While tempering reactions under furnace conditions have been extensively studied, short-time tempering at higher temperatures, as might apply to induction tempering, has not been thoroughly explored. ...The mechanical behavior and phase development of short-time (1, 10, and 100 seconds) and conventionally (3600 seconds) tempered 4340 steel are compared at an equivalent degree of tempering defined by the Hollomon–Jaffe tempering parameter. The tempering parameter accurately predicts hardness values across short-time and conventional tempering conditions, but is less able to describe phase evolution associated with short-time tempering. Room temperature Charpy impact toughness and ductile-to-brittle transition temperature systematically improve with shorter tempering times at an equivalent tempering parameter. In particular, rapid tempering significantly increases toughness within the tempered martensite embrittlement regime. Relative to conventional tempering, shorter tempering times exhibit higher retained austenite content for a given tempering parameter, although no systematic or significant difference in cementite or transition carbide content is observed between time conditions. The retained austenite decomposition behavior indicates that the relationship between the classical tempering stages is altered at short tempering times, where increased overlap and/or “re-ordering” of stage II and III tempering are observed.
The influence of rapid tempering on cementite precipitation in 4340 steel was investigated within the tempered martensite embrittlement (TME) tempering regime. Cementite amount, size, and morphology, ...and matrix dislocation density were explored for rapid (1 s) and conventional (3600 s) tempering conditions with scanning electron microscopy (SEM) and x-ray diffraction (XRD), respectively, and compared at an equivalent degree of tempering (i.e., hardness). Rapid tempering resulted in an average refinement of cementite diameter by approximately 2–3 nm, and did not significantly alter cementite morphology, as determined by SEM, or phase fraction, as determined by Mössbauer spectroscopy, compared to conventional tempering. Previous studies have shown an improvement in toughness performance associated with the rapid tempering conditions explored here. Given the minimal carbide refinement observed in the present work, carbide size is not thought to be the primary microstructural factor in improving toughness properties of rapidly tempered conditions. Rather, impact toughness is likely influenced by differences in retained austenite content, as proposed in previous studies. The matrix dislocation content was similar between conventional and rapid tempering conditions at a given hardness, suggesting that the cementite refinement associated with rapid tempering was not promoted by the suppression of dislocation recovery.
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused, in most classic cases, by mutations in the X-linked methyl-CpG-binding protein 2 gene (
MECP2). A large degree of phenotypic ...variation has been observed in patients with RTT, both those with and without
MECP2 mutations. We describe a family consisting of a proband with a phenotype that showed considerable overlap with that of RTT, her identical twin sister with autistic disorder and mild-to-moderate intellectual disability, and a brother with profound intellectual disability and seizures. No pathogenic
MECP2 mutations were found in this family, and the Xq28 region that contains the
MECP2 gene was not shared by the affected siblings. Three other candidate regions were identified by microsatellite mapping, including 10.3 Mb at Xp22.31-pter between Xpter and
DXS1135, 19.7 Mb at Xp22.12-p22.11 between
DXS1135 and
DXS1214, and 16.4 Mb at Xq21.33 between
DXS1196 and
DXS1191. The
ARX and
CDKL5 genes, both of which are located within the Xp22 region, were sequenced in the affected family members, and a deletion of nucleotide 183 of the coding sequence (c.183delT) was identified in
CDKL5 in the affected family members. In a screen of 44 RTT cases, a single splice-site mutation, IVS13-1G→A, was identified in a girl with a severe phenotype overlapping RTT. In the mouse brain,
Cdkl5 expression overlaps—but is not identical to—that of
Mecp2, and its expression is unaffected by the loss of
Mecp2. These findings confirm
CDKL5 as another locus associated with epilepsy and X-linked mental retardation. These results also suggest that mutations in
CDKL5 can lead to a clinical phenotype that overlaps RTT. However, it remains to be determined whether
CDKL5 mutations are more prevalent in specific clinical subgroups of RTT or in other clinical presentations.
Polyphenol/Peptide Binding and Precipitation Charlton, Adrian J; Baxter, Nicola J; Khan, M. Lokman ...
