Among the variants, the homozygote variant CC genotype of mTOR rs17036508 C>T were associated with higher PCa risk than the wild TT genotypes (adjusted OR = 3.73 (95% CI = 1.75-7.94), P = 0.001). The GT genotype of mTOR rs2295080 G>T was more protective than the TT genotypes (adjusted OR=0.54 (95% CI=0.32-0.91), P=0.020). The distributions of Raptor rs1468033 A>G genotypes differed between cases and controls, especially in subgroups defined by age, BMI, smoking status, and ethnicity. The CT/CC genotypes of AKT2 rs7250897 C>T were associated with an increased risk of PCa, particularly in subgroups of age >71 and BMI >24 kg/m2. These findings suggest that SNPs in the PI3K/AKT/mTOR pathway may contribute to the risk of PCa in Chinese men.In this hospital-based case-control study of 413 prostate cancer (PCa) cases and 807 cancer-free controls, we investigated the role of functional single nucleotide polymorphisms (SNPs) of pivotal genes in the PI3K/AKT/mTOR pathway. We genotyped 17 SNPs in  For Raptor variants, heterozygote genotypes AG of polymorphism rs1468033 A>G were associated with PCa risk compared to genotypes GG (adjusted OR=1.61 (95% CI =1.25-2.06), P <0.001). We also found that rs1468033 A>G was associated with PCa risk . Further analysis of the combined genotypes of these three SNPs and AKT2 rs7250897 C>T showed enhanced PCa susceptibility with increasing numbers of putative high-risk genotypes (Ptrend<0.001) , P = 0.006). Further, the mTOR rs17036508 CC genotypes were associated with increased PCa risk by recessive genetic model for subgroups of age ≤71(adjusted OR=4.75 (95%CI =1.78-12.71), P = 0.002), age >71 (adjusted OR=4.88 (95%CI =1.65-14.38), P = 0.004), BMI ≤24 kg/m2 (adjusted OR=3.20 (95%CI =1.2-8.53), P = 0.02), BMI >24 kg/m2 (adjusted OR=8.11 (95%CI =2.62-25.11), P< 0.001), ever smokers (adjusted OR=6.39 (95%CI =2.46-16.6), P< 0.001), and Uygur population (adjusted OR=5.09 (95%CI =2.2-11.78), P< 0.001). On the contrary, the mTOR rs2295080 GT/GG genotypes were associated with decreased PCa risk by a dominant genetic model in BMI >24 kg/m2 and ever smokers subgroups. However, the mTOR rs2295080 GG genotypes were associated with PCa risk among age subgroups according to the recessive genetic model. For Raptor rs1468033 A>G, AG/AA genotypes were associated with increased PCa risk by the dominant genetic model, particularly in subgroups of age >71(adjusted OR=1.81 (95%CI =1.31-2.48), P = 0.003), BMI >24kg/m2 (adjusted OR=2.02 (95%CI =1.42-2.87), P< 0.001), never smokers (adjusted OR=1.61 (95%CI =1.21-2.30), P = 0.009), ever smokers (adjusted OR=1.58 (95%CI =1.13-2.19), P = 0.068), and Uygur population (adjusted OR=1.66 (95%CI =1.26-2.20), P< 0.001). Furthermore, increased PCa risk was observed by recessive genetic model for the BMI >24 kg/m2 subgroup (adjusted OR=5.13 (95% CI=1.94-13.59), P = 0.001). Increased PCa risk was observed for AKT2 rs7250897 C>T by the dominant genetic model, particularly in subgroups of age >71(adjusted OR=1.83 (95%CI =1.33-2.52), P = 0.002) and BMI >24kg/m2 (adjusted OR=1.58 (95%CI =1.12-2.24), P = 0.010). However, further homogeneity tests showed no difference in risk estimates between subgroups for most strata except age group by mTOR rs17036508 CT/CC genotypes (P=0.032), mTOR rs2295080 GG genotypes (P=0.002), AKT2 rs7250897 CT/CC genotypes (P<0.001) and BMI group by Raptor rs1468033 AA genotypes (P<0.001). The details are shown in Table The mTOR rs17036508 CC and rs2295080 TT, Raptor rs1468033 AG/AA, and AKT2 rs7250897 TT/CT) and four environmental risk factors . Among all 8 factors, the Raptor rs1468033 A>G variant was the best one-factor model. Likewise, interactions between mTOR rs17036508 CC, rs2295080 TT and Raptor rs1468033 AG/AA represented the best three-factor model. Age was the most promising environmental risk factor associated with the four genetic factors. The details are presented in Table We performed the multifactor dimensionality reduction (MDR) analysis by including the genotypes of four significant genetic factors  values at variant prior probability levels for all positive findings Table . Some himTOR rs17036508 CC, mTOR rs2295080 GG/GT, Raptor rs1468033 AG/AA, and AKT rs7250897 TT/CT genotypes were associated with PCa risk, especially in age, BMI, smoker-status, and ethnic subgroups. To the best of our knowledge, this is the first post-GWAS study analyzing associations of these six pivotal genes of PI3K/AKT/mTOR pathway with