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Background Previous studies have suggested that β2-adrenergic receptor (ADRB2) is associated with COPD. However, the role of genetic polymorphisms in ADRB2 on COPD has not been evaluated yet. Methods In this study, SNaPshot genotyping, luciferase assay, chromatin immunoprecipitation and real-time polymerase chain reaction were adopted to investigate the association between ADRB2 genetic polymorphisms and COPD, comprehensively. Results One single nucleotide polymorphism (rs12654778), located upstream of ADRB2, showed a significant association with COPD by the logistic regression analysis after adjusting for age, sex and smoking history (p=0.04) in 200 COPD patients and 222 controls from southwest Chinese population. Furthermore, the luciferase assay indicated that rs12654778-A allele reduced the relative promoter activity by ~26% compared with rs12654778-G allele (p=0.0034). The chromatin immunoprecipitation analysis demonstrated that rs12654778 modulated the binding affinity of transcription factor neurofibromin 1. In addition, a significantly reduced expression of ADRB2 in COPD patients was observed, compared with normal controls (p=0.017). Conclusion Our findings suggest a previously unknown mechanism linking allele-specific effects of rs12654778 on ADRB2 expression to COPD onset, for the first time.

The Bama Xiang pig (BMX) is a famous early-maturing Chinese indigenous breed with a two-end black coat. To uncover the genetic basis of the BMX phenotype, we conducted comparative genomic analyses between BMX and East Asian wild boars and Laiwu pigs, respectively. Genes under positive selection were enriched in pathways associated with gonadal hormone and melanin synthesis, consistent with the phenotypic changes observed during development in BMX pigs. We also performed differentially expressed gene analysis based on RNA-seq data from pituitary tissues of BMX and Large White pigs. The CTTNBP2NL, FRS2, KANK4, and KATNAL1 genes were under selection and exhibited expressional changes in the pituitary tissue, which may affect BMX pig puberty. Our study demonstrated the positive selection of early maturity in the development of BMX pigs and advances our knowledge on the role of regulatory elements in puberty evolution in pigs.

Taiwanofungus camphoratus has been reported to have antitumor effects against various cancer cells. The aim of this study was to investigate the direct inhibitory effect of By-1 (3-isobutyl-l-methoxy-4-[4'-(3-methylbut-2-enyloxy)phenyl]-1H-pyrrole-2,5-dione), a compound from spent broth from submerged cultures of T. camphoratus, on human lung adenocarcinoma cells and to determine the molecular mechanism underlying this effect. The growth-inhibitory assay and colony formation assay showed that cell viability was significantly decreased. A By-1 concentration of 300 μmol/L caused 73.55% cell death and at a concentration of 240 μmol/L led to a 58% reduction in the number of colonies. The wound-healing assay showed that the distance of migration was 0.3 times shorter than that of untreated cells. Flow cytometry revealed that By-1 could suppress DNA synthesis, cause cell cycle arrest at the S phase, and induce apoptosis in a reactive oxygen species-dependent manner. Furthermore, the expression of caspase-3 and P53 was 4 times higher than that in untreated cells, and the antiapoptotic protein Bcl-2 was decreased 2 times compared with the protein in untreated cells. It is interesting to note that apoptosis and autophagy were both induced during treatment with By-1, and autophagy inhibition decreased cell proliferation. By-1 potently inhibited the growth of SPCA-1 cells by inducing cell cycle arrest and apoptosis. The combination of proapoptosis agents and antiautophagy agents could effectively enhance anticancer efficacy, which may be a new strategy in treating non-small cell lung cancer.

Objective To observe the comparison of the clinical efficacy between penetration needling from Neiguān ( PC 6) to Waiguān ( TE 5) and western medicine estazolam for insomnia. Methods Sixty insomnia patients were divided into 2 groups according to the random number table, 30 cases in each group. Penetration needling from PC 6 to TE 5 was mainly adopted in acupuncture group for once a day, 5 times a week, and treatment for 4 weeks was 1 course of treatment. Estazolam was orally given in medicine group before sleep every night in a dosage of 1 mg per time, and treatment for 4 weeks was 1 course of treatment. After 4 weeks, the clinical efficacy and the Pittsburgh Sleep Quality Index (PSQI) score were compared respectively between the two groups. Results The total effective rate was 90.00% in acupuncture group and 63.33% in medicine group, and the difference was statistically significant (P Conclusion The penetration needling of complementary acupoints from PC 6 to TE 5 was simple and convenient which can significantly improve the patients' sleep quality.

The Pamirs, among the world's highest mountains in Central Asia, are one of homelands with the most extreme high altitude for several ethnic groups. The settlement history of modern humans on the Pamirs remains still opaque. Herein, we have sequenced the mitochondrial DNA (mtDNA) genomes of 382 individuals belonging to eight populations from the Pamirs and the surrounding lowlands in Central Asia. We construct the Central Asian (including both highlanders and lowlanders) mtDNA haplogroup tree at the highest resolution. All the matrilineal components are assigned into the defined mtDNA haplogroups in East and West Eurasians. No basal lineages that directly emanate from the Eurasian founder macrohaplogroups M, N, and R are found. Our data support the origin of Central Asian being the result of East-West Eurasian admixture. The coalescence ages for more than 93% mtDNA lineages in Central Asians are dated after the last glacial maximum (LGM). The post-LGM and/or later dispersals/admixtures play dominant roles in shaping the maternal gene pool of Central Asians. More importantly, our analyses reveal the mtDNA heterogeneity in the Pamir highlanders, not only between the Turkic Kyrgyz and the Indo-European Tajik groups, but also among three highland Tajiks. No evidence supports positive selection or relaxation of selective constraints in the mtDNAs of highlanders as compared to that of lowlanders. Our results suggest a complex history for the peopling of Pamirs by multiple waves of migrations from various genetic resources during different time scales.

