Effect of various dopant elements on primary graphite growth

Five spheroidal graphite cast irons were investigated, a usual ferritic grade and four pearlitic alloys containing Cu and doped with Sb, Sn and Ti. These alloys were remelted in a graphite crucible, leading to volatilization of the magnesium added for spheroidization and to carbon saturation of the liquid. The alloys were then cooled down and maintained at a temperature above the eutectic temperature. During this step, primary graphite could develop showing various features depending on the doping elements added. The largest effects were that of Ti which greatly reduces graphite nucleation and growth, and that of Sb which leads to rounded agglomerates instead of lamellar graphite. The samples have been investigated with secondary ion mass spectrometry to enlighten distribution of elements in primary graphite. SIMS analysis showed almost even distribution of elements, including Mg and Al (from the inoculant) in the ferritic grade, while uneven distribution was evident in all doped alloys. Investigations are going on to clarify if the uneven distribution is associated with structural defects in the graphite precipitates

CHARACTERISTICS OF THE INCREASED ADRENOCORTICAL FUNCTION OBSERVED IN MANY OBESE PATIENTS *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75360/1/j.1749-6632.1965.tb34805.x.pd

Two novel connexin32 mutations cause early onset X-linked Charcot-Marie-Tooth disease

<p>Abstract</p> <p>Background</p> <p>X-linked Charcot-Marie Tooth (CMT) is caused by mutations in the connexin32 gene that encodes a polypeptide which is arranged in hexameric array and form gap junctions.</p> <p>Methods</p> <p>We describe two novel mutations in the connexin32 gene in two Norwegian families.</p> <p>Results</p> <p>Family 1 had a c.225delG (R75fsX83) which causes a frameshift and premature stop codon at position 247. This probably results in a shorter non-functional protein structure. Affected individuals had an early age at onset usually in the first decade. The symptoms were more severe in men than women. All had severe muscle weakness in the legs. Several abortions were observed in this family. Family 2 had a c.536 G>A (C179Y) transition which causes a change of the highly conserved cysteine residue, i.e. disruption of at least one of three disulfide bridges. The mean age at onset was in the first decade. Muscle wasting was severe and correlated with muscle weakness in legs. The men and one woman also had symptom from their hands.</p> <p>The neuropathy is demyelinating and the nerve conduction velocities were in the intermediate range (25–49 m/s). Affected individuals had symmetrical clinical findings, while the neurophysiology revealed minor asymmetrical findings in nerve conduction velocity in 6 of 10 affected individuals.</p> <p>Conclusion</p> <p>The two novel mutations in the connexin32 gene are more severe than the majority of previously described mutations possibly due to the severe structural change of the gap junction they encode.</p

Diagnostische Bedeutung der Proteinbindung von Plasmacortisol, bestimmt durch Dextrangelfiltration

1. Mittels Dextrangelfiltration wurde nach Inkubation von markiertem Cortisol und Plasma der proteingebundene und der sog. freie Anteil (%) des endogenen Plasmacortisols ermittelt und bei gleichzeitiger fluorimetrischer Bestimmung der 11-OHCS auch die Menge proteingebundenen, bzw. sog. freien Cortisols (µg-%) berechnet. 2. Die diagnostische Brauchbarkeit der Methode wurde bei Patienten mit Nebennierenrindeninsuffizienz, mit Hypophysentumoren, nach Hypophysektomie, mit Cushing-Syndrom mit der fluorimetrischen Bestimmung der 11-OHCS verglichen. Die einfache Bestimmung der Cortisolbindung war bei hypophysektomierten Patienten der Bestimmung der 11-OHCS überlegen und entsprach der aufwendigeren ACTH-Belastung. 3. Falsch hohe fluorimetrische 11-OHCS-Spiegel im Plasma unter Spirolacton- oder Oestrogenbehandlung und in der Gravidität lassen sich durch Bestimmung der Cortisolbindung klären. Bei Schilddrüsenüberfunktion war das sog. freie Cortisol im Plasma relativ und absolut vermehrt, bei Schilddrüsenunterfunktion fand sich eine Zunahme des plasmaproteingebundenen Cortisols.1. Following incubation of labeled cortisol and plasma the percentages of protein bound and socalled free endogenous cortisol were determined by means of dextran gel filtration. 2. The diagnostic value of this method was compared with fluorimetric determinations of 11-OHCS for patients with adrenal insufficiency, Cushing-Syndrome, pituitary tumors and after hypophysectomy. In hypophysectomized patients the simple determination of protein bound cortisol was found to correlate well with diagnostic ACTH-infusion tests and to be more sensitive than fluorimetric determinations of 11-OHCS in 9 a.m. plasma. 3. Falsely elevated fluorimetric values of plasma 11-OHCS in patients treated with spirolactone or estrogens, resp. during pregnancy may be recognized through determination of cortisol binding. — In thyrotoxicosis socalled free cortisol was elevated, both relatively and absolutely; in hypothyroidism an increase of protein bound cortisol was found