PCa risk.In the current single institution based case-control study, functional SNPs of six pivotal genes of PI3K/AKT/mTOR pathway were associated with PCa risk. Briefly, the mTOR gene is a critical cellular protein with more than 2651 SNPs reported across the whole region [mTOR rs2295080 GT/GG genotypes protected against PCa risk in Han Chinese populations [mTOR rs2295080 GT/GG genotypes were also observed in esophageal squamous cell carcinoma, gastric carcinoma, and renal cell carcinoma [In vitro and in vivo studies suggested that mTOR rs2295080 T allele probably increased the affinity of special transcription factors to this promoter region and contributed to enhanced mTOR activity [mTOR rs2295080 was linked to eight potential functional variants of mTOR with higher linkage disequilibrium (LD) coefficient >0.8, including rs1064261, rs1074078, rs1135172, rs1883965, rs4845860, rs6540965, and rs6671083. Among these, the variant rs1064261 probably interrupted the exonic splicing enhancer or silencer motif and correlated with neuroendocrine tumors [mTOR, variant rs1883965 was associated with esophageal carcinoma, gastric cancer, and hepatocellular carcinoma [mTOR was located within a miRNA binding site and an exonic splicing enhancer or silencer motif, thereby affecting pre-RNA splicing. The association between rs17036508 and PCa was also observed previously [ANGPTL7), resulting in upregulation of ANGPTL7 by hypoxia in cancer cells, which exerts a pro-angiogenesis effect [mTOR and ANGPTL7 simultaneously.The e region . Howeverulations , 19. Thearcinoma –22. In vactivity . Variante tumors , gastrice tumors , and esoe tumors . Similars effect . Taken tRaptor gene, located in 17q25.3 with 34 exons, regulates responses to nutrient and insulin levels [in vitro and in vivo studies have shown that Raptor acts as a scaffold protein that regulates mTOR-dependent signaling [Raptor gene polymorphisms were associated with increased risk for bladder cancer; physical activity, energy balance and genetic variants in the mTOR pathway co-coordinately influenced bladder cancer risk [Raptor rs1468033 was associated with PCa risk, particularly in subgroups of age, BMI, and smoking status, similar to previous findings. Silico analysis indicated that rs1468033 was found with several potential functional polymorphisms of Raptor gene, including rs2292639, rs499609, rs6565500, and rs9899178. Among these, rs2292639, rs4999609, and rs6565500 were predicted as transfactor binding sites, whereas rs9899178 was predicted as splicing site. It is plausible that these variants modulate the expression of Raptor gene, and affect mTOR activity.The n levels . The Rapignaling . One of cer risk . In thisAKT2 was not known. The different AKT isoforms  play contradictory regulatory roles; for example, AKT1 activation inhibits cell migration whereas AKT2 promotes it [et al. reported that AKT2 rs7254617 increased prostate cancer risk [AKT2 rs7250897 was associated with increased PCa risk by a dominant genetic model in subgroups of age >71and BMI >24kg/m2, indicating that rs7250897 altered AKT2 expression, which subsequently affected synthesis of adipose-related proteins. Since the three variants were far from each other, we postulated that they were associated with carcinogenesis by different mechanisms. These findings need to be further validated.Although mTOR activity was previously implicated in promoting PCa cell invasion, the role of motes it , 32. Manmotes it . Additiomotes it . Recentlcer risk . Also, ain vitro and in vivo experiments are necessary to unravel molecular mechanisms for the genetic associations that we have postulated in this study.There were few limitations in the present study that need to be addressed. First, the limited sample size in our study may have decreased detection of weaker genetic effects in carcinogenesis. Second, information regarding predisposition to PCa was not collected for the analysis and might confuse the stratified positive associations. Third, the case-control study may have inherent selection and information biases. Because of insufficient medical records, we could not perform correlative analyses between stages of PCa and variants of AKT pathway that may have provided more information in PCa carcinogenesis. Moreover, further mTOR leading to PCa susceptibility.In summary, we showed that variants of PI3K/AKT/mTOR signal pathway genes may associate with PCa risk. The combined genotypes of these