Gaia as Solaris: An Alternative Default Evolutionary Trajectory

Now that we know that Earth-like planets are ubiquitous in the universe, as well as that most of them are much older than the Earth, it is justified to ask to what extent evolutionary outcomes on other such planets are similar, or indeed commensurable, to the outcomes we perceive around us. In order to assess the degree of specialty or mediocrity of our trajectory of biospheric evolution, we need to take into account recent advances in theoretical astrobiology, in particular (i) establishing the history of habitable planets' formation in the Galaxy, and (ii) understanding the crucial importance of "Gaian" feedback loops and temporal windows for the interaction of early life with its physical environment. Hereby we consider an alternative macroevolutionary pathway that may result in tight functional integration of all sub-planetary ecosystems, eventually giving rise to a true superorganism at the biospheric level. The blueprint for a possible outcome of this scenario has been masterfully provided by the great Polish novelist Stanisław Lem in his 1961 novel Solaris. In fact, Solaris offers such a persuasive and powerful case for an "extremely strong" Gaia hypothesis that it is, arguably, high time to investigate it in a discursive astrobiological and philosophical context. In addition to novel predictions in the domain of potentially detectable biosignatures, some additional cognitive and heuristic benefits of studying such extreme cases of functional integration are briefly discussed

Wilms tumor (wt)1 gene expression in children with acute leukemia in Serbia

Acute leukemias constitute the most common malignancy in childhood, accounting for 25-35% of all cancer in children. They are divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Genetic susceptibility is known to play a major role in childhood leukemias. Wilms tumor (WT)1 is a zinc finger transcription factor involved in regulating the process of cell differentiation; it has been implicated in a wide range of human neoplasms. WT1 overexpression in the bone marrow at diagnosis is reported to be an independent negative prognostic factor in adults and children with AML. The aim of the present investigation was to determine the expression of WT1 in the bone marrow of children with AML and ALL in Serbia and its possible impact on patient survival. We determined bone marrow WT1 expression levels by reverse -transcription polymerase chain reaction (RT-PCR) at diagnosis in 20 children with AML and 20 children with ALL (16 B-ALL and 4 T-ALL), as well as 15 age- and sex-matched controls who were evaluated for immune thrombocytopenic purpura (ITP). For children with AML, follow-up samples were also analyzed one month after treatment initiation and at variable later timepoints of control punctures. The results were normalized based on WT1 expression in controls. We found that children with AML had significantly higher WT1 expression at diagnosis (median SD: 139.42 244.03) than those with ALL (1.18 54.37; Mann -Whitney U=82; p lt 0.01) and ITP (0.76 1.01; U=32; p lt 0.01). Patients with T-ALL had higher WT1 expression than those with B-ALL, though significance was not reached due to subgroup size; differences between AML subgroups according to the French-American-British (FAB) classification were also below the level of significance, though a tendency toward higher values in M3 and M4 leukemias was notable. There was also a tendency toward higher values in 14 children with AML who were still alive after a median follow-up of 1.5 years (181.42 192.52) than in 6 who succumbed to the disease (104.29 354.87). All children with AML who had WT1 expression 1 month after diagnosis below the fourth quartile (10 of 10) were still alive, while only 2 of 5 with 1 -month WT1 expression in the fourth quartile survived (Fisher's exact test: p=0.0952). Taken together, our results support a role for WT1 in the diagnostic workup in children with acute leukemia, although it needs to be considered in view of a complex and indvidualized context

Parallel targeted next generation sequencing of childhood and adult acute myeloid leukemia patients reveals uniform genomic profile of the disease

