A gene signature of loss of oestrogen receptor (ER) function and oxidative stress links ER-positive breast tumours with an absent progesterone receptor and a poor prognosis

Prognostic gene signatures like the wound and hypoxia signature differ by assumptions of cellular growth. Although gene signatures show little overlap, they also track within the group of luminal breast tumours those with a high proliferation and poor prognosis. Oxidative stress is another assumption of cellular growth. It affects several pathological conditions through its influence on the regulation of protein kinases and signal transduction pathways. A comprehensive set of 62 core genes from cultured oestrogen- and oestrogen receptor-deprived epithelial breast cancer cells is responsive to three forms of oxidative stress. Evidence is presented that oxidative stress involves the development of an aggressive subset of primary oestrogen receptor-positive breast tumours

Preferential regulation of stably expressed genes in the human genome suggests a widespread expression buffering role of microRNAs

In this study, we comprehensively explored the stably expressed genes (SE genes) and fluctuant genes (FL genes) in the human genome by a meta-analysis of large scale microarray data. We found that these genes have distinct function distributions. miRNA targets are shown to be significantly enriched in SE genes by using propensity analysis of miRNA regulation, supporting the hypothesis that miRNAs can buffer whole genome expression fluctuation. The expression-buffering effect of miRNA is independent of the target site number within the 3'-untranslated region. In addition, we found that gene expression fluctuation is positively correlated with the number of transcription factor binding sites in the promoter region, which suggests that coordination between transcription factors and miRNAs leads to balanced responses to external perturbations

Nucleation and growth of Ag3Sn in Sn-Ag and Sn-Ag-Cu solder alloys

Large Ag3Sn plates in solder joints can affect the reliability of electronics, however, the factors affecting their nucleation and morphology are not well understood. Here, the faceted solidification of Ag3Sn was studied as a function of melt undercooling, revealing transitions from single crystal {001} plates to cyclic twinned plates and then to highly branched structures created by twin mediated branching. Real-time X-ray imaging proved that Ag3Sn cyclic twins come from a common point, indicating they initiate in the process of nucleation or in the very early stages of growth in the undercooled melt. Soldering to copper substrates significantly catalysed Ag3Sn nucleation. This is shown to be due to constitutional supercooling generated by Ag solute rejection into the liquid ahead of the Cu6Sn5 reaction layer, with additional contributions from geometrical catalysis in the grooves between Cu6Sn5 scallops and heterogeneous nucleation of Ag3Sn on Cu6Sn5. The relative ease of Ag3Sn nucleation on the Cu6Sn5 reaction layer is responsible for the large plates often reported in electronic solder joints

Novel anti-thrombotic agent for modulation of protein disulfide isomerase family member ERp57 for prophylactic therapy

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Quasi-periodic X-ray brightness fluctuations in an accreting millisecond pulsar

The relativistic plasma flows onto neutron stars that are accreting material from stellar companions can be used to probe strong-field gravity as well as the physical conditions in the supranuclear-density interiors of neutron stars. Plasma inhomogeneities orbiting a few kilometres above the stars are observable as X-ray brightness fluctuations on the millisecond dynamical timescale of the flows. Two frequencies in the kilohertz range dominate these fluctuations: the twin kilohertz quasi-periodic oscillations (kHz QPOs). Competing models for the origins of these oscillations (based on orbital motions) all predict that they should be related to the stellar spin frequency, but tests have been difficult because the spins were not unambiguously known. Here we report the detection of kHz QPOs from a pulsar whose spin frequency is known. Our measurements establish a clear link between kHz QPOs and stellar spin, but one not predicted by any current model. A new approach to understanding kHz QPOs is now required. We suggest that a resonance between the spin and general relativistic orbital and epicyclic frequencies could provide the observed relation between QPOs and spin.Comment: Published in the 2003 July 3 issue of Natur

Fjords as Aquatic Critical Zones (ACZs)