Journal of agricultural and food chemistry,
03/2002, Letnik:
50, Številka:
6
Journal Article
Recenzirano
Polyphenols are largely responsible for the astringency and “mouthfeel” of tea and wine by their interactions with basic salivary proline-rich proteins. Astringency arises from precipitation of ...polyphenol/peptide complexes, which is an important protective mechanism in animals that consume polyphenols. This paper presents biophysical studies of the interactions between chemically defined polyphenols and peptides. It is shown that intermolecular binding is dominated by stacking of polyphenolic rings onto planar hydrophobic surfaces and is strengthened by multiple cooperative binding of polyphenolic rings. Affinities weaken at higher temperatures and are unaffected by pH between pH 3.8 and 6.0. Measurements of self-diffusion rates for peptides with increasing concentrations of polyphenol demonstrate that peptides become increasingly coated with polyphenol. When the coating is sufficiently extensive to provide cooperative polyphenol bridges, the peptide dimerizes and precipitates. Light scattering measurements and electron microscopy indicate that the insoluble particles fall into two discrete size classes of ca. 80 and 500 nm diameter. The larger particles are favored at higher temperature and pH, suggesting that the particles are in a colloidal state, with the smaller particles being stabilized by charge repulsion between particles, and that precipitation of the complexes may be a phase separation process. Keywords: Polyphenol; tannin; salivary protein; NMR; diffusion; light scattering
The detection of gravitational waves by Advanced LIGO and Advanced Virgo provides an opportunity to test general relativity in a regime that is inaccessible to traditional astronomical observations ...and laboratory tests. We present four tests of the consistency of the data with binary black hole gravitational waveforms predicted by general relativity. One test subtracts the best-fit waveform from the data and checks the consistency of the residual with detector noise. The second test checks the consistency of the low- and high-frequency parts of the observed signals. The third test checks that phenomenological deviations introduced in the waveform model (including in the post-Newtonian coefficients) are consistent with 0. The fourth test constrains modifications to the propagation of gravitational waves due to a modified dispersion relation, including that from a massive graviton. We present results both for individual events and also results obtained by combining together particularly strong events from the first and second observing runs of Advanced LIGO and Advanced Virgo, as collected in the catalog GWTC-1. We do not find any inconsistency of the data with the predictions of general relativity and improve our previously presented combined constraints by factors of 1.1 to 2.5. In particular, we bound the mass of the graviton to be mg≤4.7×10−23 eV/c2 (90% credible level), an improvement of a factor of 1.6 over our previously presented results. Additionally, we check that the four gravitational-wave events published for the first time in GWTC-1 do not lead to stronger constraints on alternative polarizations than those published previously.
The intrauterine environment is a major contributor to increased rates of metabolic disease in adults. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that affects 0.5%-2% ...of pregnant women and is characterized by increased bile acid levels in the maternal serum. The influence of ICP on the metabolic health of offspring is unknown. We analyzed the Northern Finland birth cohort 1985-1986 database and found that 16-year-old children of mothers with ICP had altered lipid profiles. Males had increased BMI, and females exhibited increased waist and hip girth compared with the offspring of uncomplicated pregnancies. We further investigated the effect of maternal cholestasis on the metabolism of adult offspring in the mouse. Females from cholestatic mothers developed a severe obese, diabetic phenotype with hepatosteatosis following a Western diet, whereas matched mice not exposed to cholestasis in utero did not. Female littermates were susceptible to metabolic disease before dietary challenge. Human and mouse studies showed an accumulation of lipids in the fetoplacental unit and increased transplacental cholesterol transport in cholestatic pregnancy. We believe this is the first report showing that cholestatic pregnancy in the absence of altered maternal BMI or diabetes can program metabolic disease in the offspring.
Genomes of Root-Knot Nematodes Bird, David McK; Williamson, Valerie M; Abad, Pierre ...
Annual review of phytopathology,
01/2009, Letnik:
47
Journal Article
Recenzirano
Plant-parasitic nematodes are the most destructive group of plant pathogens worldwide and are extremely challenging to control. The recent completion of two root-knot nematode genomes opens the way ...for a comparative genomics approach to elucidate the success of these parasites. Sequencing revealed that Meloidogyne hapla, a diploid that reproduces by facultative, meiotic parthenogenesis, encodes approximately 14,200 genes in a compact, 54 Mpb genome. Indeed, this is the smallest metazoan genome completed to date. By contrast, the 86 Mbp Meloidogyne incognita genome encodes approximately 19,200 genes. This species reproduces by obligate mitotic parthenogenesis and exhibits a complex pattern of aneuploidy. The genome includes triplicated regions and contains allelic pairs with exceptionally high degrees of sequence divergence, presumably reflecting adaptations to the strictly asexual reproductive mode. Both root-knot nematode genomes have compacted gene families compared with the free-living nematode Caenorhabditis elegans, and both encode large suites of enzymes that uniquely target the host plant. Acquisition of these genes, apparently via horizontal gene transfer, and their subsequent expansion and diversification point to the evolutionary history of these parasites. It also suggests new routes to their control.
