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"Dragon's blood" is the name given to a deep red resin obtained from a variety of plant sources. The resin extracted from stems of Dracaena cochinchinensis is one such source of "dragon's blood". It has a reputation for facilitating blood circulation and dispersing blood stasis. In traditional Chinese medicine, this resinous medicine is commonly prescribed to invigorate blood circulation for the treatment of traumatic injuries, blood stasis and pain. Modern pharmacological studies have found that this resinous medicine has anti-bacterial, anti-spasmodic, anti-inflammatory, analgesic, anti-diabetic, and anti-tumor activities, while it is also known to enhance immune function, promote skin repair, stop bleeding and enhance blood circulation. Various compounds have been isolated from the plant, including loureirin A, loureirin B, loureirin C, cochinchinenin, socotrin-4'-ol, 4',7-dihydroxyflavan, 4-methylcholest-7-ene-3-ol, ethylparaben, resveratrol, and hydroxyphenol. The present review summarizes current knowledge concerning the botany, phytochemistry, pharmacological effects, toxicology studies and clinical applications of this resinous medicine as derived from D. cochinchinenesis. [ABSTRACT FROM AUTHOR]

We have compared the melanogenic activities of cultured melanocytes carrying two common TYR alleles as homozygous 192S-402R wild-type, heterozygous and homozygous variant. This includes assays of TYR protein, DOPAoxidase activity, glycosylation and temperature sensitivity of protein and DOPAoxidase levels. Homozygous wild-type strains on average had higher levels of TYR protein and enzyme activity than other genotypes. Homozygous 402Q/Q melanocytes produced significantly less TYR protein, displayed altered trafficking and glycosylation, with reduced DOPAoxidase. However, near wild-type TYR activity levels could be recovered at lower growth temperature. In a sample population from Southeast Queensland, these two polymorphisms were present on four TYR haplotypes, designated as WT 192S-402R, 192Y-402R and 192S-402Q with a double-variant 192Y-402Q of low frequency at 1.9%. Based on cell culture findings and haplotype associations, we have used an additive model to assess the penetrance of the ten possible TYR genotypes derived from the combination of these haplotypes. [ABSTRACT FROM AUTHOR]

Enveloped viruses exploit the endomembrane system to enter host cells. Through a cascade of membrane-trafficking events, virus-bearing vesicles fuse with acidic endosomes and/or lysosomes mediated by SNAREs triggering viral fusion. However, the molecular mechanisms underlying this process remain elusive. Here, we found that UV-radiation resistance-associated gene (UVRAG), an autophagic tumor suppressor, is required for the entry of the prototypic negative-strand RNA virus, including influenza A virus and vesicular stomatitis virus, by a mechanism independent of IFN and autophagy. UVRAG mediates viral endocytic transport and membrane penetration through interactions with the class C vacuolar protein sorting (C-Vps) tethering complex and endosomal glutamine-containing SNAREs [syntaxin 7 (STX7), STX8, and vesicle transport through t-SNARE homolog 1B (Vti1b)], leading to the assembly of a fusogenic frans-SNARE complex involving vesicle-associated membrane protein (VAMP8), but not VAMP7. Indeed, UVRAG stimulates VAMP8 translocation to virus-bearing endosomes. Inhibition of VAMP8, but not VAMP7, significantly reduces viral entry. Our data indicate that UVRAG, in concert with C-Vps, regulates viral entry by assembling a specific fusogenic SNARE complex. Thus, UVRAG governs downstream viral entry, highlighting an important pathway capable of potential antiviral therapeutics. [ABSTRACT FROM AUTHOR]

The use of snow and ice cores as recorders of environmental contamination is particularly relevant for per- and polyfluoroalky substances (PFASs) given their production history, differing source regions and varied mechanisms driving their global distribution. In a unique study perfluoroalkyl acids (PFAAs) were analyzed in dated snow-cores obtained from high mountain glaciers on the Tibetan Plateau (TP). One snow core was obtained from the Mt Muztagata glacier (accumulation period of 1980-1999), located in western Tibet and a second core from Mt. Zuoqiupo (accumulation period: 1996-2007) located in southeastern Tibet, with fresh surface snow collected near Lake Namco in 2010 (southern Tibet). The higher concentrations of ΣPFAAs were observed in the older Mt Muztagata core and dominated by perfluorooctanesulfonic acid (PFOS) (61.4-346 pg/L) and perfluorooctanoic acid (PFOA) (40.8-243 pg/L), whereas in the Mt Zuoqiupu core the concentrations were lower (e.g., PFOA: 37.8-183 pg/L) with PFOS below detection limits. These differences in PFAA concentrations and composition profile likely reflect the upwind sources affecting the respective sites (e.g., European/central Asian sources for Mt Muztagata and India sources for Mt Zuoqiupu). Perfluorobutanoic acid (PFBA) dominated the recent surface snowpack of Lake Namco which is mainly associated with India sources where the shorter chain volatile PFASs precursors predominate. The use of snow cores in different parts of Tibet provides useful recorders to examine the influence of different PFASs source regions and reflect changing PFAS production/use in the Northern Hemisphere. [ABSTRACT FROM AUTHOR]

Background: The fruits and seeds of Alpinia galanga (L.) Willd., Alpinia katsumadai Hayata, Alpinia zerumbet (Pers.) Burtt. & Smith, Amomum kravanh Pierre ex Gagnep., Amomum subulatum Roxb., Amomum tsao-ko Crevost et Lemaire, and Elettaria cardamomum (L.) Maton from Alpinia, Amomum, and Elettaria genera in the Zingiberaceae family are difficult to distinguish between each other. This study aims to identify the seeds of these seven species from Zingiberaceae family based on comparative anatomy of microscopic characteristics. Methods: We compared the morphological structures of seed coats by observing the microscopic characteristics of seeds in transverse sections. We described the macroscopic characteristics of seeds in detail. Results: The seeds of these three genera could not be identified to the species level based on their macroscopic features. However, based on the anatomical features of the seed coat observed in transverse sections, a dichotomous key for these seven species was feasible. Conclusion: Seven species in the Zingiberaceae family could be identified based on comparative anatomy of microscopic characteristics of transverse section of seed. [ABSTRACT FROM AUTHOR]

