Miracle-dz/UniFAR-FTUs huggingface dataset:
A Comprehensive Analysis of Breast Cancer News Coverage in Leading Media Outlets Focusing on Environmental Risks and Prevention

Breast cancer has a high profile in the news media, which are a major source of information for cancer patients and the general public. To determine the nature of breast cancer news coverage available to audiences, particularly on the topics of environmental risks and prevention, this content analysis measured a broad array of dimensions in 231 stories appearing in nine leading newspapers, newsmagazines, and television networks in 2003 and 2004. One fourth of all stories reported on various risks such as hormone replacement therapy (HRT) use. Very few items specifically addressed risks related to controllable lifestyle practices such as prepubertal obesity or chemical contaminants in the environment. About one third of the stories included prevention content, primarily focusing narrowly on use of pharmaceutical products. Little information described risk reduction via other individual preventive behaviors (e.g., diet, exercise, and smoking), parental protective measures, or collective actions to combat contamination sites. The more traditional categories of prevalence, detection, and treatment were featured in one third, one quarter, and two fifths of the news items, respectively. There were twice as many stories featuring personal narratives as statistical figures, and two thirds of all the news items cited expert medical professionals, researchers, or organizations. Implications of these findings and directions for future research are addressed.
Dosimetry estimations for 123I-IAZA in healthy volunteers.

UNLABELLED 123I-Labeled iodoazomycin arabinoside (IAZA) is a marker of hypoxia in vivo. It has been used clinically to image hypoxic tissue in solid tumors, peripheral vascular disease of diabetic origin, blunt brain trauma, and rheumatoid joints and in an animal model of cerebrovascular disease. The radiation dose biodistribution for 123I-IAZA was studied to assess and characterize its suitability as a clinical radiopharmaceutical. METHODS Six healthy volunteers each received a nominal 185-MBq (5 mCi) dose of 123I-IAZA administered as a slow (1-3 min) intravenous injection in the arm. Anterior and posterior whole-body planar images were acquired for each volunteer beginning immediately after injection and at 1-2, 3-4, 6-8, and 20-24 h after injection. Venous blood samples (0 h predose through 28 h after dosing) and 28-h cumulative urine samples were taken from each volunteer for pharmacokinetic analysis. Radiation dose estimates were performed for all volunteers, with "reference adult" (for men) and "adult female" (for women) phantoms, and both the International Commission on Radiological Protection 30 gastrointestinal tract model and the dynamic bladder model, using the MIRDOSE3 program. Two sets of estimates, 1 using a pharmacokinetic analysis of total serum radioactivity and 1 based on scintigraphic image data, were obtained for each volunteer after 123I-IAZA administration. RESULTS Two compartments were discernible by pharmacokinetic analysis, and 4 compartments were discernible by image analysis. The urinary bladder wall received the greatest radiation dose (6.3E-02 +/- 8.7E-03 mGy/MBq), followed by the upper large intestinal wall (5.6E-02 +/- 1.2E-02 mGy/MBq), the lower large intestinal wall (5.0E-02 +/- 1.2E-02 mGy/MBq), and the thyroid (4.4E-02 +/- 1.4E-02 mGy/MBq). Approximately 90% of physiologically eliminated radioactivity was excreted through the kidneys. Radioactivity entering the intestinal tract from the gallbladder constituted <10% of biologically eliminated activity. CONCLUSION The dosimetric analysis of 123I-IAZA in 6 healthy volunteers indicated that both disposition kinetics and radiation dosimetry support its clinical use for imaging tissue hypoxia.
A Pivotal Role of Endothelial-Specific NF-κB Signaling in the Pathogenesis of Septic Shock and Septic Vascular Dysfunction1

