Human genome-wide repair map of DNA damage caused by the cigarette smoke carcinogen benzo[a]pyrene

Benzo[a]pyrene (BaP) is a widespread potent carcinogen found in food, coal tar, cigarette smoke, and industrial smoke. Cigarette smoking is the leading cause of lung cancer, and the mutagenesis in smoking-associated lung cancer is determined by multiple factors, including nucleotide excision repair. We have developed a general method for genome-wide mapping of nucleotide excision repair at single-nucleotide resolution and applied it to generate repair maps of UV- and BaP-induced DNA damage in human. Results show a novel sequence specificity of BaP diol epoxide-deoxyguanosine repair. This general method can be used to study repair of all types of DNA damages that undergo nucleotide excision repair

Does Gender Make a Difference in Deception? The Effect of Transcranial Direct Current Stimulation Over Dorsolateral Prefrontal Cortex

Neuroimaging studies have indicated a correlation between dorsolateral prefrontal cortex (DLPFC) activity and deceptive behavior. We applied a transcranial direct current stimulation (tDCS) device to modulate the activity of subjects’ DLPFCs. Causal evidence of the neural mechanism of deception was obtained. We used a between-subject design in a signaling framework of deception, in which only the sender knew the associated payoffs of two options. The sender could freely choose to convey the truth or not, knowing that the receiver would never know the actual payment information. We found that males were more honest than females in the sham stimulation treatment, while such gender difference disappeared in the right anodal/left cathodal stimulation treatment, because modulating the activity of the DLPFC using right anodal/left cathodal tDCS only significantly decreased female subjects’ deception

Modulating the Activity of the DLPFC and OFC Has Distinct Effects on Risk and Ambiguity Decision-Making: A tDCS Study

Human beings are constantly exposed to two types of uncertainty situations, risk and ambiguity. Neuroscientific studies suggest that the dorsolateral prefrontal cortex (DLPFC) and the orbital frontal cortex (OFC) play significant roles in human decision making under uncertainty. We applied the transcranial direct current stimulation (tDCS) device to modulate the activity of participants’ DLPFC and OFC separately, comparing the causal relationships between people’s behaviors and the activity of the corresponding brain cortex when confronted with situations of risk and ambiguity. Our experiment employed a pre–post design and a risk/ambiguity decision-making task, from which we could calculate the preferences via an estimation model. We found evidences that modulating the activity of the DLPFC using right anodal/left cathodal tDCS significantly enhanced the participants’ preferences for risk, whereas modulating the activity of the OFC with right anodal/left cathodal tDCS significantly decreased the participants’ preferences for ambiguity. The reverse effects were also observed in the reversed tDCS treatments on the two areas. Our results suggest that decision-making processes under risk and ambiguity are complicated and may be encoded in two distinct circuits in our brains as the DLPFC primarily impacts decisions under risk whereas the OFC affects ambiguity

Associations of lipids and lipid-lowering drugs with risk of stroke: a Mendelian randomization study

BackgroundStroke is a leading cause of death worldwide, but it is unclear whether circulating lipids and lipid-lowering drugs are causally associated with stroke and its subtypes.MethodsWe used two-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-lowering drugs on stroke and its subtypes.ResultsThe inverse variance weighted Mendelian randomization (IVW-MR) revealed the low-density lipoprotein cholesterol (LDL-C) (OR, 1.46; 95% CI, 1.17–1.83; p = 0.0008) and apolipoprotein B (apoB) (OR, 1.46; 95% CI, 1.21–1.77; p = 0.0001) was positively correlated with large artery stroke (LAS). However, no causal effect was found in LDL-C and apoB on LAS risk when we conducted mvMR. The IVW-MR also found a suggestive evidence that decreased LDL-C levels mediated by the PCSK9 (proprotein convertase subtilisin-kexin type 9) gene were associated with a reduced risk of any stroke (AS) (OR, 1.31; 95% CI, 1.13–1.52; p = 0.0003), any ischemic stroke (AIS) (OR, 1.29; 95% CI, 1.10–1.51; p = 0.001), and LAS (OR, 1.73; 95% CI, 1.15–2.59; p = 0.008), while NPC1L1 (Niemann-Pick C1-like protein)-mediated LDL-C levels were associated with a higher risk of small vessel stroke (SVS) (OR, 6.10; 95% CI, 2.13–17.43; p = 0.0008). The SMR revealed that expression of PCSK9 was associated with risk of AS (OR, 1.15; 95% CI, 1.03–1.28; p = 0.01), AIS (OR, 1.02; 95% CI, 1.14–1.29; p = 0.03), cardioembolic stroke (CES) (OR, 1.28; 95% CI, 1.01–1.61; p = 0.04). And, a significant association was found between the expression of NPC1L1 and the risk of SVS (OR, 1.15; 95% CI, 1.00–1.32; p = 0.04).ConclusionWe cautiously find that LDL-C and apoB was positively correlated with LAS. These findings suggest that the reducing LDL-C levels could be an effective prevention strategy for reducing the risk of stroke