Rabdosia japonica var. glaucocalyx (Maxim.) Hara, belonging to the Labiatae family, is widely used as an anti-inflammatory and antitumor drug for the treatment of different inflammations and cancers. Aim of the Study. To investigate therapeutic effects and possible mechanism of the flavonoids fraction of Rabdosia japonica var. glaucocalyx (Maxim.) Hara (RJFs) in acute lung injury (ALI) mice induced by lipopolysaccharide (LPS). Materials and Methods. Mice were orally administrated with RJFs (6.4, 12.8, and 25.6mg/kg) per day for 7 days, consecutively, before LPS challenge. Lung specimens and the bronchoalveolar lavage fluid (BALF) were isolated for histopathological examinations and biochemical analysis.The level of complement 3 (C3) in serum was quantified by a sandwich ELISA kit. Results. RJFs significantly attenuated LPS-induced ALI via reducing productions of the level of inflammatory mediators (TNF- α, IL-6, and IL-1 β), and significantly reduced complement deposition with decreasing the level of C3 in serum, which was exhibited together with the lowered myeloperoxidase (MPO) activity and nitric oxide (NO) and protein concentration in BALF. Conclusions. RJFs significantly attenuate LPS-induced ALI via reducing productions of proinflammatory mediators, decreasing the level of complement, and reducing radicals. [ABSTRACT FROM AUTHOR]

As a major tumor suppressor gene, the role of PinX1 in breast cancer and its molecular mechanism remain unclear. In this study, overexpression of PinX1 was generated in 3 breast cancer cell lines, and knockdown of PinX1 was performed in a nontumorigenic breast cell line. The regulation of PinX1 on cell proliferation and cell cycle was observed. A microarray-based lncRNA and mRNA expression profile screening was also performed. We found a lower growth rate, G0/G1 phase arrest, and S phase inhibition in the PinX1 overexpressed breast cancer cells, while a higher growth rate, decreased G0/G1 phase, and increased S phase rate in the PinX1 knocked-down nontumorigenic breast cell. A total of 977mRNAs and 631 lncRNAs were identified as differentially expressed transcripts between PinX1 overexpressed and control MCF-7 cells. Further analysis identified the involvement of these mRNAs in 52 cancer related pathways and various other biological processes. 11 enhancer-like lncRNAs and 25 lincRNAs with their adjacent mRNA pairs were identified as coregulated transcripts. Our results confirmed the role of PinX1 as a major tumor suppressor gene in breast cancer cell lines and provided information for further research on the molecular mechanisms of PinX1 in tumorigenesis. [ABSTRACT FROM AUTHOR]

Convincing epidemiological data suggest an inverse association between cancer and neurodegeneration, including Alzheimer's disease (AD). Since both AD and cancer are characterized by abnormal, but opposing cellular behavior, i.e., increased cell death in AD while excessive cell growth occurs in cancer, this motivates us to initiate the study into unraveling the shared genes and cell signaling pathways linking AD and glioblastoma multiform (GBM). In this study, a comprehensive bioinformatics analysis on clinical microarray datasets of 1,091GBM and 524AD cohorts was performed. Significant genes and pathways were identified from the bioinformatics analyses - in particular ERK/MAPK signaling, up-regulated inGBM and Angiopoietin Signaling pathway, reciprocally up-regulated in AD - connecting GBM and AD (P , 0.001), were investigated in details for their roles in GBM growth in an AD environment. Our results showed that suppression of GBM growth in an AD background was mediated by the ERK-AKT-p21-cell cycle pathway and anti-angiogenesis pathway. [ABSTRACT FROM AUTHOR]

In this article, reversal activities of Euphorbia factor L1 (EFL1) against ABCB1-mediated multidrug resistance (MDR) and apoptosis sensitization in K562/ADR cells are reported. EFL1 decreased the IC50 values of anticancer agents in K562/ADR cells over-expressing ABCB1. However, EFL1 did not affect the IC50 values of anticancer agents in sensitive K562 cells. Additionally, EFL1 increased the intracellular accumulation of rhodamine 123 and doxorubicin in K562/ADR cells without affecting their accumulation in K562 cells. Furthermore, EFL1 sensitized the apoptosis triggered by vincristine in K562/ADR cells via mitochondrial pathway, as confirmed by Annexin V-FITC/PI detection and western blot. At the same time, EFL1 did not influence the apoptosis induced by vincristine in K562 cells. Western blot results showed that EFL1 did not affect the phosphorylation level of AKT and ERK in K562 and K562/ADR cells. Finally, EFL1 did not down-regulate protein expression of ABCB1. [ABSTRACT FROM AUTHOR]

Highlights: [•] The corrosion mechanism of 10# steel in shell-side corrosion medium is displayed. [•] The results of this paper play a guidance role for the practical application in the field of refinery heat exchanger tube. [ABSTRACT FROM AUTHOR]

Accurate ultra-short-term PV power forecasting is essential for the power system with a high proportion of renewable energy integration, which can provide power fluctuation information hours ahead and help to mitigate the interference of the random PV power output. Most of the PV power forecasting methods mainly focus on employing local ground-based observation data, ignoring the spatial and temporal distribution and correlation characteristics of solar energy and meteorological impact factors. Therefore, a novel ultra-short-term PV power forecasting method based on the satellite image data is proposed in this paper, which combines the spatio-temporal correlation between multiple plants with power and cloud information. The associated neighboring plant is first selected by spatial-temporal cross-correlation analysis. Then the global distribution information of the cloud is extracted from satellite images as additional inputs with other general meteorological and power inputs to train the forecasting model. The proposed method is compared with several benchmark methods without considering the information of neighboring plants. Results show that the proposed method outperforms the benchmark methods and achieves a higher accuracy at 4.73%, 10.54%, and 4.88%, 11.04% for two target PV plants on a four-month validation dataset, in terms of root mean squared error and mean absolute error value, respectively. • The spatio-temporal correlation between PV power plants is investigated. • Introduce how to select an appropriate neighboring plant. • Verify the mapping relationship between cloud characteristics of neighboring plants and the power of target plants. • An ultra-short-term PV power forecasting method based on cloud information from neighboring plant is proposed. [ABSTRACT FROM AUTHOR]

