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Radicals can be formed expeditiously through the direct irradiation of an electron donor‐acceptor (EDA) complex. Herein, we show a photocatalyst‐free strategy for gem‐difluoroalkenes synthesis realized by photo‐irradiation of the EDA complexes, which can be generated in situ between N‐alkylpyridinium salts and Hantzsch ester without any other additives. A wide variety of readily available alkylamines underwent deaminative defluoroalkylation to provide the corresponding gem‐difluoroalkenes. This reaction system exhibits high reactivity and good functional group tolerance and provides a practical and effective entry to a broad range of α‐alkyl‐substituted gem‐difluoroalkenes. [ABSTRACT FROM AUTHOR]

The liquid biopsy is being integrated into cancer diagnostics and surveillance. However, critical questions still remain, such as how to precisely evaluate cancer mutation burden and interpret the corresponding clinical implications. Herein, we evaluated the role of peripheral blood cell‐free DNA (cfDNA) in characterizing the dynamic mutation alterations of 48 cancer driver genes from cervical cancer patients. We performed targeted deep sequencing on 93 plasma cfDNA from 57 cervical cancer patients and from this developed an algorithm, allele fraction deviation (AFD), to monitor in an unbiased manner the dynamic changes of genomic aberrations. Differing treatments, including chemotherapy (n = 22), radiotherapy (n = 14) and surgery (n = 15), led to a significant decrease in AFD values (Wilcoxon, p = 0.029). The decrease of cfDNA AFD values was accompanied by shrinkage in the size of the tumor in most patients. However, in a subgroup of patients where cfDNA AFD values did not reflect a reduction in tumor size, there was a detection of progressive disease (metastasis). Furthermore, a low AFD value at diagnosis followed a later increase of AFD value also successfully predicted relapse. These results show that plasma cfDNA, together with targeted deep sequencing, may help predict treatment response and disease development in cervical cancer. What's new? Liquid biopsy is increasingly being integrated into cancer diagnostics and surveillance. However, critical questions still remain, such as how to precisely evaluate cancer mutation burden and infer clinical implications. Here, the authors develop a new algorithm that evaluates in an unbiased manner the mutation deviation of every single site in the target regions covered by a cancer panel, including the sites that usually fail to pass the single nucleotide variations (SNV)‐calling criteria of most algorithms. By analyzing 93 cervical cancer samples, they demonstrate that this algorithm is able to efficiently monitor patient response to treatment and prognosticate tumor progression. [ABSTRACT FROM AUTHOR]