Biofilm formation, loose deposit accumulation and water quality deterioration in drinking water distribution systems have been widely reported. However, the accumulation and distribution of harbored elements and microbes in the different niches (loose deposits, PVC-U biofilm, and HDPE biofilm) and their corresponding potential contribution to water quality deterioration remain unknown. This precludes an in-depth understanding of water quality deterioration and the development of proactive management strategies. The present study quantitatively evaluated the distribution of elements, ATP, Aeromonas spp., and bacterial communities in distribution pipes (PVC-U, D = 110 mm, loose deposit and biofilm niches) and household connection pipes (HDPE, D = 32 mm, HDPE biofilm niches) at ten locations in an unchlorinated distribution system. The results show that loose deposits in PVC-U pipes, acting as sinks, constitute a hotspot (highest total amount per meter pipe) for elements, ATP, and target bacteria groups (e.g., Aeromonas spp., Mycobacterium spp., and Legionella spp.). When drinking water distribution system niches with harbored elements and microbes become sources in the event of disturbances, the highest quality deterioration potential (QDP) is that of HDPE biofilm; this can be attributed to its high surface-to-volume ratio. 16s rRNA analysis demonstrates that, at the genus level, the bacterial communities in the water, loose deposits, PVC-U biofilm, and HDPE biofilm were dominated, respectively, by Polaromonas spp. (2–23%), Nitrosipra spp. (1–47%), Flavobacterium spp. (1–36%), and Flavobacterium spp. (5–67%). The combined results of elemental composition and bacterial community analyses indicate that different dominant bio-chemical processes might occur within the different niches—for example, iron-arsenic oxidizing in loose deposits, bio-calumniation in PVC-U biofilm, and methane oxidizing in HDPE biofilm. The release of 20% loose deposits, 20% PVC-U biofilm and 10% HDPE biofilm will cause significant changes of water bacterial community.

A toroidal soft x-ray array system for spectrum and intensity measurements on the EXL-50 spherical tokamak is described. Silicon drift detectors and digital multichannel analyzers are adopted for all 21 channels of the array, and an average energy resolution of 147 eV at 5.89 keV has been achieved at count rates over 500 kcps. In total, 20 channels of the array are symmetrically observed in both co- and counter-current directions on the EXL-50 mid-plane with a spatial resolution of around 10 cm, and the remaining one serves as a background reference channel. Tungsten emissions from tungsten coating of the limiters on the central post are observed. The influence of hard x rays on measured soft x-ray spectra and system operation is discussed.

As a result of vitamin A abuse, excessive retinoic acid can induce apoptosis in neural cells. Mild-hypothermia and cold-inducible protein RBM3 protect neural cells from apoptosis. However, whether hypothermia/RBM3 protect neural cells from retinoic acid-induced apoptosis remains unclear. The SH-SY5Y neuroblastoma cell line, a common neural cell model of apoptosis, was employed here. Interestingly, retinoic acid overdose induced apoptosis in SH-SY5Y cells, which was prevented by mild-hypothermia. When RBM3 was silenced, hypothermia-related protection was completely abolished. RBM3 overexpression significantly prevented retinoic acid-induced apoptosis. Screening of signaling pathways revealed that RBM3 overexpression markedly inhibited retinoic acid-induced upregulation of p38 and JNK signaling, and antagonized downregulation of AMPK signaling. Subsequent assays demonstrated that p38 and JNK signaling were pro-apoptotic, while AMPK was anti-apoptotic. Overall, these data showed that mild-hypothermia protects neural cells from retinoic acid-induced apoptosis via induction of RBM3, which subsequently mediates the neuroprotective effects via AMPK, p38 and JNK signaling.

Preaxial polydactyly (PPD) is congenital hand malformation characterized by the duplication of digit. Herein, we scan the genome-wide SNPs for a large Chinese family with PPD-II/III. We employ the refined IBD algorithm to identify the identity-by-decent (IBD) segments and compare the frequency among the patients and normal relatives. A total of 72 markers of 0.01 percentile of the permutation are identified as the peak signals. Among of them, 57markers locate on chromosome 7q36 which is associated with PPD. Further analyses refine the mapping of candidate region in chromosome 7q36 into two 380 Kb fragments within LMBR1 and SHH respectively. IBD approach is a suitable method for mapping causal gene of human disease. Target-enrichment sequencing as well as functional experiments are required to illustrate the pathogenic mechanisms for PPD in the future. Electronic supplementary material The online version of this article (doi:10.1186/s41065-017-0040-6) contains supplementary material, which is available to authorized users.

