Alexander Moiseev  Ludmila Snopova  Sergey Kuznetsov  Natalia Buyanova  Vadim Elagin  Marina Sirotkina  Elena Kiseleva  Lev Matveev  Vladimir Zaitsev  Felix Feldchtein  Elena Zagaynova  Valentin Gelikonov  Natalia Gladkova  Alex Vitkin  Grigory Gelikonov 《Journal of biophotonics》2018,11(4)

A novel machine‐learning method to distinguish between tumor and normal tissue in optical coherence tomography (OCT) has been developed. Pre‐clinical murine ear model implanted with mouse colon carcinoma CT‐26 was used. Structural‐image‐based feature sets were defined for each pixel and machine learning classifiers were trained using “ground truth” OCT images manually segmented by comparison with histology. The accuracy of the OCT tumor segmentation method was then quantified by comparing with fluorescence imaging of tumors expressing genetically encoded fluorescent protein KillerRed that clearly delineates tumor borders. Because the resultant 3D tumor/normal structural maps are inherently co‐registered with OCT derived maps of tissue microvasculature, the latter can be color coded as belonging to either tumor or normal tissue. Applications to radiomics‐based multimodal OCT analysis are envisioned.   相似文献   

    

Susanne Klein-Scory  Marina Maslova  Michael Pohl  Christina Eilert-Micus  Roland Schroers  Wolff Schmiegel  Alexander Baraniskin 《Translational oncology》2018,11(2):213-220

PURPOSE: Despite therapeutic improvements, all patients with nonresectable metastatic colorectal cancer (mCRC) acquire resistance to treatment probably due to the growth of mutated clones. In contrast to tissue-based studies, liquid biopsies have enabled the opportunity to reveal emerging resistance to treatment by detecting mutated clones and noninvasively monitoring clonal dynamics during therapy. METHODS: The courses of three patients with mCRC who were initially RAS wild-type were monitored longitudinally using liquid biopsy with long-term follow-up of up to 20 sequential samples. Detection of fragmented RAS mutated circulating cell-free DNA (cf)DNA in plasma was performed by BEAMing. In addition, plasma digital droplet PCR was used to detect and quantify BRAF and PIK3CA mutated cfDNA. Changes of mutational load were correlated with imaging data. RESULTS: A combination of liquid biopsy and radiological imaging enabled visualization of the occurrence of clonal redistribution after discontinuation of anti-EGFR mAb therapy, as well as emerging RAS mutations during therapy with anti-EGFR mAb indicating resistance. Furthermore, we found that growth of RAS mutated clones is independent of direct selective pressure by anti-EGFR therapy, which is a significant and new finding of this study. CONCLUSIONS: Our findings demonstrated the whole spectrum of clonal selection and redistribution of mutated cell clones leading to acquired resistance. Given our observation that the growth of RAS mutated clones can evolve even in the absence of anti-EGFR mAb therapy, there is a clear imperative to monitor RAS mutations in serial blood draws in all RAS wild-type patients in general and independent of the therapy.  相似文献   

    

Maria Caroline Alves Coelho  Marina Lipkin Vasquez  Luiz Eduardo Wildemberg  Mari C. Vázquez‐Borrego  Luciana Bitana  Aline Helen da Silva Camacho  Débora Silva  Liana Lumi Ogino  Nina Ventura  Leila Chimelli  Raul M. Luque  Leandro Kasuki  Mônica R. Gadelha 《Journal of cellular and molecular medicine》2018,22(4):2110-2116

β‐arrestins seem to have a role in endocytosis and desensitization of somatostatin receptor subtype 2 (sst2) and could be associated with the responsiveness to somatostatin receptor ligands (SRL) in patients with acromegaly. To investigate the in vivo correlation between β‐arrestins 1 and 2 with sst2, sst5 and dopamine receptor subtype 2 (D2) expressions, and the association of β‐arrestins with response to first‐generation SRL and invasiveness in somatotropinomas. β‐arrestins 1 and 2, sst2, sst5 and D2 mRNA expressions were evaluated by quantitative real‐time RT‐PCR on tumoral tissue of 96 patients. Moreover, sst2 and sst5 protein expressions were also evaluated in 40 somatotropinomas by immunohistochemistry. Response to SRL, defined as GH <1 μg/l and normal IGF‐I levels, was assessed in 40 patients. The Knosp‐Steiner criteria were used to define invasiveness. Median β‐arrestin 1, β‐arrestin 2, sst2, sst5 and D2 mRNA copy numbers were 478; 9375; 731; 156 ; and 3989, respectively. There was a positive correlation between β‐arrestins 1 and 2 (R = 0.444, P < 0.001). However, no correlation between β‐arrestins and sst2, sst5 (mRNA and protein levels) or D2 was found. No association was found between β‐arrestins expression and SRL responsiveness or tumour invasiveness. Although previous data suggest a putative correlation between β‐arrestins and sst2, our data clearly indicated that no association existed between β‐arrestins and sst2, sst5 or D2 expression, nor with response to SRL or tumour invasiveness. Therefore, further studies are required to clarify whether β‐arrestins have a role in the response to treatment with SRL in acromegaly.  相似文献   

    

Antonio Profico  Stefan Schlager  Veronica Valoriani  Costantino Buzi  Marina Melchionna  Alessio Veneziano  Pasquale Raia  Jacopo Moggi‐Cecchi  Giorgio Manzi 《American journal of physical anthropology》2018,166(4):979-986

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Marina Harvey  Michelle Power  Michael Wilson 《Journal of biological education》2017,51(3):315-325