[Display omitted] • An ultrafast method is developed to synthesize Cu 2 O octahedrons. • Highly dispersed Cu 2 O octahedrons inlaid in Ni Foam are obtained. • The sample displays superior catalytic activity in both alkaline water/seawater electrolytes. • The sample exhibits good catalytic durability and stability. Development of bifunctional cost-effective and self-supporting electrocatalysts for high-performance water/seawater electrolysis are vital for emerging energy storage and conversion technologies. Herein, an ultrafast strategy is reported to synthesis homogeneous Cu 2 O octahedrons inlaid in Ni foam (oct_Cu 2 O-NF) via spontaneous replacement of Ni with Cu, followed by rapid oxidization of Cu in air. Benefiting from the high dispersion of uniform octahedral structure and strong interaction between Cu 2 O and Ni foam, oct_Cu 2 O-NF displayed a superior activity for both oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) as well as outstanding stability. After assembling oct_Cu 2 O-NF as bifunctional electrodes for alkaline seawater splitting, the electrolyzer exhibited a very small cell voltage of 1.71 V to reach 10 mA cm−2. This brand-new way of ultrafast synthesis for oct_Cu 2 O-NF experimentally confirms the feasibility of Cu-based nanomaterials for efficient water/seawater electrolysis. [ABSTRACT FROM AUTHOR]

Background: The WNT1-inducible signaling pathway protein 3 (WISP3), which belongs to the CCN (cysteine-rich protein 61, connective tissue growth factor, nephroblastoma overexpressed) family, is a secreted cysteine-rich matricellular protein that is involved in chondrogenesis, osteogenesis and tumorigenesis. WISP3 gene mutations are associated with progressive pseudorheumatoid dysplasia (PPD, OMIM208230), an autosomal recessive genetic disease that is characterized by the swelling of multiple joints and disproportionate dwarfism. Methodology/Principal Findings: Four PPD patients from two unrelated Chinese families were recruited for this study. The clinical diagnosis was confirmed by medical history, physical examinations, laboratory results and radiological abnormalities. WISP3 mutations were detected by direct DNA sequence analysis. In total, four different mutations were identified, which consisted of two missense mutations, one deletion and one insertion that spanned exons 3, 5 and 6 of the WISP3 gene. One of the missense mutations (c.342T>G/p.C114W) and a seven-base pair frameshift deletion (c.716_722del/p.E239fs*16) were novel. The other missense mutation (c.1000T>C/p. S334P) and the insertion mutation (c.866_867insA/p.Q289fs*31) had previously been identified in Chinese patients. All four cases had a compound heterozygous status, and their parents were heterozygous carriers of these mutations. Conclusions/Significance: The results of our study expand the spectrum of WISP3 mutations that are associated with PPD and further elucidate the function of WISP3. [ABSTRACT FROM AUTHOR]

Drug resistance has always been one of the most important impediments to global malaria control. Artemisinin resistance has recently been confirmed in the Greater Mekong Subregion (GMS) and efforts for surveillance and containment are intensified. To determine potential mechanisms of artemisinin resistance and monitor the emergence and spread of resistance in other regions of the GMS, we investigated the in vitro sensitivity of 51 culture-adapted parasite isolates from the China-Myanmar border area to four drugs. The 50% inhibitory concentrations (IC50s) of dihydroartemisinin, mefloquine and lumefantrine were clustered in a relatively narrow, 3- to 6-fold range, whereas the IC50 range of artesunate was 12-fold. We assessed the polymorphisms of candidate resistance genes pfcrt, pfmdr1, pfATP6, pfmdr6 and pfMT (a putative metabolite/drug transporter). The K76T mutation in pfcrt reached fixation in the study parasite population, whereas point mutations in pfmdr1 and pfATP6 had low levels of prevalence. In addition, pfmdr1 gene amplification was not detected. None of the mutations in pfmdr1 and pfATP6 was associated significantly with in vitro sensitivity to artemisinin derivatives. The ABC transporter gene pfmdr6 harbored two point mutations, two indels, and number variations in three simple repeats. Only the length variation in a microsatellite repeat appeared associated with altered sensitivity to dihydroartemisinin. The PfMT gene had two point mutations and one codon deletion; the I30N and N496- both reached high levels of prevalence. However, none of the SNPs or haplotypes in PfMT were correlated significantly with resistance to the four tested drugs. Compared with other parasite populations from the GMS, our studies revealed drastically different genotype and drug sensitivity profiles in parasites from the China-Myanmar border area, where artemisinins have been deployed extensively for over 30 years. [ABSTRACT FROM AUTHOR]

A new family of 60° dendritic di-Pt(II) acceptor tectons have been successfully designed and synthesized, from which a series of novel "three-component" triangular metallodendrimers were prepared via [3 + 3] coordination-driven self-assembly. The structures of newly designed triangular metallodendrimers are characterized by multinuclear NMR (¹H and 31P), ¹H DOSY NMR, mass spectrometry (CSI-TOF-MS), and elemental analysis. The shape and size of all supramolecular dendritic triangles were investigated with PM6 semiempirical molecular orbital methods. [ABSTRACT FROM AUTHOR]

Background: Understanding the pathogenesis of influenza infection is a key factor leading to the prevention and control of future outbreaks. Pandemic 2009 Influenza H1N1 infection, although frequently mild, led to a severe and fatal form of disease in certain cases that make its virulence nature debatable. Much effort has been made toward explaining the determinants of disease severity; however, no absolute reason has been established. Results: This study presents the heterogeneous virulence of clinically similar strains of pandemic 2009 influenza virus in human alveolar adenocarcinoma cells and mice. The viruses were obtained from patients who were admitted in a local hospital in China with a similar course of infection and recovered. The A/Nanchang/8002/2009 and A/Nanchang/8011/2009 viruses showed efficient replication and high lethality in mice while infection with A/ Nanchang/8008/2009 was not lethal with impaired viral replication, minimal pathology and modest proinflammatory activity in lungs. Sequence analysis displayed prominent differences between polymerase subunits (PB2 and PA) of viral genomes that might correlate with their different phenotypic behavior. Conclusions: The study confirms that biological heterogeneity, linked with the extent of viral replication, exists among pandemic H1N1 strains that may serve as a benchmark for future investigations on influenza pathogenesis. [ABSTRACT FROM AUTHOR]

