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Peanut (Arachis hypogaea L.) is an important source of edible oil and protein for human nutrition. The quality of peanut seed oil is mainly determined by the composition of fatty acids, especially the contents of oleic acid and linoleic acid. Improving the composition of fatty acids in the seed oil is one of the main objectives for peanut breeding globally. To uncover the genetic basis of fatty acids and broaden the genetic variation in future peanut breeding programs, this study used genome-wide association studies (GWAS) to identify loci associated with target traits and developed diagnostic marker. The contents of eight fatty acid components of the Chinese peanut mini-core collection were measured under four environments. Using the phenotypic information and over one hundred thousand single nucleotide polymorphisms (SNPs), GWAS were conducted to investigate the genetics basis of fatty acids under multi-environments. Overall, 75 SNPs were identified significant trait associations with fatty acid components. Nineteen associations were repeatedly identified in multiple environments, and 13 loci were co-associated with two or three traits. Three stable major associated loci were identified, including two loci for oleic acid and linoleic acid on chromosome A09 [mean phenotypic variation explained (PVE): 38.5%, 10.35%] and one for stearic acid on B06 (mean PVE: 23%). According to functional annotations, 21 putative candidate genes related to fatty acid biosynthesis were found underlying the three associations. The allelic effect of SNP A09-114690064 showed that the base variation was highly correlated with the phenotypic variation of oleic acid and linoleic acid contents, and a cost-effective Kompetitive allele-Specific PCR (KASP) diagnostic marker was developed. Furthermore, the SNP A09-114690064 was found to change the cis-element CAAT (-) in the promoter of ahFAD2A to YACT (+), leading dozens of times higher expression level. The enhancer-like activity of ahFAD2A promoter was identified that was valuable for enriching the regulation mechanism of ahFAD2A. This study improved our understanding on the genetic architecture of fatty acid components in peanut, and the new effective diagnostic marker would be useful for marker-assisted selection of high-oleic peanut breeding. [ABSTRACT FROM AUTHOR]

Currently, injection sites of probes, cannula, and optic fibers in stereotactic neurosurgery are typically located manually. This step involves location estimations based on human experiences and thus introduces errors. In order to reduce localization error and improve repeatability of experiments and treatments, we investigate an automated method to locate injection sites. This paper proposes a localization framework, which integrates a region-based convolutional network and a fully convolutional network, to locate specific anatomical points on skulls of rodents. Experiment results show that the proposed localization framework is capable of identifying and locatin bregma and lambda in rodent skull anatomy images with mean errors less than 300 μm. This method is robust to different lighting conditions and mouse orientations, and has the potential to simplify the procedure of locating injection sites. [ABSTRACT FROM AUTHOR]

Background: Functional dyspepsia (FD) is a common functional gastrointestinal disease, and abdominal pain is one of the main symptoms. The aim of this study was to explore the effects and mechanisms of auricular electro-acupuncture (AEA) on gastric hypersensitivity in a rodent model of FD. Methods: Ten-day-old pups were gavaged with 0.2 ml of 0.1% iodoacetamide daily for 6 days. AEA at the “stomach” point with different parameters or sham-EA was performed on 8-week-old animals. Gastric sensitivity to gastric distention was measured under different conditions. Autonomic functions were assessed from the spectral analysis of heart rate variability (HRV) derived from the electrocardiogram. Naloxone was injected intraperitoneally before AEA to explore the opioid mechanism. Gastric emptying was measured at the end of the study. Results: 1) Gastric sensitivity to gastric distention was higher in the FD rats. AEA with parameters of 0.1s on, 0.4s off, 100Hz, 0.3ms and 0.4–0.5mA, but not other parameters or sham-EA, decreased gastric hypersensitivity in the FD rats. Naloxone did not block the effect of AEA. 2) Lower vagal activity and higher sympathovagal ratio were noted in the FD rats, compared with the controls. AEA increased vagal activity and improved sympathovagal imbalance. Conclusions: AEA ameliorates gastric hypersensitivity in FD rats and this effect may be attributed to the improvement of sympathovagal balance. [ABSTRACT FROM AUTHOR]