RNA editing was first discovered in mitochondrial RNA molecular. However, whether adenosine-to-inosine (A-to-I) RNA editing has functions in nuclear genes involved in mitochondria remains elusive. Here, we retrieved 707,246 A-to-I RNA editing sites in Macaca mulatta leveraging massive transcriptomes of 30 different tissues and genomes of nine tissues, together with the reported data, and found that A-to-I RNA editing occurred frequently in nuclear genes that have functions in mitochondria. The mitochondrial structure, the level of ATP production, and the expression of some key genes involved in mitochondrial function were dysregulated after knocking down the expression of ADAR1 and ADAR2, the key genes encoding the enzyme responsible for RNA editing. When investigating dynamic changes of RNA editing during brain development, an amino-acid-changing RNA editing site (I234/V) in MFN1, a mediator of mitochondrial fusion, was identified to be significantly correlated with age, and could influence the function of MFN1. When studying transcriptomes of brain disorder, we found that dysregulated RNA editing sites in autism were also enriched within genes having mitochondrial functions. These data indicated that RNA editing had a significant function in mitochondria via their influence on nuclear genes.

// Hui Zhao 1, 2, * , Siqi Wang 1, 3, * , Lixia Guo 1, 3, * , Yanli Du 1, 3 , Linlin Liu 1, 3 , Tengfei Ma 1, 3 , Newton O. Otecko 4, 5 , Canpeng Li 6 and Yaping Zhang 1, 4 1 State Key Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming 650091, P.R. China 2 Key Laboratory for Animal Genetic Diversity and Evolution of High Education in Yunnan Province, Yunnan University, Kunming 650091, P.R. China 3 School of Life Science, Yunnan University, Kunming 650091, P.R. China 4 State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, P.R. China 5 Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, P.R. China 6 School of Chemical Science and Technology, Yunnan University, Kunming 650091, P.R. China * These authors contributed equally to this work Correspondence to: Canpeng Li, email: lcppp1974@sina.com Yaping Zhang, email: zhangyp@mail.kiz.ac.cn Keywords: microRNA, difference, BSE, PRNP , 3’UTR Received: December 02, 2016 Accepted: March 30, 2017 Published: May 02, 2017 ABSTRACT Bovine spongiform encephalopathy, a member of transmissible spongiform encephalopathies, has not been reported in buffaloes, Bubalus bubalis . Prion protein (PrP), encoded by the prion protein gene ( PRNP ), is fundamental in the pathogenesis of transmissible spongiform encephalopathies. We previously showed that cattle express more PrP proteins but lower PRNP mRNA than buffaloes in several pivotal tissues like the obex. Therefore, we sought to establish whether genetic variability in PRNP 3’UTR, mediated by miRNA down-regulation, causes PrP expression differences between cattle and buffaloes. We annotated the 3’UTR of buffalo PRNP gene by 3’RACE experiment. A total of 92 fixed differences in the complete 3’UTR (~ 3 kb) were identified between 13 cattle and 13 buffaloes. Resequencing of UTR-C (g.786-1436) and UTR-B (g.778-1456) fragments confirmed that all mutations except g.1022T in cattle are fixed differences between 147 cattle and 146 buffaloes. In addition, analysis of the variation of ΔG between cattle and buffalo sequences reveals four remarkable differences. Two buffalo-specific insertion sites (a 28-bp insertion and an AG insertion in buffalo 3’UTR of PRNP g.970-997 and g. 1088-1089, respectively) and two mutants (g. 1007-1008 TG→CC) create compatible binding sites for miRNAs in buffalo 3’UTR. This was validated through luciferase reporter assays which demonstrated that miR-125b-5p, miR-132-3p, miR-145-5p, miR-331-3p, and miR-338-3p directly act on the fixed difference sites in buffalo 3’UTR. Additional expressional analyses show that these five miRNAs are coexpressed with PRNP in bovine obex tissues. Our study reveals a miRNAs regulated mechanism explaining the differences in prion expression between cattle and buffalo.

The origin, peopling and evolution of human beings have all contributed greatly to shaping the genetic diversity of present human populations, and are the research focus of multiple disciplines. Molecular genetics has tried to deduce the human history through genetic analysis of modern human populations. It proposed the well-recognized out of Africa human origin model with Homo sapiens replaced all the other human species. As modern humans migrated out of Africa, they encountered multiple environmental conditions which could exert selection pressure upon them, as exemplified by the evolutionary elucidation of human phenotypes like skin pigmentation and height as well as physiological traits like lactase tolerance, starch digestion, immune response and hypoxia adaptation. However, this indirect approach could be largely influenced by undetected population structure and model parameter settings, still cannot fully reveal the genuine human history, and sometimes could even produce misleading results based on Occam’s razor theory. Recently, whole genome resequencing is used to directly analyse ancient DNA samples collected from different time periods to investigate a specific history event. In addition, the genetic data from both ancient and modern human populations are systematically compared to obtain a more straightforward elucidation of human history. To be more specific, analyses from archaic human populations have demonstrated strong evidence of gene flow between Homo sapiens and other extinct human species, e.g. Neanderthals and the Danisova hominin, which gave rise to a leaky replacement model. That is, other ancient human species also have contributed to modern human populations. Together with the remaining Homo sapien s genome, the introgression from ancient human species went through genetic drift and natural selection. For example, the EPAS1 gene encoding endothelial Per-Arnt-Sim (PAS) domain protein 1 has been indicated to play an important role in hypoxia adaptation among Tibetan individuals. 31 SNPs of this gene are significantly associated with haemoglobin (Hb) levels, and the Tibetan dominant alleles are significantly associated with low Hb levels, a trait featured in Tibetan hypoxia adaptation. Interestingly, the dominant Tibetan haplotype can only be observed in Tibetans and Danisova hominin with high frequency, and further genetic analysis revealed this gene was from Danisova hominin. Similar stories could also be observed for other human phenotypes and physiological traits. Therefore, as demonstrated by the illustrious example of EPAS1 gene, ancient DNA research is revealing a human history far more complex than what we have inferred from parsimonious models based on modern DNA. In this review, we will briefly overview some key events in human environmental adaptation in the light of ancient DNA findings, and discuss new evidence how natural selection has shaped human populations, which might provide clues for future studies.