Objectives: Thrombus and secondary thrombosis plays a key role in stroke. Recent molecular imaging provides in vivo imaging of activated factor XIII (FXIIIa), an important mediator of thrombosis or fibrinolytic resistance. The present study was to investigate the fibrin deposition in a thromboembolic stroke mice model by FXIIIa-targeted near-infrared fluorescence (NIRF) imaging. Materials and Methods: The experimental protocol was approved by our institutional animal use committee. Seventy-six C57B/6J mice were subjected to thromboembolic middle cerebral artery occlusion or sham operation. Mice were either intravenously injected with the FXIIIa-targeted probe or control probe. In vivo and ex vivo NIRF imaging were performed thereafter. Probe distribution was assessed with fluorescence microscopy by spectral imaging and quantification system. MR scans were performed to measure lesion volumes in vivo, which were correlated with histology after animal euthanasia. Results: In vivo significant higher fluorescence intensity over the ischemia-affected hemisphere, compared to the contralateral side, was detected in mice that received FXIIIa-targeted probe, but not in the controlled mice. Significantly NIRF signals showed time-dependent processes from 8 to 96 hours after injection of FXIIIa-targeted probes. Ex vivo NIRF image showed an intense fluorescence within the ischemic territory only in mice injected with FXIIIa-targeted probe. The fluorescence microscopy demonstrated distribution of FXIIIa-targeted probe in the ischemic region and nearby microvessels, and FXIIIa-targeted probe signals showed good overlap with immune-fluorescent fibrin staining images. There was a significant correlation between total targeted signal from in vivo or ex vivo NIRF images and lesion volume. Conclusion: Non-invasive detection of fibrin deposition in ischemic mouse brain using NIRF imaging is feasible and this technique may provide an in vivo experimental tool in studying the role of fibrin in stroke. [ABSTRACT FROM AUTHOR]

Introduction: South China has a proven role in the global epidemiology of previous influenza outbreaks due to its dual seasonal pattern. We present the virologic, genetic and clinical characterization of pandemic H1N1 influenza infection (pH1N1) in Shantou and Nanchang, cities in southern China, during the second wave of the 2009-2010 pandemic. Methodology: Nasopharyngeal swabs were collected from 165 individuals with influenza-like illness (ILI) who presented to the hospitals in Shantou and Nanchang. Laboratory diagnosis and characterization was performed by real-time PCR, virus isolation in embryonated chicken eggs, and sequencing. Results: pH1N1 activity was sustained in three different temporal patterns throughout the study period. The overall positivity rate of pH1N1 was 50% with major distribution among young adults between the ages of 13 and 30 years. High fever, cough, expectoration, chest pain, myalgia, nasal discharge and efficient viral replication were observed as major clinical markers whereas a substantial number of afebrile cases (17%) was also observed. Rate of hospitalization and disease severity (39%) and recovery (100%) were also high within the region. Furthermore, severe complications were likely to develop in young adults upon pH1N1 infection. Genetic characterization of the HA and NA genes of pH1N1 strains exhibited homogenous spread of pH1N1 strains with 99% identity with prototypic strains; however, minor unique mutations were also observed in the HA gene. Conclusion: The study illustrates the detailed characteristics of 2009 influenza pandemic in southern parts of China that might help to strategize preparedness for future pandemics and subsequent influenza seasons. [ABSTRACT FROM AUTHOR]

Folate plays a key role in DNA synthesis and methylation. Limited evidence suggests high intake may reduce risks of esophageal cancer overall; however, associations with esophageal cancer subtypes and Barrett's esophagus (BE), a precancerous lesion, remain unexplored. We evaluated the relation between intake of folate, B vitamins, and methyl-group donors (methionine, choline, betaine) from foods and supplements, polymorphisms in key folate-metabolizing genes, and risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE patients without (n = 266) or with (n = 101) dysplasia were compared with population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245) patients were compared with population controls (n = 1507) using multivariable adjusted logistic regression. Increasing intake of folate from foods was associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased risks of ESCC associated with smoking and alcohol consumption. In contrast, high intake of folic acid from supplements was associated with a significantly elevated risk of BE with dysplasia. High intakes of riboflavin and methionine from food were associated with increased EAC risk, whereas increasing betaine intake was associated with reduced risks of BE without (P-trend = 0.004) or with dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin B-12 were associated with increased EAC risk. There were no consistent associations between genetic polymorphisms studied and BE or EAC risk. High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC. [ABSTRACT FROM AUTHOR]

Comparative studies of enzymatic acylation of troxerutin by the alkaline protease from Bacillus subtilis under ultrasound and shaking were carried out in nonaqueous media. Using divinyl dicarboxylates (CH2=CH–OOC–(CH2)n–COO–CH=CH2, n = 2, 3, 4, 7, 8, 11) featuring different chain length as acyl donors, troxerutin was regioselectively acylated at B ethoxyl group, whether under ultrasound or shaking. Ultrasonic treatment increased the reaction rate and led to high conversion. Several factors, such as pre-irradiation on the enzyme, the power and frequency of the ultrasound, operation manner, as well as the length of the acyl donors were investigated. Using enzyme pre-irradiated for 8 h, the conversion of troxerutin was increased to 87.3% compared with 56.3% obtained from the untreated enzyme. Experimental results also showed that continual ultrasound caused greater rate acceleration than interval ultrasound. Powers of 100, 150 and 200 W, frequencies of 40, 80 and 100 kHz all showed significant improvement on the transesterification, with the greatest effect observed at 150 W, 80 kHz. The acceleration effect increased as the chain length of the acyl donors decreased from C13 to C4. [Copyright &y& Elsevier]

OBJECTIVES:Crohn's disease (CD; MIM 266600) is one of the most common forms of inflammatory bowel disease (IBD), and represents a significant burden to health care in developed countries. Our aim was to determine whether a gene in the IBD linkage region on chromosome 19q13, with a role in Paneth cell secretion and T-cell activation, conferred genetic susceptibility to the development of CD.METHODS:In total, 792 CD cases and 1,244 controls of Australian origin (Caucasian) were genotyped for seven single-nucleotide polymorphisms (SNPs) in the gene encoding the intermediate conductance calcium-activated potassium channel protein (KCNN4) at 19q13.2. CD cases were phenotyped using the Montreal classification. The replication set comprised an additional 326 CD cases and 951 population-based Caucasian controls. Analysis of the KCNN4 mRNA transcript was carried out using quantitative reverse transcriptase-PCR.RESULTS:KCNN4 SNP rs2306801 was associated with CD (primary P=0.0008, odds ratio (OR) (95% confidence interval (CI)): 0.76 (0.65-0.89); replication P=0.01, OR (95% CI): 0.77 (0.61-0.97). Stratification by disease location identified the association between SNP rs2306801 and ileal CD (P=0.01). Non-inflamed ileal mucosa from CD patients carrying any of the common disease-predisposing NOD2 variants (R702W, G908R, 1007fs) had significantly reduced levels of KCNN4 mRNA expression (P=0.001). KCNN4 protein expression was detected in Paneth cells, and in T cells in inflamed lamina propria.CONCLUSIONS:Our data implicate the role of KCNN4 in ileal CD. The dual roles of KCNN4 in Paneth cell secretion and T-cell activation and also its nature as a potassium channel make it an important and practical therapeutic target. [ABSTRACT FROM AUTHOR]