Abstract MicroRNAs (miRNAs) are a large family of small non-coding RNAs which negatively control gene expression at both the mRNA and protein levels. The number of miRNAs identified is growing ...rapidly and approximately one-third is expressed in the brain where they have been shown to affect neuronal differentiation, synaptosomal complex localization and synapse plasticity, all functions thought to be disrupted in schizophrenia. Here we investigated the expression of 667 miRNAs (miRBase v.13) in the prefrontal cortex of individuals with schizophrenia (SZ, N = 35) and bipolar disorder (BP, N = 35) using a real-time PCR-based Taqman Low Density Array (TLDA). After extensive QC steps, 441 miRNAs were included in the final analyses. At a FDR of 10%, 22 miRNAs were identified as being differentially expressed between cases and controls, 7 dysregulated in SZ and 15 in BP. Using in silico target gene prediction programs, the 22miRNAs were found to target brain specific genes contained within networks overrepresented for neurodevelopment, behavior, and SZ and BP disease development. In an initial attempt to corroborate some of these predictions, we investigated the extent of correlation between the expressions of hsa-mir-34a, -132 and -212 and their predicted gene targets. mRNA expression of tyrosine hydroxylase (TH), phosphogluconate dehydrogenase (PGD) and metabotropic glutamate receptor 3 (GRM3) was measured in the SMRI sample. Hsa-miR-132 and -212 were negatively correlated with TH (p = 0.0001 and 0.0017) and with PGD (p = 0.0054 and 0.017, respectively).
The demographic transition—a change from high to low rates of mortality and fertility—has been more dramatic in East Asia during the twentieth century than in any other region or historical period. ...By introducing demographic variables into an empirical model of economic growth, this article shows that this transition has contributed substantially to East Asia's so-called economic miracle. The miracle occurred in part because East Asia's demographic transition resulted in its working-age population growing at a much faster rate than its dependent population during 1965–90, thereby expanding the per capita productive capacity of East Asian economies. This effect was not inevitable; rather, it occurred because East Asian countries had social, economic, and political institutions and policies that allowed them to realize the growth potential created by the transition. The empirical analyses indicate that population growth has a purely transitional effect on economic growth; this effect operates only when the dependent and working-age populations are growing at different rates. These results imply that future demographic change will tend to depress growth rates in East Asia, while it will promote more rapid economic growth in Southeast and South Asia.
Abstract Background & aims TGR5 (Gpbar-1) is a plasma membrane-bound bile acid receptor expressed in several tissues, including liver, intestine and brain. High levels of TGR5 mRNA have been detected ...in human and rodent placenta, however, localization of the TGR5 protein has not been studied in this tissue. We aimed at characterizing TGR5 expression in placental tissue and investigated the effect of bile acids and progesterone metabolites, which accumulate during intrahepatic cholestasis of pregnancy (ICP), on receptor expression and localization. Methods TGR5 mRNA levels and cell-specific localization were determined by quantitative PCR and immunofluorescence, respectively. Results In human term placentas, TGR5 was mainly localized in fetal macrophages and to a lower extent in trophoblasts. In placentas from ICP patients and pregnant rats with obstructive cholestasis a marked down-regulation of TGR5 mRNA expression was observed. However, the cell-specific distribution of the TGR5 protein was unaffected. Besides bile acids, progesterone and its metabolites (5α-pregnan-3α-ol-20-one/5α-pregnan-3β-ol-20-one), which increase in serum during ICP, were able to dose-dependently activate TGR5. In addition, progesterone metabolites but not their sulfated derivatives nor taurolithocholic acid, significantly down-regulated TGR5 mRNA and protein expression in isolated human macrophages and a macrophage-derived cell line. Conclusion Since fetal macrophages and trophoblast cells are exposed to changes in the flux of compounds across the placental barrier, the expression of TGR5 in these cells together with its sensitivity to bile acids and progesterone metabolites regarding receptor activity and mRNA expression suggest that TGR5 may play a role in the effect of maternal cholestasis on the placenta.
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