variants enhanced PCa risk with increasing numbers of putative high-risk genotypes. Moreover, the three-factor model  was the best model to predict PCa risk. In conclusion, our study postulated that the genetic variants may alter the expression and activity of We recruited 413 newly diagnosed PCa cases and 807 frequency-matched cancer-free controls from genetically unrelated Chinese Han and Uygur participants in Xinjiang province between January 2003 and January 2015. The cases were histopathologically confirmed as primary prostate adenocarcinoma at the First Affiliated Hospital of Xinjiang medical University (XJMU). Pathological grades of the PCa were determined by Gleason scores from the radical prostatectomy specimens according to the latest WHO criteria . The recAll subjects were interviewed with a written informed consent. Response rate was 92% and 90% for cases and controls, respectively. The experimental and research protocols were approved by the Institutional Review Board of XJMU.http://www.ncbi.nlm.nih.gov/projects/SNP) and SNPinfo web server (http://snpinfo.niehs.nih.gov/snpfunc.htm). The criteria were: 1) minor allele frequency (MAF) was at least 5% in Chinese populations; 2) SNPs were potentially functional according to SNPinfo prediction platform. Ultimately, 17 potentially functional variants were selected involving mTOR , Raptor , AKT1 , AKT2 , PTEN (rs701848 C>T), and K-ras (rs7312175 A>G) based on the bioinformatics analysis performed with HaploView software 4.2. All these SNPs were genotyped by the TaqMan real-time PCR method as described previously [For the six pivotal genes in PI3K/AKT/mTOR pathway, selection strategy for the potentially functional SNPs was based on the NCBI dbSNP database  to identify the best n-factor interaction model [The multifactor dimensionality reduction (MDR) analysis was conducted by the MDR V2.0 beta 8.2 software (on model . We furt


Pseudomonas resinovorans strain MO-1, which possesses a high ability to oxidize Mn(II), has been isolated from oligotrophic pond sediment. The draft genome sequence consists of 6,252,942 bp and has a G+C content of 63.4%. Strain MO-1 has 5,694 coding sequences, including 13 putative Mn(II) oxidation genes. The extracted DNA was sequenced using a 101-bp paired-end sequencing method with an Illumina HiSeq 2500 platform at Hokkaido System Science Co., Ltd. , obtaining 22,074,708 reads, with approximately 350-fold genome coverage. After the adaptors were trimmed using the Trimmomatic program version 0.36 (mnxG (locus tag PputGB1_2447 under GenBank accession no. CP000926), mcoA (locus tag PputGB1_2665 under GenBank accession no. CP000926) and mopA (locus tag PputGB1_3353 under GenBank accession no. CP000926) of Pseudomonas putida GB-1 (−50)  oxidation genes, much more than the 3 annotated Mn(II) oxidation genes in P. putida GB-1.Two gene families encoding multicopper oxidase (MCO) and heme peroxidase oxidase domains play an important role in Mn(II) oxidation in several MnOB. Of our 5,694 CDSs, 1, 8, and 4 CDSs were identified as being related to Mn(II) oxidation; these were homologous to ida GB-1 , respect-1 (−50) . The higlgorithm  are 82.2P. resinovorans strain MO-1 genome sequence has been deposited in DDBJ/EMBL/GenBank under the accession no. BDMA00000000. The version described in this paper is the first version, BDMA01000000.The


Escherichia coli J53, which is used as a recipient in conjugation experiments and is a laboratory strain derived from E. coli K-12. This genome sequence will help in the development of a comprehensive genetic analysis of conjugative elements.We report here the complete genome sequence of  Escherichia coli J53 is a laboratory mutant of E. coli K-12  and Oxford Nanopore Technologies MinION (R9.4 flow cell) systems. A circular chromosome was obtained by a http://mlst.warwick.ac.uk/mlst/dbs/Ecoli), similar to other E. coli K-12 strains. A genomic comparison against the K-12 reference genome for substrain MG1655 (GenBank accession no. U00096) using progressiveMauve (1A (2 copies), IS5, proB, proA, four tRNAs, a part of prophage CP4-6, and a part of a repetitive extragenic palindromic sequence (REP321) in 7 segments. A total of 57,947 bp of insertions included IS10R (6 copies), rtT small RNA (sRNA), and the lambda prophage (GenBank accession no. J02459), in 8 segments. J53 contained an 825,667-bp inversion block flanked by 2 copies of IS5 between nucleotide positions 3652638 and 4476957 of