Introduction: Targeted therapies are based on specific gene alterations. Various specimen types have been used to determine gene alterations, however, no systemic comparisons have yet been made. Herein, we assessed alterations in selected cancer‐associated genes across varying sample sites in lung cancer patients. Materials and Methods: Targeted deep sequencing for 48 tumor‐related genes was applied to 153 samples from 55 lung cancer patients obtained from six sources: Formalin‐fixed paraffin‐embedded (FFPE) tumor tissues, pleural effusion supernatant (PES) and pleural effusion cell sediments (PEC), white blood cells (WBCs), oral epithelial cells (OECs), and plasma. Results: Mutations were detected in 96% (53/55) of the patients and in 83% (40/48) of the selected genes. Each sample type exhibited a characteristic mutational pattern. As anticipated, TP53 was the most affected sequence (54.5% patients), however this was followed by NOTCH1 (36%, across all sample types). EGFR was altered in patient samples at a frequency of 32.7% and KRAS 10.9%. This high EGFR/ low KRAS frequency is in accordance with other TCGA cohorts of Asian origin but differs from the Caucasian population where KRAS is the more dominant mutation. Additionally, 66% (31/47) of PEC samples had copy number variants (CNVs) in at least one gene. Unlike the concurrent loss and gain in most genes, herein NOTCH1 loss was identified in 21% patients, with no gain observed. Based on the relative prevalence of mutations and CNVs, we divided lung cancer patients into SNV‐dominated, CNV‐dominated, and codominated groups. Conclusions: Our results confirm previous reports that EGFR mutations are more prevalent than KRAS in Chinese lung cancer patients. NOTCH1 gene alterations are more common than previously reported and reveals a role of NOTCH1 modifications in tumor metastasis. Furthermore, genetic material from malignant pleural effusion cell sediments may be a noninvasive manner to identify CNV and participate in treatment decisions. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract During the past decades, improving patient neurological recovery following spinal cord injury (SCI) has remained a challenge. An effective treatment for SCI would not only reduce fractured elements and isolate developing local glial scars to promote axonal regeneration but also ameliorate secondary effects, including inflammation, apoptosis, and necrosis. Three-dimensional (3D) scaffolds provide a platform in which these mechanisms can be addressed in a controlled manner. Polymer scaffolds with favorable biocompatibility and appropriate mechanical properties have been engineered to minimize cicatrization, customize drug release, and ensure an unobstructed space to promote cell growth and differentiation. These properties make polymer scaffolds an important potential therapeutic platform. This review highlights the recent developments in polymer scaffolds for SCI engineering. Statement of Significance How to improve the efficacy of neurological recovery after spinal cord injury (SCI) is always a challenge. Tissue engineering provides a promising strategy for SCI repair, and scaffolds are one of the most important elements in addition to cells and inducing factors. The review highlights recent development and future prospects in polymer scaffolds for SCI therapy. The review will guide future studies by outlining the requirements and characteristics of polymer scaffold technologies employed against SCI. Additionally, the peculiar properties of polymer materials used in the therapeutic process of SCI also have guiding significance to other tissue engineering approaches. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome (mitogenome) of diamond dove (Geopelia cuneata) was first determined in this study. The mitogenome is 17,880 bp in size and composed of 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes, and a control region. The overall nucleotide composition is 30.11% of A, 13.66% of G, 25.11% of T, and 31.13% of C. The mitochondrial structure and gene order were similar to other Columbidae species. Phylogenetic analysis suggested that G. cuneata was placed as sister to G. striata of the same genus. The data could provide valuable information for further studies on conservation genetics and evolution of G. cuneata. [ABSTRACT FROM AUTHOR]

The complete mitogenome of a lorikeet, Trichoglossus rubritorquis (Psittaciformes, Loriidae), was determined first in the genus Trichoglossus. The assembled mitogenome was 17,915 bp and composed of 13 protein-coding genes, 22 tRNAs, two rRNAs and two control regions. Nucleotide composition of T. rubritorquis mitogenome was 30.20% A, 33.30% C, 14.04% G, and 22.46% T, with an A + T bias of 52.66%. ML tree based on 13 protein-coding genes indicated that, Melopsittacus undulatus of the family Psittacidae was the closest related species to T. rubritorquis. This result suggested that lorikeets might still be in the family Psittacidae. [ABSTRACT FROM AUTHOR]

The first complete mitogenome of Hong Kong paradise fish (Macropodus hongkongensis) was determined in this study. The assembled mitogenome is 16,494 bp and consisted of 13 protein-coding genes, 22 tRNAs, 2 rRNAs, and a control region. Nucleotide composition of the complete mitogenome is 30.6% A, 24.8% C, 14.8% G, and 29.8% T, with an A + T bias of 60.4%. The maximum-likelihood tree based on 13 protein-coding genes showed that M. erythropterus was the closest related species to M. hongkongensis. [ABSTRACT FROM AUTHOR]

The complete mitochondrial genome of Lumbricus rubellus was analyzed by next-generation sequencing. The mitogenome was 15,464 bp in length, comprising 13 protein-coding genes (PCGs), 22 transfer RNAs, 2 ribosomal RNAs, and a non-coding region. The phylogenetic analysis of 13 PCGs within the class Oligochaeta suggested that L. rubellus was placed as sister to L. terrestris of the same genus. The results obtained here can contribute to the phylogenetic analysis of earthworms. [ABSTRACT FROM AUTHOR]

