A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms

We describe a genetic variation map for the chicken genome containing 2.8 million single-nucleotide polymorphisms ( SNPs). This map is based on a comparison of the sequences of three domestic chicken breeds ( a broiler, a layer and a Chinese silkie) with that of their wild ancestor, red jungle fowl. Subsequent experiments indicate that at least 90% of the variant sites are true SNPs, and at least 70% are common SNPs that segregate in many domestic breeds. Mean nucleotide diversity is about five SNPs per kilobase for almost every possible comparison between red jungle fowl and domestic lines, between two different domestic lines, and within domestic lines - in contrast to the notion that domestic animals are highly inbred relative to their wild ancestors. In fact, most of the SNPs originated before domestication, and there is little evidence of selective sweeps for adaptive alleles on length scales greater than 100 kilobases

The Genomes of Oryza sativa: A History of Duplications

We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000–40,000. Only 2%–3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The General Traveling Wave Solutions of the Fisher Equation with Degree Three

We employ the complex method to research the integrality of the Fisher equations with degree three. We obtain the sufficient and necessary condition of the integrable of the Fisher equations with degree three and the general meromorphic solutions of the integrable Fisher equations with degree three, which improves the corresponding results obtained by Feng and Li (2006), Guo and Chen (1991), and Ağırseven and Öziş (2010). Moreover, all wg,1(z) are new general meromorphic solutions of the Fisher equations with degree three for c=±3/2. Our results show that the complex method provides a powerful mathematical tool for solving a large number of nonlinear partial differential equations in mathematical physics

An Estimation of Radiobiological Parameters for Head-and-Neck Cancer Cells and the Clinical Implications.

In vitro survival measurements using two human head-and-neck cancer (HNC) cell lines were performed. The specially designed split-dose surviving fraction was obtained and fitted to the linear-quadratic formalism. The repair halftime (Tr), the potential doubling time (Td), a/β and radiosensitivity a, were estimated. Other radiobiological models: EUD, BED, TCP, etc., were used to examine the potential treatment effectiveness of different IMRT techniques. Our data indicated the repair halftime of ~17 min based on two HNC cell lines. The combined a/β, a and Td are a/β = 8.1 ± 4.1 Gy, a = 0.22 ± 0.08 Gy-1, Td = 4.0 ± 1.8 day, respectively. The prolonged IMRT dose delivery for entire HNC treatment course could possibly result in the loss of biological effectiveness, i.e., the target EUDs decreased by 11% with fraction dose delivery time varying from 5 to 30 min. We determined the sublethal damage repair halftime and other radiobiological parameters for HNC cells, and to evaluate treatment effectiveness of the prolonged dose delivery times associated with different IMRT techniques. The estimated repair halftime for HNC is relatively short and may be comparable to the step-and-shoot IMRT fraction dose delivery time. The effectiveness of IMRT treatment may be improved by reducing the fraction delivery time for HNC treatment

An Estimation of Radiobiological Parameters for Head-and-Neck Cancer Cells and the Clinical Implications

<em>In vitro</em> survival measurements using two human head-and-neck cancer (HNC) cell lines were performed. The specially designed split-dose surviving fraction was obtained and fitted to the linear-quadratic formalism. The repair halftime (Tr), the potential doubling time (T<sub>d</sub>), a/β and radiosensitivity a, were estimated. Other radiobiological models: EUD, BED, TCP, <em>etc</em>., were used to examine the potential treatment effectiveness of different IMRT techniques. Our data indicated the repair halftime of ~17 min based on two HNC cell lines. The combined a/β, a and T<sub>d</sub> are a/β = 8.1 ± 4.1 Gy, a = 0.22 ± 0.08 Gy<sup>−1</sup>, T<sub>d</sub> = 4.0 ± 1.8 day, respectively. The prolonged IMRT dose delivery for entire HNC treatment course could possibly result in the loss of biological effectiveness, <em>i.e</em>., the target EUDs decreased by 11% with fraction dose delivery time varying from 5 to 30 min. We determined the sublethal damage repair halftime and other radiobiological parameters for HNC cells, and to evaluate treatment effectiveness of the prolonged dose delivery times associated with different IMRT techniques. The estimated repair halftime for HNC is relatively short and may be comparable to the step-and-shoot IMRT fraction dose delivery time. The effectiveness of IMRT treatment may be improved by reducing the fraction delivery time for HNC treatment