the MG1655 genome.The complete genome contains a 4,682,574-bp chromosome with a GC content of 50.8%, 4,530 coding sequences, 82 tRNA-coding genes, and 22 rRNA-coding operons. The strain belongs to sequence type 10, as per the Achtman multilocus sequence typing scheme (E. coli K-12 genomes available on the NCBI Assembly resource (https://www.ncbi.nlm.nih.gov/assembly/) as of 9 April 2018 and the J53_AICK draft genome sequence, we made a phylogenetic tree based on core single nucleotide polymorphisms (SNPs) with kSNP3.0 (secA gene, which is associated with azide resistance (Using the 39  kSNP3.0 . The J53E. coli J53 has been deposited in GenBank under accession no. CP028702.The complete sequence of the chromosome of


AbstractGammarus are described and illustrated from Tibetan Plateau. Gammarusaltussp. n. and G.limosussp. n. are characterized by pereopods III–IV with a few short setae and uropod III with marginal spines accompanied by short setae. Gammaruskangdingensissp. n. and G.gonggaensissp. n. are characterized by pereopods III–IV with long straight setae on posterior margins and inner ramus of uropod III 0.4 times as long as outer ramus. Detailed morphological comparisons with related species are discussed. A key to 15 Gammarus species from the Tibetan Plateau and a map of their distributions are provided.Four new species of the genus  PageBreakunderstood, except fishes , Beijing.The specimens were collected along the bank of streams flowing from high mountains with a fine-meshed hand net. Samples were preserved in 95% ethanol in the field and deposited in a -20°C refrigerator for long-term preservation. The body length of each amphipod was recorded by holding the specimen straight and measuring the distance along the dorsal side of the body from the base of the first antenna to the base of the telson. All dissected appendages were mounted in glycerol on slides. Appendages were drawn using a Leica DM2500 compound microscope equipped with a drawing tube. The specimens are lodged in the Taxon classificationAnimaliaORDOFAMILIAGenusFabricius, 1775Gammaruspulex .PageBreakTaxon classificationAnimaliaORDOFAMILIAhttp://zoobank.org/B32F6C92-AEAB-4A62-BD6F-4916FCC73377IZCAS-I-A0061-1), 11.6 mm, Maniganggo Town , Dege County, Sichuan Province, altitude 4000 m, August 12, 2001, collected by Xianjin Peng. Paratype: female (IZCAS-I-A0061-2), 10.1 mm; paratypes: five males and five females (IZCAS-I-A0061-3), same data as holotype.Holotype: male , 11.6 mm., 10.1mm.: second article of palp with two groups of B-setae (a group of B-setae); bases of pereopods V–VII elongated (broad), narrowing distally (posterior margin of pereopods V and VI nearly straight); uropod III with spines accompanied by simple setae on inner margin (uropod III with spines accompanied by plumose setae); and telson with no medial spines on surface .G.sichuanensis Hou, Li & Zheng, 2002 in peduncle of antenna I and II with two or three groups of setae along anterior and posterior margins, and pereopod IV with a few setae on posterior margin. It differs from G.sichuanensis (G.sichuanensis in parentheses) by pereopod III with short setae on posterior margins PageBreakPageBreakof merus and carpus (with long setae on posterior margins of merus and carpus); bases of pereopods V–VII elongated (broad in G.sichuanensis); uropod III with no plumose setae (both rami with plumose setae on inner and outer margins).This species is similar to Taxon classificationAnimaliaORDOFAMILIAhttp://zoobank.org/2883210F-54D8-4945-95C0-9C9DEE5D0DA2IZCAS-I-A0059-1), 11.8 mm, Erdaohe, Kangding County , altitude 2470 m, August 19, 2001, collected by Xianjin Peng. Paratype: female (IZCAS-I-A0059-2), 8.5 mm; paratypes: two males and three females (IZCAS-I-A0059-3), same data as holotype.Holotype: male , 11.8 mm, slender., 8.5 mm. in antenna II peduncle having short setae along anterior and posterior margins, and calceoli ; uropod III inner ramus 0.4 times the length of outer ramus (inner ramus 0.7 times the length of outer ramus); uropod III terminal article of outer ramus longer than adjacent spines .Gamamruskangdingensis sp. n. is similar to G.altus sp. n. in the shape of gnathopods I and II. It differs from G.altus sp. n.  in having pereopods III and IV with long setae on posterior margins (with a few short setae on posterior margins); and inner ramus of uropod III 0.4 times the length of outer ramus (0.3), inner margins of inner and outer rami with a row of