Background. Age and host genetics are important determinants of malaria severity. Lymphotoxin-a (LTa) has been associated with the development of cerebral malaria (CM) and other severe malaria (SM) syndromes. Mutations in genes regulating LTa production contribute to other acute vascular diseases and may contribute to malaria pathogenesis. Methods. We tested the association between rs7291467, a single-nucleotide polymorphism (SNP) in the LTarelated gene encoding galectin-2 (LGALS2), disease severity, and function in a case-control study of ethnic Highland Papuan adults and children with SM (np380) and asymptomatic malaria-exposed controls (np356) originating from a non-malaria-endemic region but residing in a lowland malaria-endemic area of Papua, Indonesia. Results. The LGALS2 SNP showed a significant association with susceptibility to SM (including CM), in children (odds ratio, 2.02 [95% confidence interval, 1.14-3.57]) but not in adults. In SM, the C allele at rs7291467 was associated with enhanced galectin-2 transcript levels. In a separate group of Tanzanian children originating from a malaria-endemic region, we found preservation of the major ancestral LGALS2 allele and no association with susceptibility to CM. Conclusions. Results suggest differences in the inflammatory contribution to the development of SM between children and adults in the same population and potential differences between individuals originating from malariaendemic and non-malaria-endemic areas. [ABSTRACT FROM AUTHOR]

By investigating the effects of recombinant human IGF-2 (rhIGF-2) on the diopter, axial eye length and the expression of IGF-2 in non-form-deprivation (FD) and FD eyes of guinea pig, we tried to elucidate the relationship between the effects of rhIGF-2 on eye growth and FD in guinea pig. Eighty 3-week-old guinea pigs were included in the study, which were divided into two groups randomly. Group A ( n = 40) was the non-FD group, Thirty-two guinea pigs received intravitreal injections of either 1 ng, 10 ng, 100 ng rhIGF-2 or bovine serum albumin (BSA) to the right eye; eight guinea pigs who received no intravitreal injections served as control. Group B ( n = 40) was the FD group; the right eyes were form-deprived, and received the same disposals as group A. The diopter and the axial eye length of all guinea pigs were measured at day 14. The expression of IGF-2 in the retina was measured by Western blot. After 14 days, FD eyes were high myopia. The axial length of FD eyes was significant for longer than that of non-FD eyes. The expression of IGF-2 in the retina of FD eyes was up-regulated. In non-FD group, there was no significant difference in the diopter and axial eye length among rhIGF-2 injection eyes, BSA injection eyes and control eyes, but the expression of IGF-2 in the retina of 10 ng and 100 ng rhIGF-2 injection eyes was obviously down-regulated. In the FDM (form-deprivation myopia) group, the myopic diopter and axial eye length increased in 10 ng and 100 ng rhIGF-2 injection eyes compared with those in BSA injection eyes and control eyes. The level of IGF-2 expression in the retina of 10 ng and 100 ng rhIGF-2 injection eyes was obviously down-regulated. The diopter and expression of IGF-2 in the retina of rhIGF-2 injection eyes was negatively correlated with the dose of each injection, which was positively correlated with the axial length. RhIGF-2 intravitreous injection does not affect the diopter and axial length in non-FD eyes of guinea pig, while it can induce a significant increase in myopic diopter and axial length of FD eyes. RhIGF-2 can promote the development of FDM on the condition of FD. [ABSTRACT FROM AUTHOR]

Epithelial sodium channels (ENaC) are regulated by protein kinase A, in addition to a broad spectrum of other protein kinases. It is not clear whether cGMP/PKG signaling might regulate ENaC activity. We examined the responses of αβγ-ENaC channels expressed in Xenopus oocytes to 8-(4-chlorophenylthio)-cGMP (8-pCPT-cGMP), a cell-permeable cGMP analog. This compound stimulated human αβγ-ENaC activity in a dose-dependent fashion, but cell-impermeable cGMP had no effect. Similar stimulatory effects of cGMP were observed in oocytes expressing either mouse or rat αβγ-ENaC channels. The identical ion selectivity and aniiloride sensitivity of the 8-pCPT-cGMP-activated currents to those of αβγ-ENaC channels suggest that the cGMP-activated currents are associated with expressed ENaC. The PKGI activator Sp isomer of 3-phenyl-1,N²-etheno-8-bromo-cGMP did not elicit a rise in ENaC current and that the 8-pCPT-cGMP-induced activation of ENaC channels was blocked by incubating oocytes with a PKG inhibitor, but not with other cGMPsensitive kinase inactivators for PKA, MEK, MAP, and PKC. Surprisingly, both site-directed mutation of putative consensus PKG phosphorylation sites and truncation of entire cytosolic NH2- and COOH-terminal tails did not alter the response to 8-pCPT-cGMP. The ENaC-activity was activated to the same extent by 8-pCPT-cGMP in cells in which PKGH expression was knocked down using small interfering RNA. Analog to 8-CPT-cAMP, 8-pCPT-cGMP was capable of activating ENaC in the identical manner in cell-free outside-out patches. We conclude that the rapid upregulation of human αβγ-ENaC activity in oocytes by external 8-pCPT-cGMP and 4-chlorothiolphenol-cAMP depends on the parachlorophenylthiol and the hydroxy groups, and 8-pCPT-cGMP may serve as a novel ENaC ligand in addition to activating PKG signal. [ABSTRACT FROM AUTHOR]