Although the role of NF-κB in the pathogenesis of sepsis and septic shock has been extensively studied, little is known about the causative contribution of endothelial-intrinsic NF-κB to these pathological processes. In this study, we used transgenic (TG) mice (on FVB genetic background) that conditionally overexpress the NF-κB inhibitor, mutant I-κBα, selectively on endothelium and their transgene-negative littermates (wild type (WT)) to define the causative role of endothelial-specific NF-κB signaling in septic shock and septic vascular dysfunction. In WT mice, LPS challenge caused systemic hypotension, a significantly blunted vasoconstrictor response to norepinephrine, and an impaired endothelium-dependent vasodilator response to acetylcholine, concomitant with a markedly increased aortic inducible NO synthase expression, significantly elevated plasma and aortic levels of nitrite/nitrate, increased aortic TNF-α expression, and decreased aortic endothelial NO synthase (eNOS) expression. In TG mice whose endothelial NF-κB was selectively blocked, LPS caused significantly less hypotension and no impairments in vasoconstrictor and endothelium-dependent vasodilator responses, associated with significantly reduced aortic inducible NO synthase expression, decreased plasma and aortic levels of nitrite/nitrate, reduced aortic TNF-α expression, and increased aortic eNOS expression. TNF-α knockout mice prevented LPS-induced eNOS down-regulation. WT mice subjected to cecal ligation and puncture showed significant systemic hypotension, which was prevented in TG mice. Our data show that selective blockade of endothelial-intrinsic NF-κB pathway is sufficient to abrogate the cascades of molecular events that lead to septic shock and septic vascular dysfunction, demonstrating a pivotal role of endothelial-specific NF-κB signaling in the pathogenesis of septic shock and septic vascular dysfunction.
Chromosomal DNA transfer in Mycobacterium smegmatis is mechanistically different from classical Hfr chromosomal DNA transfer

Classical conjugal DNA transfer of chromosomal DNA in bacteria requires the presence of a cis‐acting site, oriT, in the chromosome. Acquisition of an oriT occurs if a conjugative plasmid integrates into the chromosome to form an Hfr donor strain, which can transfer extensive regions of chromosomal DNA. Because oriT sequences are unique, and because transfer occurs in a 5′ to 3′ direction, the frequency with which a particular gene is inherited by the recipient depends on the gene's location: those closest to the 3′ side of oriT are transferred most efficiently. In addition, as the entire chromosome must be transferred to regenerate oriT, Hfr transconjugants never become donors. Here we describe novel aspects of a chromosomal DNA transfer system in Mycobacterium smegmatis. We demonstrate that there are multiple transfer initiations from a donor chromosome and, as a result, the inheritance of any gene is location‐independent. Transfer is not contiguous; instead, multiple non‐linked segments of DNA can be inherited in a recipient. However, we show that, with appropriate selection, segments of DNA at least 266 kb in length can be transferred. In further contrast to Hfr transfer, transconjugants can become donors, suggesting that the recipient chromosome contains multiple cis‐acting sequences required for transfer, but lacks the trans‐acting transfer functions. We exploit these observations to map a donor‐determining locus in the M. smegmatis chromosome using genetic linkage analysis. Together, these studies further underline the unique nature of the M. smegmatis chromosomal transfer system.
Histone deacetylase inhibition‐mediated post‐translational elevation of p27KIP1 protein levels is required for G1 arrest in fibroblasts

Butyrate, a non‐toxic short‐chain fatty acid (SCFA) and inhibitor of histone deacetylase (HDAC), has potential as an anti‐tumor agent because it imposes a reversible G1 block in normal cells yet induces apoptosis in tumor lines. As a potent reactivator of fetal globin transcription, butyrate is used clinically in the treatment of hemoglobinopathies. The anti‐proliferative effect of butyrate and its derivatives on in vivo erythroid cell maturation, however, has limited their utility. The molecular mechanisms underlying the G1 arrest induced by butyrate and related SCFAs remain unclear. One model, drawing on tumor cell data, proposes that HDAC inhibition and subsequent transcriptional induction of cyclin‐dependent kinase inhibitor (CKI) p21CIP are required. However, because of potentially confounding genetic mutations present in tumor models, we examined SCFA effects on CKIs in a non‐transformed growth control model. Using murine 3T3 fibroblasts, we find p27KIP1 is also strongly induced. Unlike previously described effects of butyrate and HDAC inhibition on p21CIP, p27KIP1 induction did not occur at the transcriptional level; instead, the stability of the p27KIP1 protein increased. Other structurally unrelated HDAC inhibitors, including trichostatin A (TSA), induced p27KIP1 similarly. p27KIP1 was found in cyclin E/Cdk2 complexes, concomitant with suppression of cdk2 activity. Elevation of p27KIP1 is required for the observed G1 blockade, as p27KIP1‐deficient fibroblasts were resistant to HDAC inhibition‐induced arrest. These data suggest a novel activity for HDAC inhibitors and demonstrate a critical role for p27KIP1 in mediating G1 arrest in response to these drugs. © 2005 Wiley‐Liss, Inc.
Comparison of five radiographic views for assessment of the medial aspect of the humeral condyle in dogs with osteochondritis dissecans.