plumose setae (with no plumose setae).Taxon classificationAnimaliaORDOFAMILIAhttp://zoobank.org/ED25CC10-321D-44B1-98F3-E2E30CC99286IZCAS-I-A0065-1), 10.0 mm, Hepinggou, Baoxing County , Gongga Mountains, altitude 2110 m, June 15, 2001, collected by Jinzhong Fu and Yuezhao Wang. Paratype: female (IZCAS-I-A0065-2) 8.6 mm; paratypes: two males (IZCAS-I-A0065-3), same data as holotype.Holotype: male , 10.0 mm., 8.6 mm. by antenna II peduncle having long setae along anterior and posterior margins, calceoli absent ; outer ramus of uropod III with a few plumose setae on inner margin, inner ramus with no plumose marginal setae (with a row of plumose setae on inner margins of inner and outer rami); terminal article of uropod III shorter than adjacent spines (longer than adjacent spines).The new species of Gammarusgonggaensis sp. n. is similar to G.emeiensis Hou, Li & Koenemann, 2002 in antenna II peduncle with long setae along anterior and posterior margins, calceoli absent, and pereopods III and IV with long setae on posterior margins. It differs from G.emeiensisG.emeiensis.Gammarusgonggaensis sp. n. differs from G.altus sp. n.  by anternna II peduncle with long setae, calceoli absent ; pereopods III and IV with long setae on posterior margin (with a few short setae); uropod III with plumose setae on inner margin of inner ramus (with no plumose setae), terminal article shorter than adjacent spines (longer than adjacent spines).Taxon classificationAnimaliaORDOFAMILIAhttp://zoobank.org/9ACD4C39-16EC-47AF-A3B0-C32C3BA8EAC3IZCAS-I-A0063-1), 8.6 mm, Baxoi County , Tibet, altitude 4400 m, August 21, 2001, collected by Xianjin Peng. Paratype: female (IZCAS-I-A0063-2), 5.5 mm; paratypes: five males and five females (IZCAS-I-A0063-3), same data as holotype.Holotype: male , 8.6 mm., 5.5 mm. by pereopod III with few setae on posterior margin (merus with four groups of setae on posterior margin); epimeral plate III acute on posterodistal corner (blunt); and uropod III inner ramus longer than half of outer ramus length (inner ramus 0.3 times the length of outer ramus).Gammaruslimosus sp. n. is very similar to G.balcanicus Schäferna, 1922 (widespread in Europe). It differs from the latter by pereopods III–IV and uropod III having few setae; bases of pereopods VI and VII slender.Gammarus recorded from the Tibetan Plateau can be classified into four groups based on morphological comparison: (1) G.lacustris group, is characterized by uropod III inner ramus longer than half of outer ramus length, both rami fringed with plumose setae, and includes five species: G.lacustris Sars, 1863, G.lasaensis Barnard & Dai, 1988, G.hongyuanensis Barnard & Dai, 1988, G.frigidus Hou & Li, 2004, and G.jaspidus Hou & Li, 2004; (2) cave species with no eyes, including G.abstrusus Hou, Platvoet & Li, 2006, and G.praecipuus Li, Hou & An, 2013; (3) G.sinuolatus Hou & Li, 2004 with long simple setae on uropod III; and (4) G.kangdingensis group is characterized by uropod III having a few simple or plumose setae, and includes G.emeiensis Hou, Li & Koenemann, 2002, G.sichuanensis Hou, Li & Zheng, 2002, G.glaber Hou, 2017, Gammarusaltus sp. n., G.kangdingensis sp. n., G.gonggaensis sp. n., and G.limosus sp. n. A key to these species is presented as follows.The species of the genus


MLL) gene produce fusion proteins such as MLL-AF4 that disrupt epigenetic pathways and cause poor-prognosis leukemias. Here, we find that at a subset of gene targets, MLL-AF4 binding spreads into the gene body and is associated with the spreading of Menin binding, increased transcription, increased H3K79 methylation (H3K79me2/3), a disruption of normal H3K36me3 patterns, and unmethylated CpG regions in the gene body. Compared to other H3K79me2/3 marked genes, MLL-AF4 spreading gene expression is downregulated by inhibitors of the H3K79 methyltransferase DOT1L. This sensitivity mediates synergistic interactions with additional targeted drug treatments. Therefore, epigenetic spreading and enhanced susceptibility to epidrugs provides a potential marker for better understanding combination therapies in humans.Understanding the underlying molecular mechanisms of defined cancers is crucial for effective personalized therapies. Translocations of the mixed-lineage leukemia (  •MLL-AF4 binding requires an unmethylated CpG (uCpG) island and Menin•MLL-AF4 and Menin can spread into the gene body of some targets•Spreading targets are highly transcribed and have an aberrant chromatin