Objective: Clinical trials have investigated phytotherapy (PT) in the treatment of cervical cancer. This study aimed to assess the quality and data of current available trials, to compare the efficacy and safety of conventional therapies (CT) including surgical therapy, radiotherapy, and chemotherapy with that of CT plus PT (CT-PT), and to identify herbs used commonly in clinical trials. Methods: Forty-three (43) electronic databases were searched. The quality of eligible trials was assessed by Jadad's scale, and Revman 5.0 software was used for data syntheses and analyses. Result: (1) Of the 48 potential trials retrieved, 18 trials involving 1657 patients met the inclusion criteria, and two trials were graded as high-quality trials; (2) CT-PT achieved a higher 1-year survival rate (SR, p = 0.0002) and tumor remission rate (TRR, p < 0.0001) than CT alone; (3) PT showed therapeutic effects comparable to those of Western medications in diminishing vesical complications (VC, p < 0.0001) and rectal complications (RC, p = 0.08) caused by CT; (4) top 15 herbs used frequently to improve SR or TRR and to treat VC or RC in the retrieved trials were identified. Conclusions: Adjuvant PT may improve the efficacy and safety of CT in clinical treatments of cervical cancer, although this result needs to be further verified by more high-quality trials. [ABSTRACT FROM AUTHOR]

Endophytic actinobacteria are relatively unexplored as potential sources of novel species and novel natural products for medical and commercial exploitation. Xishuangbanna is recognized throughout the world for its diverse flora, especially the rain forest plants, many of which have indigenous pharmaceutical histories. However, little is known about the endophytic actinobacteria of this tropical area. In this work, we studied the diversity of actinobacteria isolated from medicinal plants collected from tropical rain forests in Xishuangbanna. By the use of different selective isolation media and methods, a total of 2,174 actinobacteria were isolated. Forty-six isolates were selected on the basis of their morphologies on different media and were further characterized by 16S rRNA gene sequencing. The results showed an unexpected level of diversity, with 32 different genera. To our knowledge, this is the first report describing the isolation of Saccharopolyspora, Dietzia, Bkstococcus, Dactylosporangium, Promicromonospora, Oerskovia, Actinocorallia, and Jiangella species from endophytic environments. At least 19 isolates are considered novel taxa by our current research. In addition, all 46 isolates were tested for antimicrobial activity and were screened for the presence of genes encoding polyketide synthetases and nonribosomal peptide synthetases. The results confirm that the medicinal plants of Xishuangbanna represent an extremely rich reservoir for the isolation of a significant diversity of actinobacteria, including novel species, that are potential sources for the discovery of biologically active compounds. [ABSTRACT FROM AUTHOR]

An alkaline bath was developed for electroless deposition of Co–W–P thin films on a copper substrate. Effects of pH values, various concentrations of reducing agent, and different powers of ultrasonic on composition, microstructure, and magnetic properties of the films were investigated. It was found out that higher pH could improve cobalt atomic percentage and reduce amounts of phosphorus and tungsten in the film while larger amounts of NaH2PO2 would decrease the cobalt content but increase the tungsten and phosphors content. The ultrasonic was introduced during the electroless deposition. Few effects of ultrasonic on the cobalt content were observed. X-ray diffraction showed that almost all of the deposited films were crystalline and contained hexagonal cobalt with a preferred crystallographic orientation (002). However, a typical amorphous Co–W–P film, which has smooth surface, and no crystallite with definite grains could be obtained when the concentration of NaH2PO2 in the bath was over 1.2 mol/L. The films with rougher and agglomerate nodular structures would be formed in the bath with a higher pH value. Certain power (60 W, 40 kHz) of ultrasonic could smash the grains and led to the formation of a denser and smoother surface. Cracks appeared at the surface of the film when the ultrasonic power was 150 W. Vibration sample magnetometer results showed that the film with maximum magnetization (600 emu/g) and coercivity (1000 Oe) could be achieved when introducing ultrasonic (60 W, 40 kHz) during the deposition. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Crohn's disease (CD) and ulcerative colitis (UC) are the two most common forms of inflammatory bowel disease (IBD), representing a significant health-care burden. A variant in the autophagy gene ATG16L1 (T300A) has been newly identified as a CD susceptibility locus by genome-wide association. Our aim was to assess the contribution of T300A in determining disease susceptibility and phenotype in two independent Australian IBD cohorts and explore the relationship between T300A and known CD risk factors (NOD2[nucleotide-binding oligomerization domain containing 2] status and smoking). METHODS: In total, 669 CD and 543 UC cases, and 1,244 controls (study 1), 154 CD cases and 420 controls (study 2), and 702 unaffected parents from both groups were genotyped. We conducted case–control and family association analyses, and investigated relationships between T300A and disease subgroups and between NOD2 status and cigarette smoking (CD only). RESULTS: The strong association between CD and T300A was confirmed ( P < 0.001), with a two-fold increase in disease risk associated with the GG genotype (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.49–2.58), while ileal CD risk was almost three-fold (OR 2.73, CI 1.87–4.0). ATG16L1 and NOD2 were found to contribute independently to CD risk. A greater than seven-fold increased CD risk was observed for current smokers with a GG genotype ( vs nonsmoking AA genotype; P < 0.001, OR 7.65, CI 4.21–13.91). A significant inverse association was found between T300A and UC ( P= 0.002). This was strongest for patients with extensive, severe disease. CONCLUSIONS: We confirm the strong association between T300A and CD, specifically ileal subphenotype, and also report the first strong association of this variant with UC. [ABSTRACT FROM AUTHOR]

The structures and stabilities of (Al2O3)~ (n = 1-10 and 30) clusters were studied by means of first principles calculations. The calculated results reveal that the global minima of small (Al2O3)~ (n = 1-5) clusters are cage structures with high symmetries, in which Al and 0 atoms are three- and two-coordinated, respectively, and are linked to neighbors via single bonds. Beyond (A1203)5, we calculated both cage and cage-dimer structures for (Al2O3)~ (n = 6-10), and the results show that, at this size range, cage-dimer structures are more stable than cage structures. Furthermore, an onion-like motif for (A1203)10 was studied, and it is interesting to find that, at this size, the onion structure is more favorable than cage and cage-dimer structures. For large clusters, a shell structure of Al600~ is suggested. Electronic properties and calculations on hydrogen adsorption of these aluminum oxide structures are reported, and we discuss their possible use as hydrogen storage materials. [ABSTRACT FROM AUTHOR]