OBJECTIVE To compare 5 radiographic views for the detection of osteochondritis dissecans (OCD) in dogs with signs of elbow joint pain. ANIMALS 53 dogs (100 elbow joints) with forelimb lameness and signs of elbow joint pain. PROCEDURES Mediolateral (ML), flexed ML, craniocaudal (CC), craniolateral-caudomedial oblique (Cr15L-CdMO), and distomedial-proximolateral oblique (Di35M-PrLO) radiographic views of the 100 elbow joints were obtained. Four examiners graded radiographs with regard to elbow joint OCD. Joints were assessed by use of arthroscopy. Receiver operating characteristic (ROC) curves, kappa measure of agreement, and Fisher exact tests for association between median diagnostic value and actual status were computed. RESULTS 47 joints had an abnormal medial aspect of the humeral condyle (MAHC), and among them, 11 had OCD. The presence of fractures of the medial coronoid process was significantly and positively correlated with the presence of abnormalities of the MAHC (r = 0.40), but was negatively correlated with the presence of OCD (r = -0.32). At 95% specificity, median sensitivities to detect OCD were 57% for Cr15L-CdMO, 56% for CC, 10% for flexed ML, 7% for ML, and 4% for Di35M-PrLO views. The areas under the ROC curves were significantly larger for the Cr15L-CdMO and CC views than for the ML, flexed ML, and Di35M-PrLO views for the detection of OCD. Only the Cr15L-CdMO and CC views allowed accurate detection of OCD. CONCLUSIONS AND CLINICAL RELEVANCE In dogs with signs of elbow joint pain, the Cr15L-CdMO view is excellent and the CC view was good for detection of OCD.
Patterns of axonal branching of neurons of the substantia nigra pars reticulata and pars lateralis in the rat

Axons from neurons of the rat substantia nigra pars reticulata (SNr) and pars lateralis (SNl) were traced after injecting their cell body with biotinylated dextran amine. Thirty‐two single axons were reconstructed from serial sagittal sections with a camera lucida, whereas four other SNr axons were reconstructed in the coronal plane to determine whether they innervate the contralateral hemisphere. Four distinct types of SNr projection neurons were identified based on their main axonal targets: type I neurons that project to the thalamus; type II neurons that target the thalamus, the superior colliculus (SC), and the pedunculopontine tegmental nucleus (PPTg); type III neurons that project to the periaqueductal gray matter and the thalamus; and type IV neurons that target the deep mesencephalic nucleus (DpMe) and the SC. The axons of the SNl showed the same branching patterns as SNr axons of types I, II, and IV. The coronal reconstructions demonstrated that SNr neurons innervate the thalamus, the SC, and the DpMe bilaterally. At the thalamic level, SNr and SNl axons targeted preferentially the ventral medial, ventral lateral, paracentral, parafascicular, and mediodorsal nuclei. Axons reaching the SC arborized selectively within the deep layers of this structure. Our results reveal that the SNr and SNl harbor several subtypes of projection neurons endowed with a highly patterned set of axon collaterals. This organization allows single neurons of these output structures of the basal ganglia to exert a multifaceted influence on a wide variety of diencephalic and midbrain structures. J. Comp. Neurol. 492:349–369, 2005. © 2005 Wiley‐Liss, Inc.
Dnmt3b recruitment through E2F6 transcriptional repressor mediates germ-line gene silencing in murine somatic tissues

