Single-cell sequencing (SCS) data have great potential in reconstructing the evolutionary history of tumors. Rapid advances in SCS technology in the past decade were followed by the design of various computational methods for inferring trees of tumor evolution. Some of the earliest methods were based on the direct search in the space of trees with the goal of finding the maximum likelihood tree. However, it can be shown that instead of searching directly in the tree space, we can perform a search in the space of binary matrices and obtain maximum likelihood tree directly from the maximum likelihood matrix. The potential of the latter tree search strategy has recently been recognized by different research groups and several related methods were published in the past 2 years. Here we provide a review of the theoretical background of these methods and a detailed discussion, which are largely missing in the available publications, of the correlation between the two tree search strategies. We also discuss each of the existing methods based on the search in the space of binary matrices and summarize the best-known single-cell DNA sequencing data sets, which can be used in the future for assessing performance on real data of newly developed methods.

The cyclic AMP pathway promotes melanocyte differentiation in part by triggering gene expression changes mediated by CREB and its coactivators (CRTC1-3). Differentiation is dysregulated in melanomas, although the contributions of different cAMP effectors in this setting is unclear. We report a selective differentiation impairment in CRTC3 KO melanocytes and melanoma cells, due to downregulation of OCA2 and block of melanosome maturation. CRTC3 stimulated OCA2 expression via binding to CREB on a conserved enhancer, a regulatory site for pigmentation and melanoma risk in humans. Response to cellular signaling differed between CRTC3 and its family members; CRTC3 was uniquely activated by ERK1/2-mediated phosphorylation at Ser391 and by low levels of cAMP. Phosphorylation at Ser391 was constitutively elevated in human melanoma cells with hyperactivated ERK1/2 signaling; knockout of CRTC3 in this setting impaired anchorage-independent growth, migration and invasiveness while CRTC3 overexpression supported cell survival in response to MAPK inhibition by vemurafenib. Human melanomas expressing gain of function mutations in CRTC3 were associated with poorer clinical outcome. Our results suggest that CRTC3 inhibition may provide benefit in the treatment of hyperpigmentation and melanoma, and potentially other disorders with deregulated cAMP/MAPK crosstalk.

The aim of study was to examine the effect of the boar ejaculate collection frequency on the parameters of its quality. The research covered a three-year period, and four most common boar breeds in our area. A total of 1705 ejaculates were taken from Yorkshire boars, 1693 ejaculates from Landrace boars, 1106 ejaculates from Pietrain boars and 669 ejaculates from Duroc boars. Within each breed, groups were formed according to the frequency of ejaculate taking (once, twice, three, four, five, or six times a month). Evaluation of ejaculate quality was performed in a reprocentre laboratory, according to their quality standards. Quality parameters that have been determined were the volume of ejaculate, sperm concentration, progressive sperm motility, live sperm count, the number of doses per ejaculate and the overall assessment of ejaculate. Results of this study show that the volume and progressive motility increase with the increase of frequency in ejaculate taking, while the sperm concentration drops, except for the Pietrain boars. The best results were observed in ejaculates collected 5-6 times during the month. The highest mean volume of ejaculate was found in the Landrace boars (292.22 ml), in ejaculate taking frequency of five times per month. The highest average progressive sperm motility was 92% in the Yorkshire boars, on collection frequency of six times a month, while the highest concentration of spermatozoa was found in the Duroc boars in collection frequency of one taking per month (447.32 mil/ml). The results of this study indicate that the frequency of ejaculate taking affects the boar semen quality parameters.