Alternative cleavage and polyadenylation (APA) is involved in several important biological processes in animals, e.g. cell growth and development, and cancer progression. The increasing data show that cancer cells are inclined to produce mRNA isoforms with a shortened 3'UTR undergoing APA. For example, the Dicer1 isoform with a shorter 3'untranslated region (3'UTR) was found to be overexpressed in some cancer cells, which may be used as a potential novel prognostic biomarker for cancer. In the present work, a novel electrochemical biosensor for ultrasensitive determination of Dicer1 was designed by using gold nanoparticles and p-sulfonated calix[6]arene functionalized reduced graphene oxide (Au@SCX6-rGO) as nanocarriers. The results showed that the expressions of the shorter 3'UTR (Dicer1-S) both in BT474 and SKBR3 were obviously higher than those of the longer Dicer1 (Dicer1-L) by the constructed biosensor, which agreed well with the result analyzed by the RT-qPCR method. The detection ranges of Dicer1-S and Dicer1-L were 10-14-10-9 M and 10-15-10-10 M. The LODs were 3.5 and 0.53 fM. The specificity of the proposed biosensor was also very high. For the first time, the expressional analysis of different 3'UTRs caused by APA was studied by an electrochemical method. Moreover, the use of a macrocyclic host for constructing an electrochemical/biosensing platform has rarely been reported. The proposed electrochemical sensing strategy is thus expected to provide a new method for determination of novel biomarkers and a novel method for fast and cheap analysis of APA.

By-1 was obtained from spent broth from submerged cultures of Taiwanofungus camphoratus. This report evaluates the effects of By-1 on plate clone formation, wound healing, cell cycle, activated caspase-3 expression, and ROS release in A549 lung cancer cells. The result of plate clone formation assay revealed that By-1 could dramatically inhibit the viability of A549 cells in vitro. The inhibitory effect of By-1 on cell migration was tested using a wound healing assay. Proliferation rates of A549 cells were significantly inhibited following exposure to By-1 (12.5, 50, and 80 μg/mL). Flow cytometry revealed that the extracts increased, in a concentration-dependent manner, the number of cells in the G0/G1 phases of the cell cycle. The results of the caspase-3 experiment suggested that By-1 could induce A549 cells apoptosis, and this apoptosis was related to the release of reactive oxygen species by the A549 cells. All these results indicate that By-1 has potential in anti-lung cancer drug development.

Accelerated losses of biodiversity are a hallmark of the current era. Large declines of population size have been widely observed and currently 22,176 species are threatened by extinction. The time at which a threatened species began rapid population decline (RPD) and the rate of RPD provide important clues about the driving forces of population decline and anticipated extinction time. However, these parameters remain unknown for the vast majority of threatened species. Here we analyzed the genetic diversity data of nuclear and mitochondrial loci of 2,764 vertebrate species and found that the mean genetic diversity is lower in threatened species than in related nonthreatened species. Our coalescence-based modeling suggests that in many threatened species the RPD began ∼123 y ago (a 95% confidence interval of 20-260 y). This estimated date coincides with widespread industrialization and a profound change in global living ecosystems over the past two centuries. On average the population size declined by ∼25% every 10 y in a threatened species, and the population size was reduced to ∼5% of its ancestral size. Moreover, the ancestral size of threatened species was, on average, ∼22% smaller than that of nonthreatened species. Because the time period of RPD is short, the cumulative effect of RPD on genetic diversity is still not strong, so that the smaller ancestral size of threatened species may be the major cause of their reduced genetic diversity; RPD explains 24.1-37.5% of the difference in genetic diversity between threatened and nonthreatened species.

The grey wolf (Canis lupus) is one of the most widely distributed terrestrial mammals, and its distribution and ecology in Europe and North America are largely well described. However, the distribution of grey wolves in southern China is still highly controversial. Several well-known western literatures stated that there were no grey wolves in southern China, while the presence of grey wolves across China has been indicated in A Guide to the Mammals of China, published by Princeton University Press. It is essential to solve this discrepancy since dogs may have originated from grey wolves in southern China. Therefore, we systematically investigated Chinese literatures about wild animal surveys and identified more than 100 articles and books that included information of the distribution of grey wolves in China. We also surveyed the collections of three Chinese natural museums and found 26 grey wolf skins specimens collected across China. Moreover, we investigated the fossil records in China and identified 25 archaeological sites with wolf remains including south China. In conclusion, with the comprehensive summary of Chinese literatures, museum specimens and fossil records, we demonstrate that grey wolves do distribute across all parts of the Chinese mainland, including the most southern parts.