signature•Spreading of MLL-AF4 is a predictor of sensitivity to DOT1L inhibitors Translocations of the MLL gene produce fusion proteins such as MLL-AF4 that cause poor-prognosis leukemias. Kerry et al. show that MLL-AF4 can spread into the gene body of some target genes. Spreading targets have an aberrant chromatin signature and are sensitive to DOT1L inhibitors. MLL) gene produce over 120 different MLL fusion proteins (MLL-FPs) that cause aggressive acute leukemias, the most common one being the MLL-AF4 fusion  at target genes, an epigenetic mark associated with gene activation . H3K79MeHere, we reveal a strong co-dependent relationship between MLL-AF4 and Menin binding at a small number of target genes containing uCpGs. At a subset of these gene targets, we observe MLL-AF4 and Menin spreading that is bookended by uCpGs. These spreading targets are distinct from super-enhancers, are associated with high levels of gene transcription, have an aberrant H3K79me2/H3K36me3 signature, and are predictive of a poor overall survival in patients with acute lymphoblastic leukemia (ALL). These gene targets also display a remarkable dependence on H3K79me2 and the fusion protein for their sustained expression in leukemia. Together, this work shows that MLL-FP spreading occurs at genes important in MLL leukemogenesis and has the potential to act as a biomarker for therapeutic response.Using MLL(N) and AF4(C) chromatin immunoprecipitation sequencing (ChIP-seq) in the human MLL-AF4 SEM cell line C, we ideIf the CXXC domain is essential for MLL-AF4 recruitment, we would expect all MLL-AF4 binding sites to occur at regions of uCpGs. To test this, we used a biotinylated CXXC affinity purification (Bio-CAP) assay  for highTo determine whether other CXXC domain-containing proteins (“CXXC proteins” from now on) are also restricted to only a proportion of uCpG sites, we performed ChIP-seq for CFP1 (a CXXC protein member of the SET1 complex associated with gene activation), and KDM2B (a CXXC protein involved in the recruitment of the polycomb group repressive complex [PRC] ), in SEM2 = 0.96)  I, wherea = 0.96) J and S1HChIP-seq on two members of PAFc, PAF1 and LEO1 C, overlaLedgf siRNA  system see A legend gf siRNA F and S2GNA level F.HOXA9 locus  gene target isoforms  ChIP-seq in the MLL-AF6 cell line ML-2 detects the fusion protein unambiguously due to a deletion of the wild-type isoforms , and simisoforms B. The hiisoforms . ER-taggisoforms , biotin-isoforms , MLL-AF4isoforms , MLL-AF4, at wild-type MLL binding sites in SEM cells C and 4D,ARID2, JMJD1C, MBNL1, MEF2C, or RUNX2 alone is associated with at least one indicator of poor prognosis in ALL patients .Cell lines, culture methods, and drug treatment protocols used in this study are listed in Western blot analysis was performed as previously described . AntibodChIP and ChIP-seq experiments were performed as described in MLL-AF4, Menin, and PAF1 cDNA were inserted downstream of the FS2-TetR coding sequence in the original pCAGFS2TetR vector, by ligation-independent cloning (LIC). Plasmids were transfected into TetO mESCs using Lipofectamine 2000, and clones stably expressing TetR fusions were selected using puromycin (1 μg/mL), or MLL-AF4 cDNA was transiently transfected into mESCs at 60%–70% confluency using Lipofectamine 2000. Cells were collected 24 hr after transfection.For the TetR recruitment assay, we used the previously engineered Tet-operon (TetO) mESC line . MLL-AF4ChIP-seq peaks were called as described in Nascent RNA-seq and gene expression analysis was performed as described in Clinical datasets and survival analyses are detailed in GSE13313, GSE28460, GSE29130, GSE34861, GSE73528, GSE74812, and GSE84116; and ArrayExpress: E-MTAB-3593 (for a detailed list of datasets, see Data were analyzed using Fisher’s exact test, Wilcoxon test, and Mann-Whitney U test, where appropriate. Results were deemed significant if p < 0.05. Unless otherwise indicated, data are shown as mean ± SD. This paper analyzed datasets from GEO: Conceptualization, T.A.M. and J.K.; Formal analysis, J.K., E.R., H.G., and H.M.; Investigation, J.K., L.G., M.T., N.P.B., H.M., E.B., T.A.M.; Resources, S.O., F.P., O.H., A.R., I.R.; Writing – Original draft, T.A.M. and J.K.; Writing – Review & Editing, T.A.M., J.K., O.H., A.R., I.R., M.K., R.J.K., H.G.; Visualization, T.A.M. and J.K.; Supervision, T.A.M., M.K., and R.J.K.; Funding Acquisition, T.A.M., O.H., A.R., I.R., R.J.K., M.K.