Long interspersed nuclear element-1 hypomethylation in cancer: biology and clinical applications

Epigenetic changes in long interspersed nuclear element-1s (LINE-1s or L1s) occur early during the process of carcinogenesis. A lower methylation level (hypomethylation) of LINE-1 is common in most cancers, and the methylation level is further decreased in more advanced cancers. Consequently, several previous studies have suggested the use of LINE-1 hypomethylation levels in cancer screening, risk assessment, tumor staging, and prognostic prediction. Epigenomic changes are complex, and global hypomethylation influences LINE-1s in a generalized fashion. However, the methylation levels of some loci are dependent on their locations. The consequences of LINE-1 hypomethylation are genomic instability and alteration of gene expression. There are several mechanisms that promote both of these consequences in cis. Therefore, the methylation levels of different sets of LINE-1s may represent certain phenotypes. Furthermore, the methylation levels of specific sets of LINE-1s may indicate carcinogenesis-dependent hypomethylation. LINE-1 methylation pattern analysis can classify LINE-1s into one of three classes based on the number of methylated CpG dinucleotides. These classes include hypermethylation, partial methylation, and hypomethylation. The number of partial and hypermethylated loci, but not hypomethylated LINE-1s, is different among normal cell types. Consequently, the number of hypomethylated loci is a more promising marker than methylation level in the detection of cancer DNA. Further genome-wide studies to measure the methylation level of each LINE-1 locus may improve PCR-based methylation analysis to allow for a more specific and sensitive detection of cancer DNA or for an analysis of certain cancer phenotypes

Spatially Explicit Analysis of Metal Transfer to Biota: Influence of Soil Contamination and Landscape

Concepts and developments for a new field in ecotoxicology, referred to as “landscape ecotoxicology,” were proposed in the 1990s; however, to date, few studies have been developed in this emergent field. In fact, there is a strong interest in developing this area, both for renewing the concepts and tools used in ecotoxicology as well as for responding to practical issues, such as risk assessment. The aim of this study was to investigate the spatial heterogeneity of metal bioaccumulation in animals in order to identify the role of spatially explicit factors, such as landscape as well as total and extractable metal concentrations in soils. Over a smelter-impacted area, we studied the accumulation of trace metals (TMs: Cd, Pb and Zn) in invertebrates (the grove snail Cepaea sp and the glass snail Oxychilus draparnaudi) and vertebrates (the bank vole Myodes glareolus and the greater white-toothed shrew Crocidura russula). Total and CaCl2-extractable concentrations of TMs were measured in soils from woody patches where the animals were captured. TM concentrations in animals exhibited a high spatial heterogeneity. They increased with soil pollution and were better explained by total rather than CaCl2-extractable TM concentrations, except in Cepaea sp. TM levels in animals and their variations along the pollution gradient were modulated by the landscape, and this influence was species and metal specific. Median soil metal concentrations (predicted by universal kriging) were calculated in buffers of increasing size and were related to bioaccumulation. The spatial scale at which TM concentrations in animals and soils showed the strongest correlations varied between metals, species and landscapes. The potential underlying mechanisms of landscape influence (community functioning, behaviour, etc.) are discussed. Present results highlight the need for the further development of landscape ecotoxicology and multi-scale approaches, which would enhance our understanding of pollutant transfer and effects in ecosystems