Late leaf spot (LLS) is one of the most serious foliar diseases affecting peanut worldwide leading to huge yield loss. To understand the genetic basis of LLS and assist breeding in the future, we conducted quantitative trait locus (QTL) analysis for LLS and three plant-type-related traits including height of main stem (HMS), length of the longest branch (LLB) and total number of branches (TNB). Significant negative correlations were observed between LLS and the plant-type-related traits in multi-environments of a RIL population from the cross Zhonghua 5 and ICGV 86699. A total of 20 QTLs were identified for LLS, of which two QTLs were identified in multi-environments and six QTLs with phenotypic variation explained (PVE) more than 10%. Ten, seven, fifteen QTLs were identified for HMS, LLB and TNB, respectively. Of these, one, one, two consensus QTLs and three, two, three major QTLs were detected for HMS, LLB and TNB, respectively. Of all 52 unconditional QTLs for LLS and plant-type-related traits, 10 QTLs were clustered in five genetic regions, of which three clusters including five robust major QTLs overlapped between LLS and one of the plant-type-related traits, providing evidence that the correlation could be genetically constrained. On the other hand, conditional mapping revealed different numbers and different extent of additive effects of QTLs for LLS conditioned on three plant-type-related traits (HMS, LLB and TNB), which improved our understanding of interrelationship between LLS and plant-type-related traits at the QTL level. Furthermore, two QTLs, qLLSB6-7 and qLLSB1 for LLS resistance, were identified residing in two clusters of NB-LRR—encoding genes. This study not only provided new favorable QTLs for fine-mapping, but also suggested that the relationship between LLS and plant-type-related traits of HMS, LLB and TNB should be considered while breeding for improved LLS resistance in peanut. [ABSTRACT FROM AUTHOR]

Microsatellite or simple sequence repeat (SSR) is one of the most widely distributed molecular markers that have been widely utilized to assess genetic diversity and genetic mapping for important traits in plants. However, the understanding of microsatellite characteristics in Arachis species and the currently available amount of high-quality SSR markers remain limited. In this study, we identified 16,435 genome survey sequences SSRs (GSS-SSRs) and 40,199 expressed sequence tag SSRs (EST-SSRs) in Arachis hypogaea and its wild relative species using the publicly available sequence data. The GSS-SSRs had a density of 159.9–239.8 SSRs/Mb for wild Arachis and 1,015.8 SSR/Mb for cultivated Arachis, whereas the EST-SSRs had the density of 173.5–384.4 SSR/Mb and 250.9 SSRs/Mb for wild and cultivated Arachis, respectively. The trinucleotide SSRs were predominant across Arachis species, except that the dinucleotide accounted for most in A. hypogaea GSSs. From Arachis GSS-SSR and EST-SSR sequences, we developed 2,589 novel SSR markers that showed a high polymorphism in six diverse A. hypogaea accessions. A genetic linkage map that contained 540 novel SSR loci and 105 anchor SSR loci was constructed by case of a recombinant inbred lines F6 population. A subset of 82 randomly selected SSR markers were used to screen 39 wild and 22 cultivated Arachis accessions, which revealed a high transferability of the novel SSRs across Arachis species. Our results provided informative clues to investigate microsatellite patterns across A. hypogaea and its wild relative species and potentially facilitate the germplasm evaluation and gene mapping in Arachis species. [ABSTRACT FROM AUTHOR]

Lysophosphatidic acid acyltransferase (LPAT), which converts lysophosphatidic acid (LPA) to phosphatidic acid (PA), catalyzes the addition of fatty acyl moieties to the sn-2 position of the LPA glycerol backbone in triacylglycerol (TAG) biosynthesis. We recently reported the cloning and temporal-spatial expression of a peanut (Arachis hypogaea) AhLPAT2gene, showing that an increase in AhLPAT2 transcript levels was closely correlated with an increase in seed oil levels. However, the function of the enzyme encoded by the AhLPAT2 gene remains unclear. Here, we report that AhLPAT2 transcript levels were consistently higher in the seeds of a high-oil cultivar than in those of a low-oil cultivar across different seed developmental stages. Seed-specific overexpression of AhLPAT2 in Arabidopsis results in a higher percentage of oil in the seeds and greater-than-average seed weight in the transgenic plants compared with the wild-type plants, leading to a significant increase in total oil yield per plant. The total fatty acid (FA) content and the proportion of unsaturated FAs also increased. In the developing siliques of AhLPAT2-overexpressing plants, the expression levels of genes encoding crucial enzymes involved in de novo FA synthesis, acetyl-CoA subunit (AtBCCP2) and acyl carrier protein 1 (AtACP1) were elevated. AhLPAT2 overexpression also promoted the expression of several key genes related to TAG assembly, sucrose metabolism, and glycolysis. These results demonstrate that the expression of AhLPAT2 plays an important role in glycerolipid production in peanuts. [ABSTRACT FROM AUTHOR]