Methylation of cytosine residues within the CpG dinucleotide in mammalian cells is an important mediator of gene expression, genome stability, X-chromosome inactivation, genomic imprinting, chromatin structure, and embryonic development. The majority of CpG sites in mammalian cells is methylated in a nonrandom fashion, raising the question of how DNA methylation is distributed along the genome. Here, we focused on the functions of DNA methyltransferase-3b (Dnmt3b), of which deregulated activity is linked to several human pathologies. We generated Dnmt3b hypomorphic mutant mice with reduced catalytic activity, which first revealed a deregulation of Hox genes expression, consistent with the observed homeotic transformations of the posterior axis. In addition, analysis of deregulated expression programs in Dnmt3b mutant embryos, using DNA microarrays, highlighted illegitimate activation of several germ-line genes in somatic tissues that appeared to be linked directly to their hypomethylation in mutant embryos. We provide evidence that these genes are direct targets of Dnmt3b. Moreover, the recruitment of Dnmt3b to their proximal promoter is dependant on the binding of the E2F6 transcriptional repressor, which emerges as a common hallmark in the promoters of genes found to be up-regulated as a consequence of impaired Dnmt3b activity. Therefore, our results unraveled a coordinated regulation of genes involved in meiosis, through E2F6-dependant methylation and transcriptional silencing in somatic tissues.
The small G protein RAS2 is involved in the metabolic compensation of the circadian clock in the circadian model Neurospora crassa

Accumulating evidence from both experimental and clinical investigations indicates a tight interaction between metabolism and circadian timekeeping; however, knowledge of the underlying mechanism is still incomplete. Metabolic compensation allows circadian oscillators to run with a constant speed at different substrate levels and, therefore, is a substantial criterion of a robust rhythm in a changing environment. Because previous data have suggested a central role of RAS2-mediated signaling in the adaptation of yeast to different nutritional environments, we examined the involvement of RAS2 in the metabolic regulation of the clock in the circadian model organism Neurospora crassa. We show that, in a ras2-deficient strain, the period is longer than in the control. Moreover, unlike in the WT, in Δras2, operation of the circadian clock was affected by glucose; compared with starvation conditions, the period was longer and the oscillation of expression of the frequency (frq) gene was dampened. In constant darkness, the delayed phosphorylation of the FRQ protein and the long-lasting accumulation of FRQ in the nucleus were in accordance with the longer period and the less robust rhythm in the mutant. Although glucose did not affect the subcellular distribution of FRQ in the WT, highly elevated FRQ levels were detected in the nucleus in Δras2. RAS2 interacted with the RAS-binding domain of the adenylate cyclase in vitro, and the cAMP analogue 8-bromo-cyclic AMP partially rescued the circadian phenotype in vivo. We therefore propose that RAS2 acts via a cAMP-dependent pathway and exerts significant metabolic control on the Neurospora circadian clock.
The structure of “defective in induced resistance” protein of Arabidopsis thaliana, DIR1, reveals a new type of lipid transfer protein

Screening of transfer DNA (tDNA) tagged lines of Arabidopsis thaliana for mutants defective in systemic acquired resistance led to the characterization of dir1‐1 (defective in induced resistance [systemic acquired resistance, SAR]) mutant. It has been suggested that the protein encoded by the dir1 gene, i.e., DIR1, is involved in the long distance signaling associated with SAR. DIR1 displays the cysteine signature of lipid transfer proteins, suggesting that the systemic signal could be lipid molecules. However, previous studies have shown that this signature is not sufficient to define a lipid transfer protein, i.e., a protein capable of binding lipids. In this context, the lipid binding properties and the structure of a DIR1–lipid complex were both determined by fluorescence and X‐ray diffraction. DIR1 is able to bind with high affinity two monoacylated phospholipids (dissociation constant in the nanomolar range), mainly lysophosphatidyl cholines, side‐by‐side in a large internal tunnel. Although DIR1 shares some structural and lipid binding properties with plant LTP2, it displays some specific features that define DIR1 as a new type of plant lipid transfer protein. The signaling function associated with DIR1 may be related to a specific lipid transport that needs to be characterized and to an additional mechanism of recognition by a putative receptor, as the structure displays on the surface the characteristic PxxP structural motif reminiscent of SH3 domain signaling pathways.
Clinical and endoscopic characteristics of acute haemorrhagic rectal ulcer, and endoscopic haemostatic treatment: a retrospective study of 95 patients

Aim Acute haemorrhagic rectal ulcer (AHRU) is characterized by sudden onset of painless and massive rectal bleeding in elderly bedridden patients who have serious illness. Endoscopic diagnosis and management of AHRU is, however, still controversial. We retrospectively investigated 95 AHRU patients to elucidate the clinical characteristics, endoscopic findings and haemostatic strategies.
Gene expression profile of human Down syndrome leukocytes.