Riemerella anatipestifer, the tetracycline susceptibility of 212 R. anatipestifer isolates from China between 2011 and 2017 was tested. The results showed that 192 of 212 (90.6%) R. anatipestifer isolates exhibited resistance to tetracycline (the MICs ranged from 4 to 256 μg/ml). The results of PCR detection showed that, 170 of 212 (80.2%) R. anatipestifer isolates possessed the tet(X) gene. Other genes, including tet(A), tet(M), tet(Q), tet(O), tet(B), and tet(O/W/32/O), were found at frequencies of 20.8, 4.7, 1.4, 0.9, 0.9, and 0.5%, respectively. However, tet(C), tet(E), tet(G), tet(K), and tet(W) were not detected in any isolate. In these tet gene positive strains, 31 (14.6%), 2 (0.9%), 5 (2.4%), 1 (0.5%), 3 (1.4%) were detected containing tet(A)/tet(X), tet(M)/tet(O), tet(M)/tet(X), tet(O)/tet(X), and tet(Q)/tet(X) simultaneously, respectively. One isolates, R131, unexpectedly contained three tet genes, i.e., tet(M), tet(O), and tet(X). Sequence analysis of the tet gene ORFs cloned from R. anatipestifer isolates confirmed that tet(A), tet(B), tet(M), tet(O), tet(Q) and an unusual mosaic tet gene tet(O/W/32/O) were present in R. anatipestifer. The MIC results of R. anatipestifer ATCC 11845 transconjugants carrying tet(A), tet(B), tet(M), tet(O), tet(O/W/32/O), tet(Q), and tet(X) genes exhibited tetracycline resistance with MIC values ranging from 4 to 64 μg/ml. Additionally, the tet(X) gene could transfer into susceptible strain via natural transformation (transformation frequencies of ~10−6). In conclusion, the tet(A), tet(B), tet(M), tet(O), tet(O/W/32/O), tet(Q), and tet(X) genes were found and conferred tetracycline resistance in R. anatipestifer isolates. Moreover, the tet(X) is the main mechanism of tetracycline resistance in R. anatipestifer isolates. To our knowledge, this is the first report of tet(A), tet(B), tet(M), tet(O), tet(Q), and mosaic gene tet(O/W/32/O) in R. anatipestifer.To investigate tetracycline resistance and resistant genotype in  In addition, an unknown gene tet(U) was reported to be located on the pKq10 plasmid in Enterococcus faecium  gene was reported to be located on the pRA0511 plasmid in R. anatipestifer  was reported to be the main mechanism of tetracycline resistance in R. anatipestifer isolates , tet(B), tet(O), tet(O/W/32/O), tet(Q) in R. anatipestifer and their resistant function were confirmed by transferring into tetracycline-susceptible R. anatipestifer ATCC 11845.To determine the tetracycline resistance mechanisms of R. anatipestifer field isolates were isolated from 58 large-scale duck farms in different regions of China between 2011 and 2017, including Sichuan, Jiangsu, Guizhou, Anhui, Guangdong, Chongqing, Guangxi, Hainan, Jiling, Henan and Beijing provinces. Under sterile conditions, the brains, hearts or livers were collected from infected or died ducks, and samples were streak-inoculated on tryptic soybean agar plates  supplementary with 10% sheep-blood. A single colony from one duck was purified and cultured repeatedly. A total of 212 isolates were identified as R. anatipestifer by PCR amplifying 16S rRNA and sequencing and biochemical analyses. R. anatipestifer strains were cultured at 37°C in GC broth (GCB) or on GC agar (GCA) plates  strains DH5α and S17-1 were grown at 37°C in Luria-Bertani  broth or on LB agar. When required, antibiotics were added as follows: 5 μg/ml tetracycline (TET); 2 μg/ml cefoxitin (FOX); 40 μg/ml kanamycin (KAN) or 100 μg/ml ampicillin (AMP). All antibiotics were obtained from Dalian Meilun Biotech Co., Ltd. .The bacteria and plasmids used in this study are listed in Table 6 CFU/ml (100 μl/well). The inoculated micro-plates were incubated at 37°C for 24 h. E. coli ATCC 25922 was used as a quality control strain. The experiments were repeated at least three times. Due to the lack of CLSI-approved tetracycline breakpoints applicable to R. anatipestifer  in 96-well microtiter-plates  according to Clinical and Laboratory Standards Institute (CLSI) guideline specific for bacteria isolated from animals CLSI, . The finp. CLSI, , i.e., stet) characterized previously