Intratumoral heterogeneity analysis reveals hidden associations between protein expression losses and patient survival in clear cell renal cell carcinoma.

Intratumoral heterogeneity (ITH) is a prominent feature of kidney cancer. It is not known whether it has utility in finding associations between protein expression and clinical parameters. We used ITH that is detected by immunohistochemistry (IHC) to aid the association analysis between the loss of SWI/SNF components and clinical parameters.160 ccRCC tumors (40 per tumor stage) were used to generate tissue microarray (TMA). Four foci from different regions of each tumor were selected. IHC was performed against PBRM1, ARID1A, SETD2, SMARCA4, and SMARCA2. Statistical analyses were performed to correlate biomarker losses with patho-clinical parameters. Categorical variables were compared between groups using Fisher\u27s exact tests. Univariate and multivariable analyses were used to correlate biomarker changes and patient survivals. Multivariable analyses were performed by constructing decision trees using the classification and regression trees (CART) methodology. IHC detected widespread ITH in ccRCC tumors. The statistical analysis of the Truncal loss (root loss) found additional correlations between biomarker losses and tumor stages than the traditional Loss in tumor (total) . Losses of SMARCA4 or SMARCA2 significantly improved prognosis for overall survival (OS). Losses of PBRM1, ARID1A or SETD2 had the opposite effect. Thus Truncal Loss analysis revealed hidden links between protein losses and patient survival in ccRCC

The stability of the spectator, Dirac, and Salpeter equations for mesons

Mesons are made of quark-antiquark pairs held together by the strong force. The one channel spectator, Dirac, and Salpeter equations can each be used to model this pairing. We look at cases where the relativistic kernel of these equations corresponds to a time-like vector exchange, a scalar exchange, or a linear combination of the two. Since the model used in this paper describes mesons which cannot decay physically, the equations must describe stable states. We find that this requirement is not always satisfied, and give a complete discussion of the conditions under which the various equations give unphysical, unstable solutions

Multiple tumor suppressors regulate a HIF-dependent negative feedback loop via ISGF3 in human clear cell renal cancer.

Whereas VHL inactivation is a primary event in clear cell renal cell carcinoma (ccRCC), the precise mechanism(s) of how this interacts with the secondary mutations in tumor suppressor genes, including PBRM1, KDM5C/JARID1C, SETD2, and/or BAP1, remains unclear. Gene expression analyses reveal that VHL, PBRM1, or KDM5C share a common regulation of interferon response expression signature. Loss of HIF2α, PBRM1, or KDM5C in VHL-/-cells reduces the expression of interferon stimulated gene factor 3 (ISGF3), a transcription factor that regulates the interferon signature. Moreover, loss of SETD2 or BAP1 also reduces the ISGF3 level. Finally, ISGF3 is strongly tumor-suppressive in a xenograft model as its loss significantly enhances tumor growth. Conversely, reactivation of ISGF3 retards tumor growth by PBRM1-deficient ccRCC cells. Thus after VHL inactivation, HIF induces ISGF3, which is reversed by the loss of secondary tumor suppressors, suggesting that this is a key negative feedback loop in ccRCC. © 2018, Liao et al

PBRM1 acts as a p53 lysine-acetylation reader to suppress renal tumor growth.

p53 acetylation is indispensable for its transcriptional activity and tumor suppressive function. However, the identity of reader protein(s) for p53 acetylation remains elusive. PBRM1, the second most highly mutated tumor suppressor gene in kidney cancer, encodes PBRM1. Here, we identify PBRM1 as a reader for p53 acetylation on lysine 382 (K382Ac) through its bromodomain 4 (BD4). Notably, mutations on key residues of BD4 disrupt recognition of p53 K382Ac. The mutation in BD4 also reduces p53 binding to promoters of target genes such as CDKN1A (p21). Consequently, the PBRM1 BD4 mutant fails to fully support p53 transcriptional activity and is defective as a tumor suppressor. We also find that expressions of PBRM1 and p21 correlate with each other in human kidney cancer samples. Our findings uncover a tumor suppressive mechanism of PBRM1 in kidney cancer and provide a mechanistic insight into the crosstalk between p53 and SWI/SNF complexes

Особенности и закономерности изменения восстановлености углей башкирского яруса Западного Донбасса

В статье приведена детальная петрографическая характеристика углей башкирского яруса Западного Донбасса. Проведена классификация по восстановлености в соответствии с петрографическими типами. Установлены стратиграфические и площадные закономерности изменения степени восстановлености.У статті наведена детальна петрографічна характеристика вугілля башкирського ярусу Західного Донбасу. Проведена класифікація відновленості, згідно з петрографічними типами. Встановлені стратиграфічні та просторові закономірності зміни ступеню відновленості.The article gives detailed petrographic characteristics of coal of Bashkirian formation of Western Donbas. The classifications for recovery in accordance with petrographic types are given. The stratigraphic and areal patterns of change in the degree of recovery are established

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

Genetic analysis for sooty mold resistance and heart of palm yield in Archontophoenix.

Palmeiras do gênero Archontophoenix, utilizadas tanto como ornamentais quanto produtoras de palmito de qualidade, são susceptíveis à fumagina, doença associada à infestação por pulgões, que afeta a fotossíntese, o crescimento e a aparência das plantas. Foram avaliados a campo a resistência à fumagina conjuntamente com três caracteres associados ao crescimento em 24 famílias de meios-irmãos, 28 meses após o plantio, a fim de identificar a variabilidade genética para os caracteres resistência à fumagina, altura, diâmetro e número de folhas; estimar as correlações genotípicas e fenotípicas envolvendo esses quatro caracteres; e aplicar a estratégia de seleção usando o índice multiefeitos. Houve diferenças entre as famílias para os caracteres avaliados, sugerindo a possibilidade de seleção. O baixo coeficiente de variação observado para resistência à fumagina (9,48%) indica que o método de avaliação adotado, baseado em escala de notas após observação visual, foi eficiente e prático para comparar níveis de infestação do complexo fungo+pulgão em palmeiras do gênero Archontophoenix. As estimativas da herdabilidade no sentido restrito foram baixas a médias para os caracteres relacionados ao crescimento (0,10, 0,26 e 0,26 para número de folhas, diâmetro e altura da planta, respectivamente) e muito altas (0,91) para resistência à fumagina. Correlação genética positiva foi observada entre resistência à fumagina e altura da planta, indicando que a eliminação de plantas muito susceptíveis pode ser feita sem interferência na seleção indireta para produção de palmito. A estratégia de seleção pelo índice multiefeitos (com ganhos genéticos esperados variando de 6,23 a 11,83%) mostrou-se adequada para melhorar simultaneamente caracteres relacionados ao crescimento e à produção de palmito