AIM Identification of differences in the gene expression patterns of Down syndrome and normal leukocytes. METHODS We constructed the first Down syndrome leukocyte serial analysis of gene expression (SAGE) library from a 28 year-old patient. This library was analyzed and compared with a normal leukocyte SAGE library using the eSAGE software. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to validate the results. RESULTS We found that a large number of unidentified transcripts were overexpressed in Down syndrome leukocytes and some transcripts coding for growth factors (e.g. interleukin 8, IL-8), ribosomaproteins (e.g. L13a, L29, and L37), and transcription factors (e.g., Jun B, Jun D, and C/EBP beta) were underexpressed. The SAGE data were successfully validated for the genes IL-8, CXCR4, BCL2A1, L13a, L29, L37, and GTF3A using RT-PCR. CONCLUSION Our analysis identified significant changes in the expression pattern of Down syndrome leukocytes compared with normal ones, including key regulators of growth and proliferation, ribosomal proteins, and a large number of overexpressed transcripts that were not matched in UniGene clusters and that may represent novel genes related to Down syndrome. This study offers a new insight into transcriptional changes in Down syndrome leukocytes and indicates candidate genes for further investigations into the molecular mechanism of Down syndrome pathology.
Fluorescence‐activated sorting of fixed nuclei: a general method for studying nuclei from specific cell populations that preserves post‐translational modifications

Long‐lasting brain alterations that underlie learning and memory are triggered by synaptic activity. How activity can exert long‐lasting effects on neurons is a major question in neuroscience. Signalling pathways from cytoplasm to nucleus and the resulting changes in transcription and epigenetic modifications are particularly relevant in this context. However, a major difficulty in their study comes from the cellular heterogeneity of brain tissue. A promising approach is to directly purify identified nuclei. Using mouse striatum we have developed a rapid and efficient method for isolating cell type‐specific nuclei from fixed adult brain (fluorescence‐activated sorting of fixed nuclei; FAST‐FIN). Animals are quickly perfused with a formaldehyde fixative that stops enzymatic reactions and maintains the tissue in the state it was at the time of death, including nuclear localisation of soluble proteins such as GFP and differences in nuclear size between cell types. Tissue is subsequently dissociated with a Dounce homogeniser and nuclei prepared by centrifugation in an iodixanol density gradient. The purified fixed nuclei can then be immunostained with specific antibodies and analysed or sorted by flow cytometry. Simple criteria allow distinction of neurons and non‐neuronal cells. Immunolabelling and transgenic mice that express fluorescent proteins can be used to identify specific cell populations, and the nuclei from these populations can be efficiently isolated, even rare cell types such as parvalbumin‐expressing interneurons. FAST‐FIN allows the preservation and study of dynamic and labile post‐translational protein modifications. It should be applicable to other tissues and species, and allow study of DNA and its modifications.
Molecular epidemiology of ‘Norwalk‐like viruses’ associated with gastroenteritis outbreaks in New Zealand

Outbreaks of gastroenteritis are a major public health problem in New Zealand. The introduction of molecular detection methods has now shown that the ‘Norwalk‐like viruses’ (NLVs) are the major cause of food and waterborne nonbacterial gastroenteritis. Reverse transcription and polymerase chain reaction (RT‐PCR) were used to determine the presence of NLVs in faecal specimens from 83 nonbacterial gastroenteritis outbreaks occurring in New Zealand between August 1995 and July 1999. Further characterisation of the NLVs for epidemiological purposes was carried out by dot blot DNA hybridisation and DNA sequencing of representative outbreak strains. The majority of NLV strains occurring in New Zealand since August 1995 are similar to those occurring overseas. The predominant New Zealand strain is genetically similar to the Bristol/Lordsdale virus group. Several New Zealand outbreaks were attributed to Auckland virus, a Mexico‐like NLV strain identified as the most likely cause of gastroenteritis after consumption of contaminated oysters in 1994. A new strain, designated Napier virus, has been identified in six outbreaks since 1996. A number of strains closely resembling internationally recognised strains, including Southampton virus, Saratoga virus; Desert Shield virus and Melksham virus have been associated with gastroenteritis outbreaks across New Zealand. Application of these typing methods has provided information on disease transmission for epidemiological investigations of public health significance. J. Med. Virol. 64:58–66, 2001. © 2001 Wiley‐Liss, Inc.