249 research outputs found

    Renal cell carcinoma metastasizing to solitary fibrous tumor of the pleura: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>A tumor metastasizing to another malignancy is an uncommon phenomenon. Since it was first described in 1902, there have been fewer than 200 cases reported in the literature, with lung cancer metastasizing to renal cell carcinoma being the most frequently described pattern. Here we report a case of a solitary fibrous tumor of the lung acting as the recipient for a renal cell carcinoma. To our knowledge, this is the first reported case of such a combination and the second case involving a solitary fibrous tumor.</p> <p>Case presentation</p> <p>A 58-year-old Caucasian man who developed a persistent dry cough presented to our hospital. Imaging studies revealed a large pleural-based mass in the left lung. A biopsy of the mass showed a spindle-cell lesion consistent with a solitary fibrous tumor. The patient underwent surgical excision of the 13 cm mass. The pathological examination confirmed the diagnosis of a solitary fibrous tumor but also demonstrated discrete foci of metastatic renal cell carcinoma. Until that point, a primary renal cell carcinoma tissue diagnosis had not been made and the initial radiological work-up was inconclusive.</p> <p>Conclusion</p> <p>Awareness of the unusual phenomenon of tumor-to-tumor metastasis is important for practicing surgical pathologists, particularly in the evaluation of a mass lesion showing bimodal histology. This case also highlights the importance of careful examination of surgical specimens, as minute and unusual findings can direct patient care.</p

    An experimental investigation into resonance dry grinding of hardened steel and nickel alloys with element of MQL

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    Current policies on environmental issues put extra pressures on manufacturing processes to be resource efficient and eco-friendly. However, in grinding processes, large amounts of cutting fluids are used. These fluids are not environmental friendly thus require proper management before disposal with associated cost. Hence, this work sets to explore low-frequency vibration in grinding in order to improve coolant application in conventional grinding at the first stage with the aim to introduce this into high efficiency deep grinding (HEDG) at latter stage. An attempt is made to grind nickel alloys with minimum quantity lubricant (MQL) as oppose to flood cooling. To achieve this with minimum alterations to the machine tool, a piezo-driven workpiece holder was developed for surface grinding. This simple innovative workpiece holder allowed oscillating during actual grinding process. However, this paper presents the results of low-frequency oscillatory grinding in dry and near-dry conditions. The response of the machine tool spindle unit is presented alongside with the workpiece holder response. In this investigation, hardened steels and nickel alloys were ground with vibration assistance. The grinding forces are illustrated together with the surface finish. The wheel performance is given in terms of grinding ratio

    Synthesis, Biological Evaluation and Mechanism Studies of Deoxytylophorinine and Its Derivatives as Potential Anticancer Agents

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    Previous studies indicated that (+)-13a-(S)-Deoxytylophorinine (1) showed profound anti-cancer activities both in vitro and in vivo and could penetrate the blood brain barrier to distribute well in brain tissues. CNS toxicity, one of the main factors to hinder the development of phenanthroindolizidines, was not obviously found in 1. Based on its fascinating activities, thirty-four derivatives were designed, synthesized; their cytotoxic activities in vitro were tested to discover more excellent anticancer agents. Considering the distinctive mechanism of 1 and interesting SAR of deoxytylophorinine and its derivatives, the specific impacts of these compounds on cellular progress as cell signaling transduction pathways and cell cycle were proceeded with seven representative compounds. 1 as well as three most potent compounds, 9, 32, 33, and three less active compounds, 12, 16, 35, were selected to proform this study to have a relatively deep view of cancer cell growth-inhibitory characteristics. It was found that the expressions of phospho-Akt, Akt, phospho-ERK, and ERK in A549 cells were greater down-regulated by the potent compounds than by the less active compounds in the Western blot analysis. To the best of our knowledge, this is the first report describing phenanthroindolizidines alkaloids display influence on the crucial cell signaling proteins, ERK. Moreover, the expressions of cyclin A, cyclin D1 and CDK2 proteins depressed more dramatically when the cells were treated with 1, 9, 32, and 33. Then, these four excellent compounds were subjected to flow cytometric analysis, and an increase in S-phase was observed in A549 cells. Since the molecular level assay results of Western blot for phospho-Akt, Akt, phospho-ERK, ERK, and cyclins were relevant to the potency of compounds in cellular level, we speculated that this series of compounds exhibit anticancer activities through blocking PI3K and MAPK signaling transduction pathways and interfering with the cell cycle progression

    Lysine-Rich Extracellular Rings Formed by hΞ²2 Subunits Confer the Outward Rectification of BK Channels

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    The auxiliary Ξ² subunits of large-conductance Ca2+-activated K+ (BK) channels greatly contribute to the diversity of BK (mSlo1 Ξ±) channels, which is fundamental to the adequate function in many tissues. Here we describe a functional element of the extracellular segment of hΞ²2 auxiliary subunits that acts as the positively charged rings to modify the BK channel conductance. Four consecutive lysines of the hΞ²2 extracellular loop, which reside sufficiently close to the extracellular entryway of the pore, constitute three positively charged rings. These rings can decrease the extracellular K+ concentration and prevent the Charybdotoxin (ChTX) from approaching the extracellular entrance of channels through electrostatic mechanism, leading to the reduction of K+ inflow or the outward rectification of BK channels. Our results demonstrate that the lysine rings formed by the hΞ²2 auxiliary subunits influences the inward current of BK channels, providing a mechanism by which current can be rapidly diminished during cellular repolarization. Furthermore, this study will be helpful to understand the functional diversity of BK channels contributed by different auxiliary Ξ² subunits

    Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells.