Quality deficiencies in single nucleotide polymorphism (SNP) analyses have important implications. We used missingness rates to investigate the quality of a recently published dataset containing 424 mitochondrial, 211 Y chromosomal, and 160 432 autosomal SNPs generated by a semicustom Illumina SNP array from 5 392 dogs and 14 grey wolves. Overall, the individual missingness rate for mitochondrial SNPs was ~43.8%, with 980 (18.1%) individuals completely missing mitochondrial SNP genotyping (missingness rate=1). In males, the genotype missingness rate was ~28.8% for Y chromosomal SNPs, with 374 males recording rates above 0.96. These 374 males also exhibited completely failed mitochondrial SNPs genotyping, indicative of a batch effect. Individual missingness rates for autosomal markers were greater than zero, but less than 0.5. Neither mitochondrial nor Y chromosomal SNPs achieved complete genotyping (locus missingness rate=0), whereas 5.9% of autosomal SNPs had a locus missingness rate=1. The high missingness rates and possible batch effect show that caution and rigorous measures are vital when genotyping and analyzing SNP array data for domestic animals. Further improvements of these arrays will be helpful to future studies.

Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we utilized 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularlyEPAS1gene in these Tibetan domestic mammals. We also reported a potential function in response to hypoxia for the geneC10orf67, which underwent positive selection in three of the domestic mammals. Our data provides insight into adaptive evolution of high-altitude domestic mammals, and should facilitate the search for additional novel genes involved in the hypoxia response pathway.

Canine transmissible venereal tumor genome reveals ancient introgression from coyotes to pre-contact dogs in North America

Herein, we describe the new agamid species Acanthosaura phongdienensis sp. nov. from central Vietnam based on morphological and genetic data. Males of the new medium-sized species have a snout-vent length of up to 77.4 mm and females up to 64.7 mm. In both genders, the tail is longer than the snout-vent length. A spine occurs on each side of the neck, the rostral scute is entire, and the nuchal and dorsal crests are continuous. A postorbital spine is about half as long as the diameter of the eye-ball, and small lateral scales intermix with large, keeled scales whose tips point backwards and upwards. The new species differs genetically from the closely related species A. brachypoda, A. coronata, and A. lepidogaster by uncorrected p-distances of 13.6%, 21.7%, and 12.8%, respectively. This is the 13th species of Acanthosaura and the eighth species in the genus from Vietnam.

16-core photonic crystal fiber (PCF) was designed. In order to obtain spatially flat in-phase modes, the super-mode near- field properties were studied through method of numerical simulation calculation and according to coupled mode theory. On the based of the scalar Fraunhofer Diffraction, a far- field in-phase super-mode theoretical modeling was presented. According to the modeling, one discussed the influence of the random phase perturbation, the random amplitude perturbation and the polarization direction perturbation on the far-filed intensity distribution, in detail. The results show that both phase perturbation and amplitude perturbation sharply impact the far-filed distribution of interference intensity and contrast. However, the influence of the polarization direction perturbation is not obvious. When the parameterδ, μ and u increases, the field center intensity decreases and the power of the central spot also does, which means the profile of the spot will blur and the beam quality drop.

International audience; Caenophidian snakes include the file snake genus Acrochordus and advanced colubroidean snakes that radiated mainly during the Neogene. Although caenophidian snakes are a well-supported clade, their inferred affinities, based either on molecular or morphological data, remain poorly known or controversial. Here, we provide an expanded molecular phylogenetic analysis of Caenophidia and use three non-parametric measures of support–Shimodaira-Hasegawa-Like test (SHL), Felsentein (FBP) and transfer (TBE) bootstrap measures–to evaluate the robustness of each clade in the molecular tree. That very different alternative support values are common suggests that results based on only one support value should be viewed with caution. Using a scheme to combine support values, we find 20.9% of the 1265 clades comprising the inferred caenophidian tree are unambiguously supported by both SHL and FBP values, while almost 37% are unsupported or ambiguously supported, revealing the substantial extent of phylogenetic problems within Caenophidia. Combined FBP/TBE support values show similar results, while SHL/TBE result in slightly higher combined values. We consider key morphological attributes of colubroidean cranial, vertebral and hemipenial anatomy and provide additional morphological evidence supporting the clades Colubroides, Colubriformes, and Endoglyptodonta. We review and revise the relevant caenophidian fossil record and provide a time-calibrated tree derived from our molecular data to discuss the main cladogenetic events that resulted in present-day patterns of caenophidian diversification. Our results suggest that all extant families of Colubroidea and Elapoidea composing the present-day endoglyptodont fauna originated rapidly within the early Oligocene–between approximately 33 and 28 Mya–following the major terrestrial faunal turnover known as the “Grande Coupure” and associated with the overall climate shift at the Eocene-Oligocene boundary. Our results further suggest that the caenophidian radiation originated within the Caenozoic, with the divergence between Colubroides and Acrochordidae occurring in the early Eocene, at ~ 56 Mya.

Piao chicken, a rare Chinese native poultry breed, lacks primary tail structures, such as pygostyle, caudal vertebra, uropygial gland, and tail feathers. So far, the molecular mechanisms underlying tail absence in this breed remain unclear. We comprehensively employed comparative transcriptomic and genomic analyses to unravel potential genetic underpinnings of rumplessness in the Piao chicken. Our results reveal many biological factors involved in tail development and several genomic regions under strong positive selection in this breed. These regions contain candidate genes associated with rumplessness, including Irx4, Il18, Hspb2, and Cryab. Retrieval of quantitative trait loci (QTL) and gene functions implied that rumplessness might be consciously or unconsciously selected along with the high-yield traits in Piao chicken. We hypothesize that strong selection pressures on regulatory elements might lead to changes in gene activity in mesenchymal stem cells of the tail bud. The ectopic activity could eventually result in tail truncation by impeding differentiation and proliferation of the stem cells. Our study provides fundamental insights into early initiation and genetic basis of the rumpless phenotype in Piao chicken.