Evolutionary diversity and developmental regulation of X-chromosome inactivation

X-chromosome inactivation (XCI) results in the transcriptional silencing of one X-chromosome in females to attain gene dosage parity between XX female and XY male mammals. Mammals appear to have developed rather diverse strategies to initiate XCI in early development. In placental mammals XCI depends on the regulatory noncoding RNA X-inactive specific transcript (Xist), which is absent in marsupials and monotremes. Surprisingly, even placental mammals show differences in the initiation of XCI in terms of Xist regulation and the timing to acquire dosage compensation. Despite this, all placental mammals achieve chromosome-wide gene silencing at some point in development, and this is maintained by epigenetic marks such as chromatin modifications and DNA methylation. In this review, we will summarise recent findings concerning the events that occur downstream of Xist RNA coating of the inactive X-chromosome (Xi) to ensure its heterochromatinization and the maintenance of the inactive state in the mouse and highlight similarities and differences between mammals

Gene expression patterns associated with blood-feeding in the malaria mosquito Anopheles gambiae

BACKGROUND: Blood feeding, or hematophagy, is a behavior exhibited by female mosquitoes required both for reproduction and for transmission of pathogens. We determined the expression patterns of 3,068 ESTs, representing ~2,000 unique gene transcripts using cDNA microarrays in adult female Anopheles gambiae at selected times during the first two days following blood ingestion, at 5 and 30 min during a 40 minute blood meal and at 0, 1, 3, 5, 12, 16, 24 and 48 hours after completion of the blood meal and compared their expression to transcript levels in mosquitoes with access only to a sugar solution. RESULTS: In blood-fed mosquitoes, 413 unique transcripts, approximately 25% of the total, were expressed at least two-fold above or below their levels in the sugar-fed mosquitoes, at one or more time points. These differentially expressed gene products were clustered using k-means clustering into Early Genes, Middle Genes, and Late Genes, containing 144, 130, and 139 unique transcripts, respectively. Several genes from each group were analyzed by quantitative real-time PCR in order to validate the microarray results. CONCLUSION: The expression patterns and annotation of the genes in these three groups (Early, Middle, and Late genes) are discussed in the context of female mosquitoes' physiological responses to blood feeding, including blood digestion, peritrophic matrix formation, egg development, and immunity

Epigenetics and airways disease

Epigenetics is the term used to describe heritable changes in gene expression that are not coded in the DNA sequence itself but by post-translational modifications in DNA and histone proteins. These modifications include histone acetylation, methylation, ubiquitination, sumoylation and phosphorylation. Epigenetic regulation is not only critical for generating diversity of cell types during mammalian development, but it is also important for maintaining the stability and integrity of the expression profiles of different cell types. Until recently, the study of human disease has focused on genetic mechanisms rather than on non-coding events. However, it is becoming increasingly clear that disruption of epigenetic processes can lead to several major pathologies, including cancer, syndromes involving chromosomal instabilities, and mental retardation. Furthermore, the expression and activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in the airways of patients with respiratory disease. The development of new diagnostic tools might reveal other diseases that are caused by epigenetic alterations. These changes, despite being heritable and stably maintained, are also potentially reversible and there is scope for the development of 'epigenetic therapies' for disease

Sexual dimorphism in cancer.

The incidence of many types of cancer arising in organs with non-reproductive functions is significantly higher in male populations than in female populations, with associated differences in survival. Occupational and/or behavioural factors are well-known underlying determinants. However, cellular and molecular differences between the two sexes are also likely to be important. In this Opinion article, we focus on the complex interplay that sex hormones and sex chromosomes can have in intrinsic control of cancer-initiating cell populations, the tumour microenvironment and systemic determinants of cancer development, such as the immune system and metabolism. A better appreciation of these differences between the two sexes could be of substantial value for cancer prevention as well as treatment