to strategies promoting sleep in critical care areas.
"Cognitive Impairment Associated with Toxigenic Fungal Exposure": A Critique and Critical Analysis

Recently Gordon et al. (2004) reported the results of a study relating exposure to toxigenic fungi to cognitive impairment. A number of methodological problems limit the utility of this study, including the authors' not examining a number of potential confounding variables, use of a mild traumatic brain injury group as a comparison, and problematic statistical analyses increasing the Type 1 error rate. Based on these limitations, the authors' conclusion that mold-exposed people have more cognitive and physical symptoms than normal controls is questionable at best. This critique describes some of the problems with the methodology employed and the related difficulty in drawing conclusions from their work.
Imaging of Cell Proliferation: Status and Prospects

Increased cellular proliferation is an integral part of the cancer phenotype. Several in vitro assays have been developed to measure the rate of tumor growth, but these require biopsies, which are particularly difficult to obtain over time and in different areas of the body in patients with multiple metastatic lesions. Most of the effort to develop imaging methods to noninvasively measure the rate of tumor cell proliferation has focused on the use of PET in conjunction with tracers for the thymidine salvage pathway of DNA synthesis, because thymidine contains the only pyrimidine or purine base that is unique to DNA. Imaging with 11C-thymidine has been tested for detecting tumors and tracking their response to therapy in animals and patients. Its major limitations are the short half-life of 11C and the rapid catabolism of thymidine after injection. These limitations led to the development of analogs that are resistant to degradation and can be labeled with radionuclides more conducive to routine clinical use, such as 18F. At this point, the thymidine analogs that have been studied the most are 3′-deoxy-3′-fluorothymidine (FLT) and 1-(2′-deoxy-2′-fluoro-1-β-d-arabinofuranosyl)-thymine (FMAU). Both are resistant to degradation and track the DNA synthesis pathway. FLT is phosphorylated by thymidine kinase 1, thus being retained in proliferating cells. It is incorporated by the normal proliferating marrow and is glucuronidated in the liver. FMAU can be incorporated into DNA after phosphorylation but shows less marrow uptake. It shows high uptake in the normal heart, kidneys, and liver, in part because of the role of mitochondrial thymidine kinase 2. Early clinical data for 18F-FLT demonstrated that its uptake correlates well with in vitro measures of proliferation. Although 18F-FLT can be used to detect tumors, its tumor-to-normal tissue contrast is generally lower than that of 18F-FDG in most cancers outside the brain. The most promising use for thymidine and its analogs is in monitoring tumor treatment response, as demonstrated in animal studies and pilot human trials. Further work is needed to determine the optimal tracer(s) and timing of imaging after treatment.
Dermatitis herpetiformis in a treated coeliac child.

demonstrated at myoneural junctions. Though proteins of this size can be transmitted to the fetus intact, the process is usually selective. However, absorption of tenanus toxin by the fetus from the uterine lumen has been shown in some species, and direct infection of the fetus, though almost certainly incompatible with fetal survival, cannot be entirely excluded. Nevertheless, it is unlikely that a toxin of this physiological specificity, even if it reached the fetus, would have any effects additional to those seen in the adult. There are several published reports of pregnancies surviving maternal tetanus in one of which the tetanus occurred at the end of the first trimester and in no case did an abnormal fetus result.
Cell cycle kinetics of expanding populations of neural stem and progenitor cells in vitro

Neural stem cells (NSCs) are undifferentiated, primitive cells with important potential applications including the replacement of neural tissue lost due to neurodegenerative diseases, including Parkinson's disease, as well as brain and spinal cord injuries, including stroke. We have developed methods to rapidly expand populations of mammalian stem and progenitor cells in neurosphere cultures. In the present study, flow cytometry was used in order to understand cell cycle activation and proliferation of neural stem and progenitor cells in suspension bioreactors. First, a protocol was developed to analyze the cell cycle kinetics of NSCs. As expected, neurosphere cells were found to cycle slowly, with a very small proportion of the cell population undergoing mitosis at any time. Large fractions (65–70%) of the cells were detected in G1, even in rapidly proliferating cultures, and significant fractions (20%) of the cells were in G0. Second, it was observed that different culturing methods influence both the proportion of neurosphere cells in each phase of the cell cycle and the fraction of actively proliferating cells. The results show that suspension culture does not significantly alter the cell cycle progression of neurosphere cells, while long‐term culture (>60 days) results in significant changes in cell cycle kinetics. This suggests that when developing a process to produce neural stem cells for clinical applications, it is imperative to track the cell cycle kinetics, and that a short‐term suspension bioreactor process can be used to successfully expand neurosphere cells. © 2004 Wiley Periodicals, Inc.
GIANTS AMONG MICROMORPHS: WERE CINCINNATIAN (ORDOVICIAN, KATIAN) SMALL SHELLY PHOSPHATIC FAUNAS DWARFED?

Abstract Small fossils are preserved as phosphatic (carbonate fluorapatite) micro-steinkerns (~ 0.5 mm diameter) in Upper Ordovician beds of the Cincinnati area. Mollusks are common, along with bryozoan zooecia, echinoderm ossicles, and other taxa. Similar occurrences of Ordovician micromorphic mollusks have been interpreted as ecologically dwarfed and adapted to oxygen-starved conditions, an interpretation with implications for ocean anoxia. An alternative explanation for small phosphatic steinkerns is taphonomic. Stable carbonate fluorapatite selectively filled small voids, thus preserving small fossils, including larval/young mollusks. Reworking concentrated small phosphatic steinkerns from multiple generations while larger, unfilled calcareous shells were destroyed, resulting in small fossils progressively replacing larger fossils. With thin sections and insoluble residues, we document evidence that many of these steinkerns are incomplete (“teilsteinkerns”) recording small parts of larger, normal-sized animals, or juveniles, along with smaller species. This finding suggests that these fossil assemblages are taphonomically, not ecologically, size-limited. Based on the ecology of modern oxygen minimum zones in which shelled mollusks are rare, the presence of abundant shelled organisms actually argues against severe oxygen stress. Our results also imply that the process by which the “small shelly fossils” of the Cambrian were preserved continued into the Ordovician.