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    Follicular helper T (TFH) cells are expanded in systemic lupus erythematosus, where they are required to produce high affinity autoantibodies. Eliminating TFH cells would, however compromise the production of protective antibodies against viral and bacterial pathogens. Here we show that inhibiting glucose metabolism results in a drastic reduction of the frequency and number of TFH cells in lupus-prone mice. However, this inhibition has little effect on the production of T-cell-dependent antibodies following immunization with an exogenous antigen or on the frequency of virus-specific TFH cells induced by infection with influenza. In contrast, glutaminolysis inhibition reduces both immunization-induced and autoimmune TFH cells and humoral responses. Solute transporter gene signature suggests different glucose and amino acid fluxes between autoimmune TFH cells and exogenous antigen-specific TFH cells. Thus, blocking glucose metabolism may provide an effective therapeutic approach to treat systemic autoimmunity by eliminating autoreactive TFH cells while preserving protective immunity against pathogens

    Functional Maps of Protein Complexes from Quantitative Genetic Interaction Data

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    Recently, a number of advanced screening technologies have allowed for the comprehensive quantification of aggravating and alleviating genetic interactions among gene pairs. In parallel, TAP-MS studies (tandem affinity purification followed by mass spectroscopy) have been successful at identifying physical protein interactions that can indicate proteins participating in the same molecular complex. Here, we propose a method for the joint learning of protein complexes and their functional relationships by integration of quantitative genetic interactions and TAP-MS data. Using 3 independent benchmark datasets, we demonstrate that this method is >50% more accurate at identifying functionally related protein pairs than previous approaches. Application to genes involved in yeast chromosome organization identifies a functional map of 91 multimeric complexes, a number of which are novel or have been substantially expanded by addition of new subunits. Interestingly, we find that complexes that are enriched for aggravating genetic interactions (i.e., synthetic lethality) are more likely to contain essential genes, linking each of these interactions to an underlying mechanism. These results demonstrate the importance of both large-scale genetic and physical interaction data in mapping pathway architecture and function

    Microinjection Manipulation Resulted in the Increased Apoptosis of Spermatocytes in Testes from Intracytoplasmic Sperm Injection (ICSI) Derived Mice

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    The invention of intracytoplasmic sperm injection (ICSI) has possibly been the most important development in reproductive medicine, one that has given hope to thousands of infertile couples worldwide. However, concerns remain regarding the safety of this method since it is a more invasive procedure than in vitro fertilization (IVF), since a spermatozoon is injected into the oocyte cytoplasm. Using mice derived from IVF technology as a control, we assessed the influence of invasive microinjection in the process of transferring sperm into oocyte cytoplasm in ICSI procedure on the development and physiologic function of resultant offspring. Our results demonstrated that mice produced from ICSI and IVF had no significant difference in phenotypic indices including body weight, forelimb physiology, and learning and memory ability. However, increased spermatocyte apoptosis was observed in the testis of adult ICSI mice, when compared with IVF mice. And, decreased testis weight and marked damage of spermatogenic epithelia were found in aged ICSI mice. Furthermore, proteomic analysis verified that most of the differentiated proteins in testes between adult ICSI and IVF mice were those involved in regulation of apoptosis pathways. Our results demonstrated that the microinjection manipulation used in the ICSI procedure might pose potential risks to the fertility of male offspring. The changed expression of a series of proteins relating to apoptosis or proliferation might contribute to it. Further studies are necessary to better understand all the risks of ICSI

    Genetic Diversity and Linkage Disequilibrium in Chinese Bread Wheat (Triticum aestivum L.) Revealed by SSR Markers

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    Two hundred and fifty bread wheat lines, mainly Chinese mini core accessions, were assayed for polymorphism and linkage disequilibrium (LD) based on 512 whole-genome microsatellite loci representing a mean marker density of 5.1 cM. A total of 6,724 alleles ranging from 1 to 49 per locus were identified in all collections. The mean PIC value was 0.650, ranging from 0 to 0.965. Population structure and principal coordinate analysis revealed that landraces and modern varieties were two relatively independent genetic sub-groups. Landraces had a higher allelic diversity than modern varieties with respect to both genomes and chromosomes in terms of total number of alleles and allelic richness. 3,833 (57.0%) and 2,788 (41.5%) rare alleles with frequencies of <5% were found in the landrace and modern variety gene pools, respectively, indicating greater numbers of rare variants, or likely new alleles, in landraces. Analysis of molecular variance (AMOVA) showed that A genome had the largest genetic differentiation and D genome the lowest. In contrast to genetic diversity, modern varieties displayed a wider average LD decay across the whole genome for locus pairs with r2>0.05 (P<0.001) than the landraces. Mean LD decay distance for the landraces at the whole genome level was <5 cM, while a higher LD decay distance of 5–10 cM in modern varieties. LD decay distances were also somewhat different for each of the 21 chromosomes, being higher for most of the chromosomes in modern varieties (<5∼25 cM) compared to landraces (<5∼15 cM), presumably indicating the influences of domestication and breeding. This study facilitates predicting the marker density required to effectively associate genotypes with traits in Chinese wheat genetic resources
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