Five new polycyclic Daphniphyllum alkaloids, macropodumines F (1) and G (2), 17-oxoyuzurimine (3), and macropodumines H (4) and I (5), were isolated from the leaves of D. macropodumMiq., collected in Sichuan Province, China. The structures and relative configurations of the new compounds – as well as of four known, related alkaloids – were elucidated on the basis of in-depth spectroscopic and mass-spectrometric analyses, by chemical derivatization, and by comparison of spectroscopic data with those of known compounds. [ABSTRACT FROM AUTHOR]

We have previously shown that a quantitative-trait locus linked to the OCA2 region of 15q accounts for 74% of variation in human eye color. We conducted additional genotyping to clarify the role of the OCA2 locus in the inheritance of eye color and other pigmentary traits associated with skin-cancer risk in white populations. Fifty-eight synonymous and nonsynonymous exonic single-nucleotide polymorphisms (SNPs) and tagging SNPs were typed in a collection of 3,839 adolescent twins, their siblings, and their parents. The highest association for blue/nonblue eye color was found with three OCA2 SNPs: rs7495174 T/C, rs6497268 G/T, and rs11855019 T/C (P values of 1.02 × 10-61, 1.57 × 10-96, and 4.45 × 10-54, respectively) in intron 1. These three SNPs are in one major haplotype block, with TGT representing 78.4% of alleles. The TGT/TGT diplotype found in 62.2% of samples was the major genotype seen to modify eye color, with a frequency of 0.905 in blue or green compared with only 0.095 in brown eye color. This genotype was also at highest frequency in subjects with light brown hair and was more frequent in fair and medium skin types, consistent with the TGT haplotype acting as a recessive modifier of lighter pigmentary phenotypes. Homozygotes for rs11855019 C/C were predominantly without freckles and had lower mole counts. The minor population impact of the nonsynonymous coding-region polymorphisms Arg305Trp and Arg419Gln associated with nonblue eyes and the tight linkage of the major TGT haplotype within the intron 1 of OCA2 with blue eye color and lighter hair and skin tones suggest that differences within the 5' proximal regulatory control region of the OCA2 gene alter expression or messenger RNA-transcript levels and may be responsible for these associations. [ABSTRACT FROM AUTHOR]

Two new complex polycyclic alkaloids, macropodumines D (1) and E (2), both possessing unprecedented skeletons, along with four known related alkaloids, were isolated from the leaves and barks of Daphniphyllum macropodumMiq. The structures including the relative stereochemistry of new compounds 1and 2were elucidated on the basis of detailed spectroscopic data analysis. [ABSTRACT FROM AUTHOR]

Background: Hereditary defects of tooth dentin are classified into two main groups: dentin dysplasia (DD) (types I and II) and dentinogenesis imperfecta (DGI) (types I, II, and III). Type II DGI is one of the most common tooth defects with an autosomal dominant mode of inheritance. One disease-causing gene, the dentin sialophosphoprotein (DSPP) gene, has been reported for type II DGI. Methods: In this study, we characterized a four-generation Chinese family with type II DGI that consists of 18 living family members, including 8 affected individuals. Linkage analysis with polymorphic markers D4S1534 and D4S414 that span the DSPP gene showed that the family is linked to DSPP. All five exons and exon-intron boundaries of DSPP were sequenced in members of type II DGI family. Results: Direct DNA sequence analysis identified a novel mutation (c.49C→T, p.Pro17Ser) in exon 1 of the DSPP gene. The mutation spot, the Pro17 residue, is the second amino acid of the mature DSP protein, and highly conserved during evolution. The mutation was identified in all affected individuals, but not in normal family members and 100 controls. Conclusion: These results suggest that mutation p.Pro17Ser causes type II DGI in the Chinese family. This study identifies a novel mutation in the DSPP gene, and expands the spectrum of mutations that cause DGI. [ABSTRACT FROM AUTHOR]

A reversed-phase HPLC method has been developed for determination of twelve intact glucosinolates—glucoiberin, glucocheirolin, progoitrin, sinigrin, epiprogoitrin, glucoraphenin, sinalbin, gluconapin, glucosibarin, glucotropaeolin, glucoerucin, and gluconasturtiin—in ten traditional Chinese plants. The samples were extracted with methanol and the extracts were cleaned on an activated Florisil column. A mobile phase gradient prepared from methanol and 30 mmol L−1 ammonium acetate at pH 5.0 enabled baseline separation of the glucosinolates. Glucosinolate detection was confirmed by quadrupole time-of-flight tandem mass spectrometric analysis in negative-ionization mode. Detection limits ranged from 0.06 to 0.36 μg g−1 when 5 g of dried plant was analyzed. Recoveries of the glucosinolates were better than 85% and precision (relative standard derivation, n = 3) ranged from 5.3 to 14.6%. Analysis of the glucosinolates provided scientific evidence enabling differentiation of three pairs of easily confused plants. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

This paper gives a brief introduction to establishing a knowledge-based system for intelligent stamping process planning. Studies on the system’s framework, knowledge model and reasoning mode are introduced. Some key technologies such as the feasibility of the stamping process, an optimal algorithm for blank layout, intelligent strip layout and force calculation are researched. The efficiency of stamping process planning can be improved by the system. [ABSTRACT FROM AUTHOR]

Protein disulfide isomerase (PDI, EC 5.3.4.1) is a chaperone and catalyzes the formation and rearrangement of disulfide bonds in proteins. Domain c-(463–491), containing 18 acidic residues, is an interesting and important C-terminal extension of PDI. In this study, the PDI mutant abb′a′, in which domain c is truncated, was used to investigate the relationship between the C-terminal structure and chaperone function. Reactivation and light-scattering experiments show that both wild-type PDI and abb′a′ interact with lactate dehydrogenase (LDH, EC 1.1.1.27), which tends to self-aggregate during reactivation. The interaction enhances reactivation of LDH and reduces aggregation. According to these results, it seems as if domain c might be dispensable to the chaperone function of PDI. However, abb′a′ is prone to self-aggregation and causes increased aggregation of LDH during thermal denaturation. In contrast, wild-type PDI remains active as a chaperone under these conditions and prevents self-aggregation of LDH. Furthermore, measurements of intrinsic fluorescence and difference absorbance during denaturation show that abb′a′ is much more labile to heat or guanidine hydrochloride denaturation than wild-type PDI. This suggests that domain c is required for the stabilization and maintenance of the chaperone function of PDI under extreme conditions. [ABSTRACT FROM AUTHOR]