The ability to digest dietary lactose is associated with lactase persistence (LP) in the intestinal lumen in human. The genetic basis of LP has been investigated in many populations in the world. Iran has a long history of pastoralism and the daily consumption of dairy products; thus, we aim to assess how LP has evolved in the Iranian population. We recruited 400 adult individuals from seven Iranian ethnic groups, from whom we investigated their lactose tolerance and screened the genetic variants in their lactase gene locus.The LP frequency distribution ranged from 0 to 29.9% in the seven Iranian ethnic groups with an average value of 9.8%. The variants, - 13910*T and - 22018*A, were significantly associated with LP phenotype in Iranians. We found no evidence of hard selective sweep for - 13910*T and - 22018*A in Persians, the largest ethnic group of Iran. The extremely low frequency of - 13915*G in the Iranian population challenged the view that LP distribution in Iran resulted from the demic diffusion, especially mediated by the spread of Islam, from the Arabian Peninsula.Our results indicate the distribution of LP in seven ethnic groups across the Iranian plateau. Soft selective sweep rather than hard selective sweep played a substantial role in the evolution of LP in Iranian populations.

Summary Although gray wolves (Canis lupus) are one of the most widely distributed terrestrial mammals, their origins in China are not well understood. We sequenced six specimens from wolf skins, showing that gray wolves from Southern China (SC) derive from a single lineage, distinct from gray wolves from the Tibetan Plateau and Northern China, suggesting that SC gray wolves may form a distinct subpopulation. Of SC gray wolves, one wolf from Zhejiang carries a genetic component from a canid and had gene flow from a population related to or further diverged from wolves than the dhole. This may indicate that interspecific gene flow likely played an important role in shaping the speciation patterns and population structure in the genus Canis. Our study is the first to survey museum gray wolves' genomes from Southern China, highlighting how sequencing the paleogenome from museum specimens can help us to study extinct species., Graphical Abstract, Highlights • Gray wolves from South China derive from a single lineage • A Zhejiang wolf shows admixture (∼12%–14%) from a deeply diverged canid species • Lowland gray wolf shows close genetic relationship to Tibetan Plateau gray wolves, Biological Sciences; Genomics; Evolutionary Biology

Plasma cholinesterase (PCHE) activity is an important auxiliary test in human clinical medicine. It can distinguish liver diseases from non-liver diseases and help detect organophosphorus poisoning. Animal experiments have confirmed that PCHE activity is associated with obesity and hypertension and changes with physiological changes in an animal's body. The objective of this study was to locate the genetic loci responsible for PCHE activity variation in ducks. PCHE activity of Pekin duck × mallard F2 ducks at 3 and 8 weeks of age were analyzed, and genome-wide association studies were conducted. A region of about 1.5 Mb (21.8-23.3 Mb) on duck chromosome 9 was found to be associated with PCHE activity at both 3 and 8 weeks of age. The top SNP, g.22643979C>T in the butyrylcholinesterase (BCHE) gene, was most highly associated with PCHE activity at 3 weeks (-logP = 21.45) and 8 weeks (-logP = 27.60) of age. For the top SNP, the strong associations of CC and CT genotypes with low PCHE activity and the TT genotype with high PCHE activity indicates the dominant inheritance of low PCHE activity. Problems with block inheritance or linkage exist in this region. This study supports that BCHE is a functional gene for determining PCHE levels in ducks and that the genetic variations around this gene can cause phenotypic variations of PCHE activity.

SUMMARYDespite being one of the most widely distributed terrestrial mammals, the history of gray wolves (Canis lupus) in China is not well understood as their habitats have been destroyed with growing economic development. Using six specimens from wolf skins in Chinese Natural History museums, we sequenced their genome using a modified ancient DNA procedure. Using whole genome sequence analysis, we showed that gray wolves from Southern China (SC) derive from a single lineage, distinct from gray wolves from the Tibetan Plateau (Canis lupus chanco) and Northern China, suggesting that SC gray wolves may form a distinct sub-population. Of SC gray wolves, one wolf from Zhejiang carries a genetic component from a canid that must have diverged earlier from other wolves than jackals did, perhaps through gene flow from a population related to or further diverged from wolves than the dhole, a species distributed in Southern China and Southeast Asia. This may indicate that interspecific gene flow likely played an important role in shaping the speciation patterns and population structure in the genus Canis. Our study is the first to survey museum genomes of gray wolves from Southern China, revealing the presence of an endemic population with ancient interspecific gene flow from a population related to the dhole, and highlighting how sequencing the paleogenome from museum specimens can help us to study extinct species.

Genetic introgression provides material for adaptive evolution, but also confounds our understanding of evolutionary history. This is particularly true for canids, a species complex including dogs, wolves, coyotes, jackals, and other wolf-like carnivores, in which genomic analyses have revealed a complex history of admixture and introgression. Among the most enigmatic canid lineages whose origin and evolutionary relationships remain unresolved are the high-altitude wolves of the Tibetan Plateau, the Tibetan grey wolf and the Himalayan wolf. Here, we use newly assembled genomes of high-altitude Tibetan and Himalayan wolves to explore the evolutionary history and adaptation of this charismatic group. We find that Tibetan and Himalayan wolves are closely related to each other, and that as much as 38-43% of their nuclear genome is derived from an as-yet unrecognized wolf-like lineage that is deeply diverged from living Holarctic wolves and dogs. The EPAS1 haplotype, which is present at high frequencies in Tibetan dog breeds and wolves and confers an adaptive advantage to animals living at high altitudes, was probably derived from this ancient lineage. Our study underscores the complexity of canid evolution and demonstrates how admixture and introgression shape the evolutionary trajectories and adaptation of species.