In recent decades, the land-ocean aquatic continuum, commonly defined as the interface, or transition zone, between terrestrial ecosystems and the open ocean, has undergone dramatic changes. On-going work has stressed the importance of treating Aquatic Critical Zones (ACZs) as a sensitive system needing intensive investigation. Here, we discuss fjords as an ACZ in the context of sedimentological, geochemical, and climatic impacts. These diverse physical features of fjords are key in controlling the sources, transport, and burial of organic matter in the modern era and over the Holocene. High sediment accumulation rates in fjord sediments allow for high-resolution records of past climate and environmental change where multiple proxies can be applied to fjord sediments that focus on either marine or terrestrial-derived components. Humans through land-use change and climatic stressors are having an impact on the larger carbon stores in fjords. Sediment delivery whether from accelerating erosion (e.g. mining, deforestation, road building, agriculture) or from sequestration of fluvial sediment behind dams has been seriously altered in the Anthropocene. Climate change affecting rainfall and river discharge into fjords will impact the thickness and extent of the low-salinity layer in the upper reaches of the fjord, slowing the rate of the overturning circulation and deep-water renewal – thereby impacting bottom water oxygen concentrations

Fabrication of Coaxial Si1−xGex Heterostructure Nanowires by O2 Flow-Induced Bifurcate Reactions

We report on bifurcate reactions on the surface of well-aligned Si1−xGex nanowires that enable fabrication of two different coaxial heterostructure nanowires. The Si1−xGex nanowires were grown in a chemical vapor transport process using SiCl4 gas and Ge powder as a source. After the growth of nanowires, SiCl4 flow was terminated while O2 gas flow was introduced under vacuum. On the surface of nanowires was deposited Ge by the vapor from the Ge powder or oxidized into SiO2 by the O2 gas. The transition from deposition to oxidation occurred abruptly at 2 torr of O2 pressure without any intermediate region and enables selectively fabricated Ge/Si1−xGex or SiO2/Si1−xGex coaxial heterostructure nanowires. The rate of deposition and oxidation was dominated by interfacial reaction and diffusion of oxygen through the oxide layer, respectively

More breast cancer genes?

A new gene associated with a high risk of breast cancer, termed BRCAX, may exist on chromosome 13q. Tumours from multicase Nordic breast cancer families, in which mutations in BRCA1 and BRCA2 had been excluded, were analyzed using comparative genomic hybridization in order to identify a region of interest, which was apparently confirmed and refined using linkage analysis on an independent sample. The present commentary discusses this work. It also asks why there should exist genetic variants associated with susceptibility to breast cancer other than mutations in BRCA1 and BRCA2, and what might be their modes of inheritance, allele frequencies and risks. Replication studies will be needed to clarify whether there really is a tumour suppressor gene other than BRCA2 on chromosome 13q

Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis

Increased glucose uptake mediated by glucose transporters and reliance on glycolysis are common features of malignant cells. Hypoxia-inducible factor-1α supports the adaptation of hypoxic cells by inducing genes related to glucose metabolism. The contribution of glucose transporter (GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to tumor behavior and their prognostic value in head and neck cancers remains unclear. The aim of this study was to examine the predictive value of GLUT1, GLUT3, and HIF-1α messenger RNA (mRNA)/protein expression as markers of tumor aggressiveness and prognosis in laryngeal cancer. The level of hypoxia/metabolic marker genes was determined in 106 squamous cell laryngeal cancer (SCC) and 73 noncancerous matched mucosa (NCM) controls using quantitative realtime PCR. The related protein levels were analyzed by Western blot. Positive expression of SLC2A1, SLC2A3, and HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer samples. Higher levels of mRNA/protein for GLUT1 and HIF-1α were noted in SCC compared to NCM (p<0.05). SLC2A1 was found to have a positive relationship with grade, tumor front grading (TFG) score, and depth and mode of invasion (p<0.05). SLC2A3 was related to grade and invasion type (p<0.05). There were also relationships of HIF-1α with pTNM, TFG scale, invasion depth and mode, tumor recurrences, and overall survival (p<0.05). In addition, more advanced tumors were found to be more likely to demonstrate positive expression of these proteins. In conclusion, the hypoxia/metabolic markers studied could be used as molecular markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory fund of the Department of Cytobiochemistry, University of Łódź, Poland (506/811), and by grant fromtheNational Science Council, Poland (N403 043 32/2326)