The usual practice of using a control chart to monitor a process is to take samples from the process with fixed sampling interval (FSI). In this paper, a synthetic control chart with the variable sampling interval (VSI) feature is proposed for monitoring changes in the process mean. The VSI synthetic chart integrates the VSI chart and the VSI conforming run length (CRL) chart. The proposed VSI synthetic chart is evaluated using the average time to signal (ATS) criterion. The optimal charting parameters of the proposed chart are obtained by minimizing the out-of-control ATS for a desired shift. Comparisons between the VSI synthetic chart and the existing , synthetic , VSI and EWMA charts, in terms of ATS, are made. The ATS results show that the VSI synthetic chart outperforms the other type charts for detecting moderate and large shifts. An illustrative example is also presented to explain the application of the VSI synthetic chart. [ABSTRACT FROM AUTHOR]

One hundred and forty-six highly polymorphic simple sequence repeat (SSR) markers were used to assess the genetic diversity and population structure of 196 peanut (Arachis Hypogaea L.) cultivars which had been extensively planted in different regions in China. These SSR markers amplified 440 polymorphic bands with an average of 2.99, and the average gene diversity index was 0.11. Eighty-six rare alleles with a frequency of less than 1% were identified in these cultivars. The largest Fst or genetic distance was found between the cultivars that adapted to the south regions and those to the north regions in China. A neighbor-joining tree of cultivars adapted to different ecological regions was constructed based on pairwise Nei’s genetic distances, which showed a significant difference between cultivars from the south and the north regions. A model-based population structure analysis divided these peanut cultivars into five subpopulations (P1a, P1b, P2, P3a and P3b). P1a and P1b included most the cultivars from the southern provinces including Guangdong, Guangxi and Fujian. P2 population consisted of the cultivars from Hubei province and parts from Shandong and Henan. P3a and P3b had cultivars from the northern provinces including Shandong, Anhui, Henan, Hebei, Jiangsu and the Yangtze River region including Sichuan province. The cluster analysis, PCoA and PCA based on the marker genotypes, revealed five distinct clusters for the entire population that were related to their germplasm regions. The results indicated that there were obvious genetic variations between cultivars from the south and the north, and there were distinct genetic differentiation among individual cultivars from the south and the north. Taken together, these results provided a molecular basis for understanding genetic diversity of Chinese peanut cultivars. [ABSTRACT FROM AUTHOR]

Reduced sensitivity of prostate cancer (PC) cells to radiation therapy poses a significant challenge in the clinic. Activation of epidermal growth factor receptor (EGFR), type 1 insulin-like growth factor receptor (IGF1R), and crosstalk between these two signaling pathways have been implicated in the development of radiation resistance in PC. This study assessed the effects of targeting both receptors on the regulation of radio-sensitivity in PC cells. Specific inhibitors of EGFR and IGF1R, Erlotinib and AG1024, as well as siRNA targeting EGFR and IGF1R, were used to radio-sensitize PC cells. Our results showed that co-inhibiting both receptors significantly dampened cellular growth and DNA damage repair, and increased radio-sensitivity in PC cells. These effects were carried out through synergistic inhibition of homologous recombination-directed DNA repair (HRR), but not via inhibition of non-homologous end joining (NHEJ). Furthermore, the compromised HRR capacity was caused by reduced phosphorylation of insulin receptor substrate 1 (IRS1) and its subsequent interaction with Rad51. The synergistic effect of the EGFR and IGF1R inhibitors was also confirmed in nude mouse xenograft assay. This is the first study testing co-inhibiting EGFR and IGF1R signaling in the context of radio-sensitivity in PC and it may provide a promising adjuvant therapeutic approach to improve the outcome of PC patients to radiation treatment. [ABSTRACT FROM AUTHOR]

