G-quadruplex formation in human telomeric (TTAGGG)4 sequence with complementary strand in close vicinity under molecularly crowded condition

Chromosomes in vertebrates are protected at both ends by telomere DNA composed of tandem (TTAGGG)n repeats. DNA replication produces a blunt-ended leading strand telomere and a lagging strand telomere carrying a single-stranded G-rich overhang at its end. The G-rich strand can form G-quadruplex structure in the presence of K+ or Na+. At present, it is not clear whether quadruplex can form in the double-stranded telomere region where the two complementary strands are constrained in close vicinity and quadruplex formation, if possible, has to compete with the formation of the conventional Watson–Crick duplex. In this work, we studied quadruplex formation in oligonucleotides and double-stranded DNA containing both the G- and C-rich sequences to better mimic the in vivo situation. Under such competitive condition only duplex was observed in dilute solution containing physiological concentration of K+. However, quadruplex could preferentially form and dominate over duplex structure under molecular crowding condition created by PEG as a result of significant quadruplex stabilization and duplex destabilization. This observation suggests quadruplex may potentially form or be induced at the blunt end of a telomere, which may present a possible alternative form of structures at telomere ends

A reactive oxygen species–related signature to predict prognosis and aid immunotherapy in clear cell renal cell carcinoma

BackgroundClear cell renal cell carcinoma (ccRCC) is a malignant disease containing tumor-infiltrating lymphocytes. Reactive oxygen species (ROS) are present in the tumor microenvironment and are strongly associated with cancer development. Nevertheless, the role of ROS-related genes in ccRCC remains unclear.MethodsWe describe the expression patterns of ROS-related genes in ccRCC from The Cancer Genome Atlas and their alterations in genetics and transcription. An ROS-related gene signature was constructed and verified in three datasets and immunohistochemical staining (IHC) analysis. The immune characteristics of the two risk groups divided by the signature were clarified. The sensitivity to immunotherapy and targeted therapy was investigated.ResultsOur signature was constructed on the basis of glutamate-cysteine ligase modifier subunit (GCLM), interaction protein for cytohesin exchange factors 1 (ICEF1), methionine sulfoxide reductase A (MsrA), and strawberry notch homolog 2 (SBNO2) genes. More importantly, protein expression levels of GCLM, MsrA, and SBNO2 were detected by IHC in our own ccRCC samples. The high-risk group of patients with ccRCC suffered lower overall survival rates. As an independent predictor of prognosis, our signature exhibited a strong association with clinicopathological features. An accurate nomogram for improving the clinical applicability of our signature was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the signature was closely related to immune response, immune activation, and immune pathways. The comprehensive results revealed that the high-risk group was associated with high infiltration of regulatory T cells and CD8+ T cells and more benefited from targeted therapy. In addition, immunotherapy had better therapeutic effects in the high-risk group.ConclusionOur signature paved the way for assessing prognosis and developing more effective strategies of immunotherapy and targeted therapy in ccRCC

Y chromosome evidence of earliest modern human settlement in East Asia and multiple origins of Tibetan and Japanese populations

<p>Abstract</p> <p>Background</p> <p>The phylogeography of the Y chromosome in Asia previously suggested that modern humans of African origin initially settled in mainland southern East Asia, and about 25,000–30,000 years ago, migrated northward, spreading throughout East Asia. However, the fragmented distribution of one East Asian specific Y chromosome lineage (D-M174), which is found at high frequencies only in Tibet, Japan and the Andaman Islands, is inconsistent with this scenario.</p> <p>Results</p> <p>In this study, we collected more than 5,000 male samples from 73 East Asian populations and reconstructed the phylogeography of the D-M174 lineage. Our results suggest that D-M174 represents an extremely ancient lineage of modern humans in East Asia, and a deep divergence was observed between northern and southern populations.</p> <p>Conclusion</p> <p>We proposed that D-M174 has a southern origin and its northward expansion occurred about 60,000 years ago, predating the northward migration of other major East Asian lineages. The Neolithic expansion of Han culture and the last glacial maximum are likely the key factors leading to the current relic distribution of D-M174 in East Asia. The Tibetan and Japanese populations are the admixture of two ancient populations represented by two major East Asian specific Y chromosome lineages, the O and D haplogroups.</p

Probing the Isospin Dependent In-Medium Nucleon-Nucleon Cross Section by Nucleon Emissions

The effects of the symmetry potential and the isospin dependent in-medium nucleon-nucleon (NN) cross section on the number of proton(neutron) emissions N$_p(N_n$) are studied respectively within an isospin-dependent quantum molecular dynamics (IQMD) model. The isospin dependent in-medium NN cross section is found to have a strong influence on N$_p(N_n$) but N$_p(N_n$) is not sensitive to the symmetry potential for the neutron-deficient colliding system at relatively high energies.We propose to make use of the N$_p(N_n$) as a probe to extract information on the isospin dependent in-medium NN cross section.Comment: 7 pages,3 figure

Systematic biases in determining dust attenuation curves through galaxy SED fitting

While the slope of the dust attenuation curve ($\delta$) is found to correlate with effective dust attenuation ($A_V$) as obtained through spectral energy distribution (SED) fitting, it remains unknown how the fitting degeneracies shape this relation. We examine the degeneracy effects by fitting SEDs of a sample of local star-forming galaxies (SFGs) selected from the Galaxy And Mass Assembly survey, in conjunction with mock galaxy SEDs of known attenuation parameters. A well-designed declining starburst star formation history is adopted to generate model SED templates with intrinsic UV slope ($\beta_0$) spanning over a reasonably wide range. The best-fitting $\beta_0$ for our sample SFGs shows a wide coverage, dramatically differing from the limited range of $\beta_0<-2.2$ for a starburst of constant star formation. Our results show that strong degeneracies between $\beta_0$, $\delta$, and $A_V$ in the SED fitting induce systematic biases leading to a false $A_V$--$\delta$ correlation. Our simulation tests reveal that this relationship can be well reproduced even when a flat $A_V$--$\delta$ relation is taken to build the input model galaxy SEDs. The variations in best-fitting $\delta$ are dominated by the fitting errors. We show that assuming a starburst with constant star formation in SED fitting will result in a steeper attenuation curve, smaller degeneracy errors, and a stronger $A_V$--$\delta$ relation. Our findings confirm that the $A_V$--$\delta$ relation obtained through SED fitting is likely driven by the systematic biases induced by the fitting degeneracies between $\beta_0$, $\delta$, and $A_V$.Comment: 21 pages, 13 figures, accepted for publication in the MNRAS, Comments welcome