Structural alterations from multiple displacement amplification of a human genome revealed by mate-pair sequencing

Comprehensive identification of the acquired mutations that cause common cancers will require genomic analyses of large sets of tumor samples. Typically, the tissue material available from tumor specimens is limited, which creates a demand for accurate template amplification. We therefore evaluated whether phi29-mediated whole genome amplification introduces false positive structural mutations by massive mate-pair sequencing of a normal human genome before and after such amplification. Multiple displacement amplification led to a decrease in clone coverage and an increase by two orders of magnitude in the prevalence of inversions, but did not increase the prevalence of translocations. While multiple strand displacement amplification may find uses in translocation analyses, it is likely that alternative amplification strategies need to be developed to meet the demands of cancer genomics.     

Differential expression of miR-195 in esophageal squamous cell carcinoma and miR-195 expression inhibits tumor cell proliferation and invasion by targeting of Cdc42

MicroRNAs (miRNA) have played an important role in carcinogenesis. In this study, Agilent miRNA microarray was used to identify differentially expressed miRNAs in esophageal squamous cell carcinoma (ESCC) tissues and miR-195 was downregulated in ESCC compared with normal esophageal tissues. Moreover, Cdc42 was confirmed as target gene of miR-195. Ectopic expression of miR-195 in ESCC cells significantly downregulated Cdc42 by directly binding its 3′ untranslated regions, and induced G1 cell cycle arrest, leading to a significant decrease in cell growth, migration, and invasion in vitro. Therefore, our findings demonstrated that miR-195 may act as a tumor suppressor in ESCC by targeting Cdc42.     

Differential COX-2 induction by viral and bacterial PAMPs: Consequences for cytokine and interferon responses and implications for anti-viral COX-2 directed therapies

Cyclooxygenase 2 (COX)-2 is induced by bacterial and viral infections and has complex, poorly understood roles in anti-pathogen immunity. Here, we use a knock-in luciferase reporter model to image Cox2 expression across a range of tissues in mice following treatment with the either the prototypical bacterial pathogen-associated molecular pattern (PAMP), LPS, which activates Toll-like receptor (TLR)4, or with poly(I:C), a viral PAMP, which activates TLR3. LPS induced Cox2 expression in all tissues examined. In contrast, poly(I:C) elicited a milder response, limited to a subset of tissues. A panel of cytokines and interferons was measured in plasma of wild-type, Cox1^−/− and Cox2^−/− mice treated with LPS, poly(I:C), MALP2 (TLR2/6), Pam3CSK4 (TLR2/1), R-848 (TLR7/8) or CpG ODN (TLR9), to establish whether/how each COX isoform modulates specific PAMP/TLR responses. Only LPS induced notable loss of condition in mice (inactivity, hunching, piloerection). However, all TLR agonists produced cytokine responses, many of which were modulated in specific fashions by Cox1 or Cox2 gene deletion. Notably we observed opposing effects of Cox2 gene deletion on the responses to the bacterial PAMP, LPS, and the viral PAMP, poly(I:C), consistent with the differing abilities of the PAMPs to induce Cox2 expression. Cox2 gene deletion limited the plasma IL-1β and interferon-γ responses and hypothermia produced by LPS. In contrast, in response to poly(I:C), Cox2^−/− mice exhibited enhanced plasma interferon (IFNα,β,γ,λ) and related cytokine responses (IP-10, IL-12). These observations suggest that a COX-2 selective inhibitor, given early in infection, may enhance and/or prolong endogenous interferon responses, and thereby increase anti-viral immunity.     

An electrochemical DNA biosensor based on gold nanorods decorated graphene oxide sheets for sensing platform

A simple electrochemical sensor for sensitive and selective DNA detection was constructed based on gold nanorods (Au NRs) decorated graphene oxide (GO) sheets. The high-quality Au NRs–GO nanocomposite was synthesized via the electrostatic self-assembly technique, which is considered a potential sensing platform. Differential pulse voltammetry was used to monitor the DNA hybridization event using methylene blue as an electrochemical indicator. Under optimal conditions, the peak currents of methylene blue were linear with the logarithm of the concentrations of complementary DNA from 1.0 × 10⁻⁹ to 1.0 × 10⁻¹⁴ M with a detection limit of 3.5 × 10⁻¹⁵ M (signal/noise = 3). Moreover, the prepared electrochemical sensor can effectively distinguish complementary DNA sequences in the presence of a large amount of single-base mismatched DNA (1000:1), indicating that the biosensor has high selectivity.     

Dichomitus hubeiensis sp. nov. and a new record of Dichomitus (Basidiomycota) from China

Dichomitus hubeiensis Hai J. Li & B. K. Cui sp. nov. is described from the Hubei province, central China. It is distinct in the genus by its cream to straw‐yellow pore surface and large pores (1–2 per mm), both inamyloid and indextrinoid skeletal hyphae, presence of cystidioles and dendrohyphidia in the hymenium, more or less ellipsoid basidiospores (10–14 × 5.6–7.0 µm). Dichomitus kirkii originally described from Zimbabwe was found in the Yunan province, it is new to the Chinese fungal flora, and is characterized by its buff‐yellow to cinnamon‐buff pore surface, entire to lacerate pores (1–2 per mm) and large cylindrical basidiospores (20.8–25.0 × 6.8–8.0 µm).     