BACKGROUND Genetic variation contributes to the risk of developing endometriosis. This review summarizes gene mapping studies in endometriosis and the prospects of finding gene pathways contributing to disease using the latest genome-wide strategies. METHODS To identify candidate-gene association studies of endometriosis, a systematic literature search was conducted in PubMed of publications up to 1 April 2008, using the search terms ‘endometriosis’ plus ‘allele’ or ‘polymorphism’ or ‘gene’. Papers included were those with information on both case and control selection, showed allelic and/or genotypic results for named germ-line polymorphisms and were published in the English language. RESULTS Genetic variants in 76 genes have been examined for association, but none shows convincing evidence of replication in multiple studies. There is evidence for genetic linkage to chromosomes 7 and 10, but the genes (or variants) in these regions contributing to disease risk have yet to be identified. Genome-wide association is a powerful method that has been successful in locating genetic variants contributing to a range of common diseases. Several groups are planning these studies in endometriosis. For this to be successful, the endometriosis research community must work together to genotype sufficient cases, using clearly defined disease classifications, and conduct the necessary replication studies in several thousands of cases and controls. CONCLUSIONS Genes with convincing evidence for association with endometriosis are likely to be identified in large genome-wide studies. This will provide a starting point for functional and biological studies to develop better diagnosis and treatment for this debilitating disease. [ABSTRACT FROM AUTHOR]

The application of genetic association studies to detect mitochondrial variants responsible for phenotypic variation has recently been demonstrated. However, the only power estimates currently available are based on the use of mitochondrial haplogroups, which can only tag a small fraction of the common variation in the mitochondrial genome. Here, power estimates are derived for a SNP-based study design for both disease (case-control) and quantitative trait mapping studies. Power is estimated using simulations based on a collection of publicly available mitochondrial sequences of European origin. The power when testing all common mitochondrial SNPs is shown to be equivalent to that when testing only tagging SNPs, despite the relatively high ratio of tagging SNPs to total SNPs resulting from the tagging of all SNPs with a minor allele frequency greater than 1%. The sample size requirements of mitochondrial genome association studies are compared with that of nuclear whole-genome studies. Remarkably, the trade off between the number of tests being performed and the proportion of phenotypic variance explained for a fixed effect size results in approximately equal sample sizes required for both study types, although the per individual cost for the mitochondrial association study is much less. To test the representation of the sequences used in the power simulations, a sample of 3839 individuals from 1037 Australian families was genotyped for 69 tagging SNPs. The strong concordance in allele frequencies and linkage disequilibrium between the European sequences and the Australian sample indicates that the results presented here are transferable across populations of European descent. [ABSTRACT FROM AUTHOR]

Polymeric carbon nitride is reported to be a promising candidate in environmental catalysis for NO decomposition carried out at elevated temperature. Theoretical calculations support a mechanism where Lewis basic site of g-C3N4can donate electrons to the adsorbed NO, decreasing the bond order of N–O thus facilitating the reaction. [ABSTRACT FROM AUTHOR]

We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 × 10−15). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases. [ABSTRACT FROM AUTHOR]

Fe–N–C catalyst obtained by high temperature pyrolysis is one of the most promising electrocatalysts for non-precious metal oxygen reduction reaction (ORR). However, up to now, the lesser density of active sites results in a substantial performance gap between the Fe–N–C materials and the conventional Pt/C ORR catalysts. Herein, an N-doped mesoporous carbon is employed as the support for the dispersion of poly-m-phenylenediamine. With high specific surface areas of 1526 m2 g−1, the as-prepared Fe–N–C materials show the half-wave potential of 0.89 V and 0.79 V in 0.1 M KOH and 0.5 M H2SO4, respectively. Notably, the superior methanol tolerance, as well as excellent stability, makes our Fe–N–C materials as competitive candidates for oxygen electrochemical catalysis. [ABSTRACT FROM AUTHOR]

The organic moiety of the title compound, C11H18NO5P·2H2O, is zwitterionic. The crystal packing is stabilized by N—H⋯O and O—H⋯O hydrogen bonds. [ABSTRACT FROM AUTHOR]

Oncogene-induced senescence is an anti-proliferative stress response program that acts as a fail-safe mechanism to limit oncogenic transformation and is regulated by the retinoblastoma protein (RB) and p53 tumor suppressor pathways. We identify the atypical E2F family member E2F7 as the only E2F transcription factor potently up-regulated during oncogene-induced senescence, a setting where it acts in response to p53 as a direct transcriptional target. Once induced, E2F7 binds and represses a series of E2F target genes and cooperates with RB to efficiently promote cell cycle arrest and limit oncogenic transformation. Disruption of RB triggers a further increase in E2F7, which induces a second cell cycle checkpoint that prevents unconstrained cell division despite aberrant DNA replication. Mechanistically, E2F7 compensates for the loss of RB in repressing mitotic E2F target genes. Together, our results identify a causal role for E2F7 in cellular senescence and uncover a novel link between the RB and p53 pathways. [ABSTRACT FROM AUTHOR]

The genetic heterogeneity of cancer influences the trajectory of tumor progression and may underlie clinical variation in therapy response. To model such heterogeneity, we produced genetically and pathologically accurate mouse models of common forms of human acute myeloid leukemia (AML) and developed methods to mimic standard induction chemotherapy and efficiently monitor therapy response. We see that murine AMLs harboring two common human AML genotypes show remarkably diverse responses to conventional therapy that mirror clinical experience. Specifically, murine leukemias expressing the AML1/ETO fusion oncoprotein, associated with a favorable prognosis in patients, show a dramatic response to induction chemotherapy owing to robust activation of the p53 tumor suppressor network. Conversely, murine leukemias expressing MLL fusion proteins, associated with a dismal prognosis in patients, are drug-resistant due to an attenuated p53 response. Our studies highlight the importance of genetic information in guiding the treatment of human AML, functionally establish the p53 network as a central determinant of chemotherapy response in AML, and demonstrate that genetically engineered mouse models of human cancer can accurately predict therapy response in patients. [ABSTRACT FROM AUTHOR]