One hundred and forty-six highly polymorphic simple sequence repeat (SSR) markers were used to assess the genetic diversity and population structure of 196 peanut (Arachis Hypogaea L.) cultivars which had been extensively planted in different regions in China. These SSR markers amplified 440 polymorphic bands with an average of 2.99, and the average gene diversity index was 0.11. Eighty-six rare alleles with a frequency of less than 1% were identified in these cultivars. The largest Fst or genetic distance was found between the cultivars that adapted to the south regions and those to the north regions in China. A neighbor-joining tree of cultivars adapted to different ecological regions was constructed based on pairwise Nei's genetic distances, which showed a significant difference between cultivars from the south and the north regions. A model-based population structure analysis divided these peanut cultivars into five subpopulations (P1a, P1b, P2, P3a and P3b). P1a and P1b included most the cultivars from the southern provinces including Guangdong, Guangxi and Fujian. P2 population consisted of the cultivars from Hubei province and parts from Shandong and Henan. P3a and P3b had cultivars from the northern provinces including Shandong, Anhui, Henan, Hebei, Jiangsu and the Yangtze River region including Sichuan province. The cluster analysis, PCoA and PCA based on the marker genotypes, revealed five distinct clusters for the entire population that were related to their germplasm regions. The results indicated that there were obvious genetic variations between cultivars from the south and the north, and there were distinct genetic differentiation among individual cultivars from the south and the north. Taken together, these results provided a molecular basis for understanding genetic diversity of Chinese peanut cultivars.

Bladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize multiple cancer cell lines to HCPT treatment, such as prostate and cervical cancer. In this study, we investigated whether genistein could sensitize bladder cancer cell lines and bladder epithelial cell BDEC cells to HCPT treatment, and investigated the possible underlying molecular mechanisms. Genistein could significantly and dose-dependently sensitize multiple bladder cancer cell lines and BDEC cells to HCPT-induced apoptosis both in vitro and in vivo. Genistein and HCPT synergistically inhibited bladder cell growth and proliferation, and induced G2/M phase cell cycle arrest and apoptosis in TCCSUP bladder cancer cell and BDEC cell. Pretreatment with genistein sensitized BDEC and bladder cancer cell lines to HCPT-induced DNA damage by the synergistic activation of ataxia telangiectasia mutated (ATM) kinase. Genistein significantly attenuated the ability of HCPT to induce activation of the anti-apoptotic NF-κB pathway both in vitro and in vivo in a bladder cancer xenograft model, and thus counteracted the anti-apoptotic effect of the NF-κB pathway. This study indicates that genistein could act as a promising non-toxic agent to improve efficacy of HCPT bladder cancer chemotherapy.

Complete understanding of the route of HIV-1 transmission is an important prerequisite for curbing the HIV/AIDS pandemic. So far, the known routes of HIV-1 transmission include sexual contact, needle sharing, puncture, transfusion and mother-to-child transmission. Whether HIV can be vertically transmitted from human sperm to embryo by fertilization is largely undetermined. Direct research on embryo derived from infected human sperm and healthy human ova have been difficult because of ethical issues and problems in the collection of ova. However, the use of inter-specific in vitro fertilization (IVF) between human sperm and hamster ova can avoid both of these problems. Combined with molecular, cytogenetical and immunological techniques such as the preparation of human sperm chromosomes, fluorescent in situ hybridization (FISH), and immunofluorescence assay (IFA), this study mainly explored whether any integrated HIV provirus were present in the chromosomes of infected patients' sperm, and whether that provirus could be transferred into early embryos by fertilization and maintain its function of replication and expression. Evidence showed that HIV-1 nucleic acid was present in the spermatozoa of HIV/AIDS patients, that HIV-1 provirus is present on the patient sperm chromosome, that the integrated provirus could be transferred into early embryo chromosomally integrated by fertilization, and that it could replicate alongside the embryonic genome and subsequently express its protein in the embryo. These findings indicate the possibility of vertical transmission of HIV-1 from the sperm genome to the embryonic genome by fertilization. This study also offers a platform for the research into this new mode of transmission for other viruses, especially sexually transmitted viruses.