Detection and evolutionary analysis of soybean miRNAs responsive to soybean mosaic virus

MicroRNAs (miRNA) are a class of non-coding RNAs that have important gene regulatory roles in various organisms. However, the miRNAs involved in soybean’s response to soybean mosaic virus (SMV) are unknown. To identify novel miRNAs and biotic-stress regulated small RNAs that are involved in soybean’s response to SMV, two small RNA libraries were constructed from mock-inoculated and SMV-infected soybean leaves and sequenced. This led to the discovery of 179 miRNAs, representing 52 families, among which five miRNAs belonging to three families were novel miRNAs in soybean. A large proportion (71.5 %) of miRNAs arose from segmental duplication, similar to the process that drives the evolution of protein-coding genes. In addition, we predicted 346 potential targets of these identified miRNAs, and verified 12 targets by modified 5′-RACE analysis. Finally, three miRNAs (miR160, miR393 and miR1510) that are involved in plant resistance were observed to respond to SMV infection. The interaction between miRNAs and resistance-related genes provides a novel mechanism for pathogens to evade host recognition.     

MK-2206 induces cell cycle arrest and apoptosis in HepG2 cells and sensitizes TRAIL-mediated cell death

It has become evident that AKT inhibitors have great potential in cancer treatment. In this study, we investigate the anticancer activity of MK-2206, a novel AKT inhibitor, on HepG2 hepatocellular carcinoma cell, and to show whether MK-2206 enhances the apoptosis-inducing potential of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The cell growth inhibition was evaluated by MTT assay and colony formation assay. Cell cycle distribution was assessed by propidium iodide flow cytometry. Apoptosis was determined by AnnexinV-FITC/PI double staining assay and caspase-9, casapse-7, caspase-3, and PARP cleavage. The results of present study showed that MK-2206-induced G1-phase arrest was associated with a marked decrease in the protein expression of cyclin D1 with concomitant induction of p21 and p27. MK-2206-induced apoptosis was characterized by cleavage of a pro-caspase in a concentration-dependent manner. Moreover, the MAP family kinases p38 kinase and JNK were activated by exposure to MK-2206. SB203580, an p38-specific inhibitor, partially blocked MK-2206-induced death of HepG2 cells and caspase activation. A combination of MK-2206 with TRAIL significantly inhibited growth of TRAIL resistant HepG2 cells. Taken together, our findings provide a new insight to better understand anticancer mechanisms of MK-2206, at least in HepG2 cell. Using of MK-2206 as a potent sensitizer to TRAIL-induced apoptotic cell death offers a promising means of enhancing the efficacy of TRAIL-based HCC treatments.     

狐蝠科3种蝙蝠舌长度及结构比较

为探讨旧大陆食果和食蜜蝙蝠的食性类型不同是否造成其取食器官舌长度及结构的差异,本研究以2种食果蝙蝠犬蝠(Cynopterus sphinx)和棕果蝠(Rousettus leschenaultii)以及1种食蜜蝙蝠长舌果蝠(Eonycteris spelaea)为研究对象,比较了这3个物种间舌的差异.犬蝠、棕果蝠和长舌果蝠伸入直径为2 cm试管的最大舌长度L1(包括伸入试管的吻部和吻部以外的舌长)分别为(29.19±0.52)mm、(35.05±0.82) mm、(49.34±1.64) mm;伸出吻端外部的舌长L3分别为(16.25±0.53)mm、(19.25±0.79) mm、(31.88 ± 1.56) mm;与体重转换后的最大舌长度,即转换L1分别为(8.57±0.17) mm/g1/3、(7.90 ±0.27) mm/g1/3、(12.41 ±0.40) mm/g1/3;与体重转换后的伸出吻端外部的舌长,即转换L3分别为(4.77±0.16) mm/g1/3、(4.34±0.22) mm/g1/3、(8.01 ±0.38) mm/g1/3;与体重转换后的解剖舌长分别为(5.56 ±0.16) mm/g1/3、(5.35 ±0.14) mm/g1/3、(6.65±0.38)mm/g1/3.此5个参数种间比较均差异显著,食蜜类的长舌果蝠的5个参数均显著长于食果类犬蝠和棕果蝠的相应参数.通过比较3种蝙蝠的舌结构发现,长舌果蝠的舌尖尖细且具有毛刷状丝状乳头结构,舌面及两侧凹槽较多;犬蝠和棕果蝠的舌尖钝圆,舌面乳头和凹槽较少而平缓.本文结果表明,旧大陆食蜜蝙蝠与食果蝙蝠在舌长度和舌结构上存在明显差异,可能与捕食行为的差异有关.