Draft genome sequence of the Tibetan antelope

The Tibetan antelope (Pantholops hodgsonii) is endemic to the extremely inhospitable high-altitude environment of the Qinghai-Tibetan Plateau, a region that has a low partial pressure of oxygen and high ultraviolet radiation. Here we generate a draft genome of this artiodactyl and use it to detect the potential genetic bases of highland adaptation. Compared with other plain-dwelling mammals, the genome of the Tibetan antelope shows signals of adaptive evolution and gene-family expansion in genes associated with energy metabolism and oxygen transmission. Both the highland American pika, and the Tibetan antelope have signals of positive selection for genes involved in DNA repair and the production of ATPase. Genes associated with hypoxia seem to have experienced convergent evolution. Thus, our study suggests that common genetic mechanisms might have been utilized to enable high-altitude adaptation

De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk

Nuclear versus mitochondrial DNA: evidence for hybridization in colobine monkeys

<p>Abstract</p> <p>Background</p> <p>Colobine monkeys constitute a diverse group of primates with major radiations in Africa and Asia. However, phylogenetic relationships among genera are under debate, and recent molecular studies with incomplete taxon-sampling revealed discordant gene trees. To solve the evolutionary history of colobine genera and to determine causes for possible gene tree incongruences, we combined presence/absence analysis of mobile elements with autosomal, X chromosomal, Y chromosomal and mitochondrial sequence data from all recognized colobine genera.</p> <p>Results</p> <p>Gene tree topologies and divergence age estimates derived from different markers were similar, but differed in placing <it>Piliocolobus/Procolobus </it>and langur genera among colobines. Although insufficient data, homoplasy and incomplete lineage sorting might all have contributed to the discordance among gene trees, hybridization is favored as the main cause of the observed discordance. We propose that African colobines are paraphyletic, but might later have experienced female introgression from <it>Piliocolobus</it>/<it>Procolobus </it>into <it>Colobus</it>. In the late Miocene, colobines invaded Eurasia and diversified into several lineages. Among Asian colobines, <it>Semnopithecus </it>diverged first, indicating langur paraphyly. However, unidirectional gene flow from <it>Semnopithecus </it>into <it>Trachypithecus </it>via male introgression followed by nuclear swamping might have occurred until the earliest Pleistocene.</p> <p>Conclusions</p> <p>Overall, our study provides the most comprehensive view on colobine evolution to date and emphasizes that analyses of various molecular markers, such as mobile elements and sequence data from multiple loci, are crucial to better understand evolutionary relationships and to trace hybridization events. Our results also suggest that sex-specific dispersal patterns, promoted by a respective social organization of the species involved, can result in different hybridization scenarios.</p

A comprehensive re-understanding of the OM-hosted nanopores in the marine Wufeng-Longmaxi shale formation in South China by organic petrology, gas adsorption, and X-ray diffraction studies

The overmature marine Ordovician-Silurian Wufeng-Longmaxi (WF-LMX) formation shale is the most important exploration target for shale gas in South China. In this study, WF-LMX shale samples from Well XY-1 in the Northwestern Guizhou Province (NGP) were selected to comprehensively investigate organic matter (OM) assemblages and OM-hosted nanopores. Petrographic observations under an optical microscope and a scanning electron microscope (SEM) revealed that the OM in the WF-LMX shale is predominately solid bitumen (pyrobitumen), followed by organic zooclasts (predominantly as graptolites), with a minor amount of micrinites (as the heavier conversion products of the oil-prone kerogen macerals). Additionally, the degraded alginites were traced by their bright halo feature in reflected light and blurred fluorescence in blue light when enhancing the exposure intensity, which demonstrates that the previously deposited alginites in the WF-LMX shale were basically converted to hydrocarbons. SEM imaging revealed that the secondary OM pores associated with hydrocarbon generation are pervasive in pyrobitumen, while undeveloped in organic zooclasts and micrinites. Conversely, the good linear relationship between TOC contents and methane absorbed amounts indicates that there must be numerous SEM-invisible pores existed in both the solid bitumen and organic zooclasts in addition to the secondary pores. Aiming to certify and quantify the SEM-invisible pores, the OM were separated from the WF-LMX shale and then were subjected to a series physical and chemical measurements. The combined N-2 and CO2 adsorption on the OM isolates of the WF-LMX shale further revealed two pore concentration sections, i.e., pores of 0.33-0.5 nm and 1.2-2.0 nm within the micropore regime, which contributed approximately 82% and 18% to the total surface area and pore volume of the OM, respectively. X-ray diffraction testing further correlated the micropores to the spacing of aromatic rings and macromolecular structural units that constitute the OM. As such, it is the micropores related to the chemical structure of the OM that essentially determine the sorptive capacity of OM and also the WF-LMX bulk shale, whereas the main contribution of SEM-visible OM pores is affording the effective porosity for gas storage. Overall, the clarification of OM assemblages, carriers of secondary OM pores, and existence and origin of OM micropores in the WF-LMX shale provide a further understanding of the generation and occurrence of shale gas in South China

Quantum Nonlocality in Any Forked Tree-Shaped Network

In the last decade, much attention has been focused on examining the nonlocality of various quantum networks, which are fundamental for long-distance quantum communications. In this paper, we consider the nonlocality of any forked tree-shaped network, where each node, respectively, shares arbitrary number of bipartite sources with other nodes in the next “layer”. The Bell-type inequalities for such quantum networks are obtained, which are, respectively, satisfied by all (tn−1)-local correlations and all local correlations, where tn denotes the total number of nodes in the network. The maximal quantum violations of these inequalities and the robustness to noise in these networks are also discussed. Our network can be seen as a generalization of some known quantum networks