The Global Deal for Nature sets an ambitious agenda to protect our biosphere through ecosystem conservation and land restoration., The Global Deal for Nature (GDN) is a time-bound, science-driven plan to save the diversity and abundance of life on Earth. Pairing the GDN and the Paris Climate Agreement would avoid catastrophic climate change, conserve species, and secure essential ecosystem services. New findings give urgency to this union: Less than half of the terrestrial realm is intact, yet conserving all native ecosystems—coupled with energy transition measures—will be required to remain below a 1.5°C rise in average global temperature. The GDN targets 30% of Earth to be formally protected and an additional 20% designated as climate stabilization areas, by 2030, to stay below 1.5°C. We highlight the 67% of terrestrial ecoregions that can meet 30% protection, thereby reducing extinction threats and carbon emissions from natural reservoirs. Freshwater and marine targets included here extend the GDN to all realms and provide a pathway to ensuring a more livable biosphere.

The origin and population history of the endangered golden snub-nosed monkey (Rhinopithecus roxellana) remain largely unavailable and/or controversial. We here integrate analyses of multiple genomic markers, including mitochondrial (mt) genomes, Y-chromosomes, and autosomes of 54 golden monkey individuals from all three geographic populations (SG, QL, and SNJ). Our results reveal contrasting population structures. Mt analyses suggest a division of golden monkeys into five lineages: one in SNJ, two in SG, and two in QL. One of the SG lineages (a mixed SG/QL lineage) is basal to all other lineages. In contrast, autosomal analyses place SNJ as the most basal lineage and identify one QL and three SG lineages. Notably, Y-chromosome analyses bear features similar to mt analyses in placing the SG/QL-mixed lineage as the first diverging lineage and dividing SG into two lineages, while resembling autosomal analyses in identifying one QL lineage. We further find bidirectional gene flow among all three populations at autosomal loci, while asymmetric gene flow is suggested at mt genomes and Y-chromosomes. We propose that different population structures and gene flow scenarios are the result of sex-linked differences in the dispersal pattern of R. roxellana. Moreover, our demographic simulation analyses support an origin hypothesis suggesting that the ancestral R. roxellana population was once widespread and then divided into SNJ and non-SNJ (SG and QL) populations. This differs from previous mt-based "mono-origin (SG is the source population)" and "multiorigin (SG is a fusion of QL and SNJ)" hypotheses. We provide a detailed and refined scenario for the origin and population history of this endangered primate species, which has a broader significance for Chinese biogeography. In addition, this study highlights the importance to investigate multiple genomic markers with different modes of inheritance to trace the complete evolutionary history of a species, especially for those exhibiting differential or mixed patterns of sex dispersal.

Dingoes(Canis dingo)are wild canids living in Australia. They have lived isolated from both the wild and the domestic ancestor and are a unique model for studying feralization, the process in which a domestic species escapes human control, adapts to the wild, and diverges from the domestic ancestor into a genetically distinct population. Here, we sequenced the genomes of 10 dingoes and 2 New Guinea Singing Dogs, to study the origins and feralization process of the dingo. Phylogenetic and demographic analyses show that dingoes originate from domestic dogs in southern East Asia, which migrated via Island Southeast Asia to reach Australia 4300-5000 years ago, and subsequently diverged into a genetically distinct population. Selection analysis identified 99 positively selected genes enriched in starch and fat metabolism pathways, indicating a diet change during feralization of dingoes. Interestingly, we found that 14 genes have shifted allele frequencies compared to dogs but not compared to wolves. This suggests that the selection affecting these genes during domestication of the wolf was reversed in the feralization process. One of these genes,ARHGEF7,may promote the formation of neural spine and synapses in hippocampal neurons. Functional assays showed that an A to G mutation inARHGEF7,located in a transcription factor-binding site, decreases the endogenous expression. This suggests thatARHGEF7may have been under selection for behavioral adaptations related to the transitions in environment both from wild to domestic and from domestic back to wild. Our results indicate that adaptation to domestication and feralization primarily affected different genomic regions, but that some genes, related to neurodevelopment, metabolism and reproduction, may have been reversibly affected in the two processes.

A heat pipe coal pile experiment platform was established to test the performance of the heat pipe in the heat transfer of the coal pile. Experiments were carried out to measure and analyze the continuous cooling characteristics and cooling rate of the internal heat dissipation of coal piles of different heights under different temperature heat sources. The results show that when the heat source temperature is higher, there is a greater cooling rate inside the coal pile. The closer it is to the heat source, the more obvious the heat dissipation inside the coal pile will be affected by the heat pipe and heat source. This experiment verifies the feasibility of the heat pipe to automatically and continuously transfers the internal heat of the coal pile under the action of the difference between the outside temperature and the internal temperature of the coal pile, to achieve the purpose of preventing spontaneous combustion of the coal pile.