m6A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK

The N6-methyladenosine (m6A) RNA modification can regulate autophagy to modulate the growth and development of tumors, but the mechanism of m6A modification for the regulation of autophagy in hepatocellular carcinoma cells (HCC) remains unclear. In the study, the knockdown of the Wilms’ tumor 1-associating protein (WTAP) was made in HCC to study the correlation between m6A modification and autophagy. A fluorescent confocal microscopy analysis showed that the knockdown of WTAP could facilitate the autophagy of HCC. A Western blot analysis showed that the level of p-AMPK was decreased in WTAP-knockdown HCC cells. Additionally, LKB1, the upstream kinase of AMPK, was regulated by WTAP and it could mediate the phosphorylation of AMPK in an m6A-dependent manner. Further studies revealed that the knockdown of WTAP could reduce the level of LKB1 mRNA with m6A. This could result in the increased stability of LKB1 mRNA to promote its expression. The knockdown of WTAP could upregulate the level of autophagy and inhibit HCC proliferation. However, the overexpression of WTAP could resist autophagic cell death

Correction: Li et al. m⁶A mRNA Methylation Regulates LKB1 to Promote Autophagy of Hepatoblastoma Cells through Upregulated Phosphorylation of AMPK. <i>Genes</i> 2021, <i>12</i>, 1747

In the original publication [...

Knockdown of NRAGE induces odontogenic differentiation by activating NF-κB signaling in mouse odontoblast-like cells

<p><b>Purpose</b>: Neurotrophin receptor-interacting MAGE homologue (Nrage) plays an important role in bone development and the metabolism of normal skeletal structures. Our previous study showed that Nrage inhibited the odontogenic differentiation of mouse dental pulp cells. However, the potential roles and mechanism of Nrage in regulating odontogenic differentiation are unknown. The aim of this study was to investigate the molecular mechanism of Nrage in odontogenic differentiation of mouse odontoblast-like cells.</p> <p><b>Materials and methods</b>: Endogenous expression of Nrage was stably downregulated by lentivirus-mediated shRNA. Mineralized nodules formation was detected by alizarin red S staining. Dmp-1, Dspp, and ALP mRNA and protein levels were detected by qRT-PCR and western blotting, respectively. In addition, ALPase activity was detected. Confocal microscopy and co-immunoprecipitation (co-IP) were used to analyze the interactions between NRAGE and NF-κB signaling molecules. An IKK inhibitor was also used in the study.</p> <p><b>Results</b>: NRAGE expression in odontoblasts was downregulated during mouse first maxillary molar development. Moreover, NRAGE expression was downregulated during odontogenic differentiation of odontoblast-like cells. NRAGE knockdown significantly upregulated DMP1 and DSP expression, increased ALPase activity, and promoted mineralized nodule formation. In addition, NRAGE knockdown increased the translocation of NF-κB1 to the nucleus and phosphorylation levels of p65. Co-IP results showed that NRAGE bound to IKKβ. Most importantly, the promoting effect of Nrage knockdown on odontoblastic differentiation was reduced after treatment with an IKK inhibitor.</p> <p><b>Conclusions</b>: Our data confirmed that NRAGE is an important regulator of odontogenic differentiation of odontoblasts by inhibiting the NF-κB signaling pathway through binding to IKKβ.</p> <p><b>Abbreviations</b>: Nrage: neurotrophin receptor-interacting MAGE homologue; DSP: dentin sialophospho protein; DMP-1: dentin matrix protein-1; BMP: bone morphogenetic protein; Wnt: wingless; NF-κB: nuclear factor of activated B cells; DAPI: 4′,6-diamidino-2-phenylindole; KO: knockout; DPCs: dental pulp cells; AA: ascorbic acid; β-Gly: β-glycerophosphate; Dex: dexamethasone; co-IP: co-immunoprecipitation; IκB: inhibitor of NF-κB; IKK: IκB kinase</p