Here, the complete mitochondrial genome (mitogenome) of Drawida gisti was sequenced and compared with the mitogenomes of other Metagynophora species. The circular mitogenome was 14,648 bp in length and contained two ribosomal RNA genes (rRNAs), 13 protein-coding genes (PCGs), and 22 transfer RNA genes (tRNAs). The types of constitutive genes and the direction of the coding strand that appeared in Drawida mitogenome were identical to those observed in other Metagynophora species, except for a missing lengthy non-coding region. The conservative relationships between Drawida species were supported by the overall analyses of 13 PCGs, two rRNAs, and 22 tRNAs. A comparison of the Metagynophora mitogenomes revealed that the ATP8 gene possessed the highest polymorphism among the 13 PCGs and two rRNAs. Phylogenetic analysis suggested that the Moniligastridae contained Drawida , which is a primitive Metagynophora group. Our study provides a step forward toward elucidating the evolutionary linkages within Drawida and even Metagynophora. • Extremely small mitogenome size of Drawida gisti • Absence of lengthy non-coding regions in Drawida mitogenomes • Significant difference in codon usage of mitochondrial genes between Drawida and other earthworms • Conservative relationships of Metagynophora supported by mitogenomes [ABSTRACT FROM AUTHOR]

Investigation of spontaneous mutations by next-generation sequencing technology has attracted extensive attention lately due to the fundamental roles of spontaneous mutations in evolution and pathological processes. However, these studies only focused on the mutations accumulated through many generations during long-term (possibly be years of) culturing, but not the freshly generated mutations that occur at very low frequencies. In this study, we established a molecularly barcoded deep sequencing strategy to detect low abundant spontaneous mutations in genomes of bacteria cell cultures. Genome-wide spontaneous mutations in 15 Escherichia coli cell culture samples were defined with a high confidence ( P < 0.01). We also developed a hotspot-calling approach based on the run-length encoding algorithm to find the genomic regions that are vulnerable to the spontaneous mutations. The hotspots for the mutations appeared to be highly conserved across the bacteria samples. Further biological annotation of these regions indicated that most of the spontaneous mutations were located at the repeat domains or nonfunctional domains of the genomes, suggesting the existence of mechanisms that could somehow prevent the occurrence of mutations in crucial genic areas. This study provides a more faithful picture of mutation occurrence and spectra in a single expansion process without long-term culturing., (Copyright © 2018 by the Genetics Society of America.)

Motivation: DNA methylation is an important epigenetic modification that has essential role in gene regulation, cell differentiation and cancer development. Bisulfite sequencing is a widely used technique to obtain genome-wide DNA methylation profiles, and one of the key tasks of analyzing bisulfite sequencing data is to detect differentially methylated regions (DMRs) among samples under different treatment conditions. Although numerous tools have been proposed to detect differentially methylated single CpG site (DMC) between samples, methods for direct DMR detection, especially for complex study designs, are largely limited., Results: We present a new software, GetisDMR, for direct DMR detection. We use beta-binomial regression to model the whole-genome bisulfite sequencing data, where variations in methylation levels and confounding effects have been accounted for. We employ a region-wise test statistic, which is derived from local Getis-Ord statistics and considers the spatial correlation between nearby CpG sites, to detect DMRs. Unlike existing methods, that attempt to infer DMRs from DMCs based on empirical criteria, we provide statistical inference for direct DMR detection. Through extensive simulations and an application to two mouse datasets, we demonstrate that GetisDMR achieves better sensitivities, positive predictive values, more exact locations and better agreement of DMRs with current biological knowledge., Availability and Implementation: It is available at https://github.com/DMU-lilab/GetisDMR CONTACTS: y.wen@auckland.ac.nz or zhiguangli@dlmedu.edu.cnSupplementary information: Supplementary data are available at Bioinformatics online., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)