In order to solve the icing phenomenon of mine wind gap, a physical model of L-type gravity heat pipe was designed in combination with calculation of shaft operating condition, which based on the new idea that geothermal energy of thermostatic formation is used as driving heat source of heat pipe for shaft antifreeze. The numerical simulation showed that the condensation end temperature of the heat pipe could reach 275K. The heat pipe optimization simulation was carried out for the length of the condensation and insulation section of the heat pipe. When the condensing section is 5 m, the effect is the best. The results showed that the temperature at the condenser end of the heat pipe was increased by 275.6K after optimization. The optimized scheme for extracting heat energy from thermostat by heat pipe has a good effect.

Body size is the most important economic trait for animal production and breeding. Several hundreds of loci have been reported to be associated with growth trait and body weight in chickens. The loci are mapped to large genomic regions due to the low density and limited number of genetic markers in previous studies. Herein, we employed comparative population genomics to identify genetic basis underlying the small body size of Yuanbao chicken (a famous ornamental chicken) based on 89 whole genomes. The most significant signal was mapped to the BMP10 gene, whose expression was upregulated in the Yuanbao chicken. Overexpression of BMP10 induced a significant decrease in body length by inhibiting angiogenic vessel development in zebrafish. In addition, three other loci on chromosomes 1, 2, and 24 were also identified to be potentially involved in the development of body size. Our results provide a paradigm shift in identification of novel loci controlling body size variation, availing a fast and efficient strategy. These loci, particularly BMP10, add insights into ongoing research of the evolution of body size under artificial selection and have important implications for future chicken breeding.

NG2-expressing neural progenitors can produce neurons in the central nervous system, providing a potential cell resource of therapy for neurological disorders. However, the mechanism underlying neuronal differentiation of NG2 cells remains largely unknown. In this report, we found that a thrombospondin (TSP) family member, TSP4, is involved in the neuronal differentiation of NG2 cells. When TSP4 was overexpressed, NG2 cells underwent spontaneous neuronal differentiation, as demonstrated by the induction of various neuronal differentiation markers such as NeuN, Tuj1, and NF200, at the messenger RNA and protein levels. In contrast, TSP4 silencing had an opposite effect on the expression of neuronal differentiation markers in NG2 cells. Next, the signaling pathway responsible for TSP4-mediated NG2 cell differentiation was investigated. We found that ERK but not p38 and AKT signaling was affected by TSP4 overexpression. Furthermore, when ERK signaling was blocked by the inhibitor U0126, the neuronal marker expression of NG2 cells was substantially increased. Together, these findings suggested that TSP4 promoted neuronal differentiation of NG2 cells by inhibiting ERK/MAPK signaling, revealing a novel role of TSP4 in cell fate specification of NG2 cells.

Bovine spongiform encephalopathy (BSE), which has been documented in 190,000 cases of BSE-infected cattle, to our knowledge, has not been reported in buffalo. Prion protein (PrP) is critical to susceptibility and development of BSE. Moreover, a new PrP-like protein, Shadoo (Sho), has been shown to have overlapping expression patterns and shared functions with PrP. Therefore, we hypothesize that differences in expression at the transcriptional level and/or the post-transcriptional level of the two genes may be associated with these specific differences between cattle and buffalo. We compared the relative mRNA expression of the prion protein gene (PRNP) and the Shadoo gene (SPRN) in 396 RNA samples using real-time PCR. We also analyzed PrP/Sho protein from 96 samples by Western blot. Our results demonstrated significantly lower PrP expression in the cerebellum, obex, mesenteric lymph node, and bronchial lymph node tissues, but higher relative expression of Sho in the cerebrum and spleen in buffalos compared with cattles. Although these results support our primary assumption, Sho and PrP expressions did not correlate with corresponding mRNA expression, suggesting that the biological modulations of both PrP and Sho proteins are at post-translational levels. Moreover, positive correlations between PRNP and SPRN were found in cattle and buffalo cerebrum as well as in buffalo obex. Conversely, negative correlations between PrP and Sho were detected in buffalo cerebellum and obex tissues. These findings suggest that additional post-transcriptional studies are warranted to elucidate mechanisms behind prion diseases.

PRKAG2 cardiac syndrome is an autosomal dominant inherited disease resulted from mutations in the PRKAG2 gene that encodes γ2 regulatory subunit of AMP-activated protein kinase. Affected patients usually develop ventricular tachyarrhythmia and experience progressive heart failure that is refractory to medical treatment and requires cardiac transplantation. In this study, we identify a H530R mutation in PRKAG2 from patients with familial Wolff-Parkinson-White syndrome. By generating H530R PRKAG2 transgenic and knock-in mice, we show that both models recapitulate human symptoms including cardiac hypertrophy and glycogen storage, confirming that the H530R mutation is causally related to PRKAG2 cardiac syndrome. We further combine adeno-associated virus-9 (AAV9) and the CRISPR/Cas9 gene-editing system to disrupt the mutant PRKAG2 allele encoding H530R while leaving the wild-type allele intact. A single systemic injection of AAV9-Cas9/sgRNA at postnatal day 4 or day 42 substantially restores the morphology and function of the heart in H530R PRKAG2 transgenic and knock-in mice. Together, our work suggests that in vivo CRISPR/Cas9 genome editing is an effective tool in the treatment of PRKAG2 cardiac syndrome and other dominant inherited cardiac diseases by selectively disrupting disease-causing mutations.