One response to the global trend of increasing rates of student participation in tertiary education has been for universities to increase the number of intensive mode of delivery subjects available. This phenomenon extends to science subjects. Embarking on offering an undergraduate science subject in intensive mode for the first time at the Australian case example university, it was essential to first learn about good pedagogical design and practice from other educational organisations. To achieve this, a website audit of Australian universities was undertaken in tandem with a critical review of the Australian and international literature on intensive mode of delivery. While it was found that a majority of Australian universities offer science subjects in intensive mode, these subjects were primarily at the postgraduate level of study. The literature focusing on intensive mode in science was minimal. It revealed definitional ambiguity and conceptual non-uniformity as well as a range of positive, negative and inconclusive results in relation to the academic and ‘real-world’ outcomes of intensive mode. This review identifies a need for evidenced-based empirical research into the pedagogy around intensive mode for undergraduate science subjects.  相似文献   

    

Ashwani Kumar Tiwari  Marina De Maio 《人类与生态风险评估》2017,23(5):1153-1163

The aim of this study is to assess the risk to human health presented by total chromium (Cr_T) and hexavalent chromium (Cr(VI)) due to the intake of the groundwater (shallow aquifer) in the Aosta Valley region. One hundred and fifty-three groundwater samples were collected from seventeen locations in the Aosta Valley region during the years 2007–2015 to determine the Cr_T and Cr(VI) concentrations. The cancer risk (CR) and non-cancer risk, reflected by the hazard quotient (HQ) were estimated using the United States Environmental Protection Agency methods. The concentrations of Cr_T exceeded the limit for drinking water established by Italian legislative decree at the sampling location Ao23 in all the years studied. Moreover, Cr(VI) concentrations exceeded the limit for drinking water at many sampling locations in the study area. The estimated HQ values for non-cancer risk suggested that all the sampling locations were well within the safe zone during all the years except for location Ao23 in many years considered. The CR levels were very low to high risk in the groundwater of the study area. The results of this analysis suggest that a suitable treatment of the groundwater is required before its utilization for drinking purposes. This study could be of great value for the prevention of risk to human health and for groundwater resource management.  相似文献   

    

Laurene Pecuchet  Martin Lindegren  Manuel Hidalgo  Marina Delgado  Antonio Esteban  Heino O. Fock  Luis Gil de Sola  Antonio Punzón  Jón Sólmundsson  Mark R. Payne 《Global Ecology and Biogeography》2017,26(7):812-822

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Viviana Anelli  Marina Mione 《Pigment cell & melanoma research》2017,30(1):8-10

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Jennie O' Loughlin;Kirill Zinovjev;Silvia Napolitano;Marc van der Kamp;Marina Rubini; 《Protein science : a publication of the Protein Society》2024,33(2):e4877

The cis/trans isomerization of peptidyl-prolyl peptide bonds is often the bottleneck of the refolding reaction for proteins containing cis proline residues in the native state. Proline (Pro) analogues, especially C4-substituted fluoroprolines, have been widely used in protein engineering to enhance the thermodynamic stability of peptides and proteins and to investigate folding kinetics. 4-thiaproline (Thp) has been shown to bias the ring pucker of Pro, to increase the cis population percentage of model peptides in comparison to Pro, and to diminish the activation energy barrier for the cis/trans isomerization reaction. Despite its intriguing properties, Thp has been seldom incorporated into proteins. Moreover, the impact of Thp on the folding kinetics of globular proteins has never been reported. In this study, we show that upon incorporation of Thp at cisPro76 into the thioredoxin variant Trx1P the half-life of the refolding reaction decreased from ~2 h to ~35 s. A dramatic acceleration of the refolding rate could be observed also for the protein pseudo wild-type barstar upon replacement of cisPro48 with Thp. Quantum chemical calculations suggested that the replacement of the CγH2 group by a sulfur atom in the pyrrolidine ring, might lower the barrier for cis/trans rotation due to a weakened peptide bond. The protein variants retained their thermodynamic stability upon incorporation of Thp, while the catalytic and enzymatic activities of the modified Trx1P remained unchanged. Our results show that the Pro isostere Thp might accelerate the rate of the slow refolding reaction for proteins containing cis proline residues in the native state, independent from the local structural environment.  相似文献   

    

Alida Frankline Hasiniaina  Ute Radespiel  Sharon E. Kessler  Mamy Rina Evasoa  Solofonirina Rasoloharijaona  Blanchard Randrianambinina  Elke Zimmermann  Sabine Schmidt  Marina Scheumann 《Ecology and evolution》2020,10(8):3784-3797

Acoustic phenotypic variation is of major importance for speciation and the evolution of species diversity. Whereas selective and stochastic forces shaping the acoustic divergence of signaling systems are well studied in insects, frogs, and birds, knowledge on the processes driving acoustic phenotypic evolution in mammals is limited. We quantified the acoustic variation of a call type exchanged during agonistic encounters across eight distinct species of the smallest‐bodied nocturnal primate radiation, the Malagasy mouse lemurs. The species live in two different habitats (dry forest vs. humid forest), differ in geographic distance to each other, and belong to four distinct phylogenetic clades within the genus. Genetically defined species were discriminated reliably on the phenotypic level based on their acoustic distinctiveness in a discriminant function analysis. Acoustic variation was explained by genetic distance, whereas differences in morphology, forest type, or geographic distance had no effect. The strong impact of genetics was supported by a correlation between acoustic and genetic distance and the high agreement in branching pattern between the acoustic and molecular phylogenetic trees. In sum, stochastic factors such as genetic drift best explained acoustic diversification in a social communication call of mouse lemurs.  相似文献