The age-specific differences in the genetic mechanisms of myeloid leukemogenesis have been observed and studied previously. However, NGS technology has provided a possibility to obtain a large amount of mutation data. We analyzed DNA samples from 20 childhood (cAML) and 20 adult AML (aAML) patients, using NGS targeted sequencing. The average coverage of high-quality sequences was 2981 x per amplicon. A total of 412 (207 cAML, 205 aAML) variants in the coding regions were detected; out of which, only 122 (62 cAML and 60 aAML) were potentially protein-changing. Our results confirmed that AML contains small number of genetic alterations (median 3 mutations/patient in both groups). The prevalence of the most frequent single gene AML associated mutations differed in cAML and aAML patient cohorts: IDH1 (0 % cAML, 5 % aAML), IDH2 (0 % cAML, 10 % aAML), NPM1 (10 % cAML, 35 % aAML). Additionally, potentially protein-changing variants were found in tyrosine kinase genes or genes encoding tyrosine kinase associated proteins (JAK3, ABL1, GNAQ, and EGFR) in cAML, while among aAML, the prevalence is directed towards variants in the methylation and histone modifying genes (IDH1, IDH2, and SMARCB1). Besides uniform genomic profile of AML, specific genetic characteristic was exclusively detected in cAML and aAML

Gaia as Solaris: An Alternative Default Evolutionary Trajectory

Now that we know that Earth-like planets are ubiquitous in the universe, as well as that most of them are much older than the Earth, it is justified to ask to what extent evolutionary outcomes on other such planets are similar, or indeed commensurable, to the outcomes we perceive around us. In order to assess the degree of specialty or mediocrity of our trajectory of biospheric evolution, we need to take into account recent advances in theoretical astrobiology, in particular (i) establishing the history of habitable planets' formation in the Galaxy, and (ii) understanding the crucial importance of "Gaian" feedback loops and temporal windows for the interaction of early life with its physical environment. Hereby we consider an alternative macroevolutionary pathway that may result in tight functional integration of all sub-planetary ecosystems, eventually giving rise to a true superorganism at the biospheric level. The blueprint for a possible outcome of this scenario has been masterfully provided by the great Polish novelist Stanis{\l}aw Lem in his 1961 novel Solaris. In fact, Solaris offers such a persuasive and powerful case for an "extremely strong" Gaia hypothesis that it is, arguably, high time to investigate it in a discursive astrobiological and philosophical context. In addition to novel predictions in the domain of potentially detectable biosignatures, some additional cognitive and heuristic benefits of studying such extreme cases of functional integration are briefly discussed.Comment: 20 pages, 1 figure; accepted in "Origins of Life and Evolution of Biospheres

Lipopolysaccharide can modify differentiation and immunomodulatory potential of periodontal ligament stem cells via ERK1,2 signaling

Lipopolysaccharide (LPS) is a pertinent deleterious factor in oral microenvironment for cells which are carriers of regenerative processes. The aim of this study was to investigate the emerging in vitro effects of LPS (Escherichia coli) on human periodontal ligament stem cell (PDLSC) functions and associated signaling pathways. We demonstrated that LPS did not affect immunophenotype, proliferation, viability, and cell cycle of PDLSCs. However, LPS modified lineage commitment of PDLSCs inhibiting osteogenesis by downregulating Runx2, ALP, and Ocn mRNA expression, while stimulating chondrogenesis and adipogenesis by upregulating Sox9 and PPAR mRNA expression. LPS promoted myofibroblast-like phenotype of PDLSCs, since it significantly enhanced PDLSC contractility, as well as protein and/or gene expression of TGF-beta, fibronectin (FN), alpha-SMA, and NG2. LPS also increased protein and gene expression levels of anti-inflammatory COX-2 and pro-inflammatory IL-6 molecules in PDLSCs. Inhibition of peripheral blood mononuclear cells (MNCs) transendothelial migration in presence of LPS-treated PDLSCs was accompanied by the reduction of CD29 expression within MNCs. However, LPS treatment did not change the inhibitory effect of PDLSCs on mitogen-stimulated proliferation of CD4(+) and the ratio of CD4(+)CD25(high)/CD4(+)CD25(low) lymphocytes. LPS-treated PDLSCs did not change the frequency of CD34(+) and CD45(+) cells, but decreased the frequency of CD33(+) and CD14(+) myeloid cells within MNCs. Moreover, LPS treatment attenuated the stimulatory effect of PDLSCs on CFC activity of MNCs, predominantly the CFU-GM number. The results indicated that LPS-activated ERK1,2 was at least partly involved in the observed effects on PDLSC differentiation capacity, acquisition of myofibroblastic attributes, and changes of their immunomodulatory features