Metal chelators can be potentially employed in the treatment of various diseases, ranging from metal overload to neoplastic conditions. Some xanthene derivatives were previously reported to complex metals. Thus, in a search for a novel iron or copper chelator, a series of 9-(substituted phenyl)-2,6,7-trihydroxy-xanthene-3-ones was tested using a competitive spectrophotometric approach. The most promising compound was evaluated in biological models (breast adenocarcinoma cell lines and erythrocytes). In general, substitution of the benzene ring in position 9 had a relatively low effect on the chelation. Only the trifluoromethyl substitution resulted in stronger chelation, probably via a positive effect on solvation. All compounds chelated iron, but their copper-chelating effect was only minimal, since it was no longer observed under highly competitive conditions. Interestingly, all compounds reduced both iron and copper. Additional experiments showed that the trifluoromethyl derivative protected erythrocytes and even cancer cells against excess copper. In summary, the tested compounds are iron chelators, which are also capable of reducing iron/copper, but the copper-reducing effect is not associated with increased copper toxicity.

Quasi-asymptotic behavior of functions as a method has its application in observing many physical phenomena which are expressed by differential equations. The aim of the asymptotic method is to allow one to present the solution of a problem depending on the large (or small) parameter. One application of asymptotic methods in describing physical phenomena is the quasi-asymptotic approximation. The aim of this paper is to look at the quasi-asymptotic properties of multidimensional distributions by extracted variable. Distribution T(x0,x) from S'(Ṝ+1×Rn) has the property of the separability of variables, if it can be represented in form T(x0,x)=∑φi(x0)ψi (x) where distributions, φi(x0) from S'(Ṝ1) and ψi from S(Rn), x0 from Ṝ1+ and x is element Rn different values of do not depend on each other. Distribution T(x0,x) the element S'(Ṝ+1×Rn) is homogeneous and of order α at variable x0 is element Ṝ1+ and x=x1,x2,…,xn from Rn if for k>0 it applies that T(kx0,kx)=kα T(x0,x). The method of separating variables is one of the most widespread methods for solving linear differential equations in mathematical physics. In this paper, the results by V. S Vladimirov are used to present the proof of the basic theorems, regarding the quasi-asymptotic behavior of multidimensional distributions by a singular variable, with the application of quasi-asymptotics to the solution of differential equations.

In this paper, graded rings are $S$-graded rings inducing $S,$ that is, rings whose additive groups can be written as a direct sum of a family of their additive subgroups indexed by a nonempty set $S,$ and such that the product of two homogeneous elements is again a homogeneous element. As a generalization of the recently introduced notion of a $UJ$-ring, we define a graded $UJ$-ring. Graded nil clean rings which are graded $UJ$ are described. We also investigate the graded $UJ$-property under some graded ring constructions.

Este artigo tem como objetivo compreender quais os sentidos da panfletagem política na época de campanha para os sujeitos: que entregam e que recebem os panfletos. Pretende-se averiguar qual imagem que esses têm de política na atualidade e o que a panfletagem significa para eles. A pesquisa apoia-se nos estudos da Análise do Discurso materialista histórico, principalmente nas concepções da autora Eni Orlandi (2002, 2008, 2010). Sua materialidade é pesquisa qualitativa com entrevista semiestruturada envolvendo quatro posições sujeitos. Uma vez desenvolvido, esse trabalho possibilitou um entendimento do ato de panfletar no discurso político das eleições de 2018 no município de Tabaporã, estado de Mato Grosso, Brasil.

Previous research reported that corvids preferentially cache food in a location where no food will be available or cache more of a specific food in a location where this food will not be available. Here, we consider possible explanations for these prospective caching behaviours and directly compare two competing hypotheses. The Compensatory Caching Hypothesis suggests that birds learn to cache more of a particular food in places where that food was less frequently available in the past. In contrast, the Future Planning Hypothesis suggests that birds recall the ‘what–when–where’ features of specific past events to predict the future availability of food. We designed a protocol in which the two hypotheses predict different caching patterns across different caching locations such that the two explanations can be disambiguated. We formalised the hypotheses in a Bayesian model comparison and tested this protocol in two experiments with one of the previously tested species, namely Eurasian jays. Consistently across the two experiments, the observed caching pattern did not support either hypothesis; rather it was best explained by a uniform distribution of caches over the different caching locations. Future research is needed to gain more insight into the cognitive mechanism underpinning corvids’ caching for the future.