in other bacteria were determined in all R. anatipestifer field isolates by PCR , tet(B), tet(C), tet(E), tet(G), tet(K)], 4 ribosomal protection genes , enzymatic inactivation gene tet(X), and a mosaic tetracycline resistance gene tet(O/W/32/O). The primers and protocols described previously  was used as positive control. Since the absence of available positive controls for other tet genes, all PCR products were size-confirmed by electrophoresis on a 1.5% agarose gel. All amplicons of tet(B), tet(M), tet(O), tet(O//W/32/O), and tet(Q) from R. anatipestifer isolates were verified by sequencing , while only 12 amplicons of tet(A) were sequenced.The PCR templates were prepared by treating the bacteria with lysis buffer  and boiled for 10 min. The presence of the tetracycline resistance genes (tet(X) gene was amplified by PCR from R. anatipestifer CH-2 using the primer sets tet(X)-F2/tet(X)-R2, listed in Table tet(A), tet(B), tet(M), tet(O), tet(O/W/32/O), and tet(Q) gene were also amplified from tet-positive isolates confirmed above using the additional primers that were designed based on the previously described tet sequences in other bacteria (Table tet(A), tet(B), tet(M), tet(O), tet(O/W/32/O), and tet(Q) genes, respectively. The purified amplicons were sequenced and digested with restriction enzymes, and then ligated to the same digested shuttle vector pLMF03  and KAN (40 μg/ml) and identified by PCR. At the same time, the negative control empty vector pLMF03 was transferred into ATCC 11845, resulting in the transconjugant ATCC 11845 (pLMF03). The MICs of tetracycline for the wild-type and transconjugants were measured as described above.The correct recombinant plasmids were transferred into tet(X) gene was verified by natural transformation as described previously  were respectively used as donor DNA and transferred into the recipient strain R. anatipestifer ATCC 11845. The transformants, designated ATCC 11845 [tet(X)], were screened using GCB plates supplemented with TET (5 μg/ml). The insertion of the transferred tet(X) genes was verified by PCR and sequencing. The tetracycline resistance phenotypes of transformant was determined as described above.The transferability of the tet(A), tet(B), tet(M), tet(O), tet(O/W/32/O), and tet(Q) genes in R. anatipestifer isolates R100, R98, R131, R96, and R159 in this study have been deposited in GenBank under the accession numbers from MF969099 to MF969104, respectively.The sequences of All animals studies were conducted in strict accordance with the recommendations of the Guide for the Care and Use of Laboratory Animals, National Research Council. The animal-use procedures were approved by the Animal Ethics Committee of the Sichuan Agricultural University .R. anatipestifer field isolates were resistance to tetracycline by susceptibility test. The MICs of tetracycline in 212 R. anatipestifer field isolates ranged from 0.25 to 256 μg/ml  was detected in 170 of 212 isolates, exhibiting the highest rate of occurrence among tet genes (80.2%). The detected frequency of other tet genes was as followed: tet(A) (20.8%), tet(M) (4.7%), tet(Q) (1.4%), tet(O) (0.9%), tet(B) (0.9%), and tet(O/W/32/O) (0.5%). However, tet(C), tet(E), tet(G), tet(K), and tet(W) were not detected in any of 212 tested R. anatipestifer field isolates (Table tet genes simultaneously (Table tet(X) was detected simultaneously along with tet(A), tet(M), tet(O), and tet(Q) in 31(14.6%), 5 (2.4%), 1 (0.5%), and 3 (1.4%) isolates, respectively. Two isolates (0.9%) carried tet(M) and tet(O) genes simultaneously. Moreover, one isolate (0.5%) had three commensal tet genes, tet(M), tet(O), and tet(X), respectively. The R. anatipestifer field isolates containing one or more tet genes exhibited tetracycline resistance with MICs ranging from 4 to 256 μg/ml, while no tet genes were detected in 19 tetracycline-susceptible isolates and 1 intermediately resistant isolate. Although several isolates carried more than one tet genes in this study, they did not display higher MIC values. Thus, the positive rate of genotype was in line with that of tetracycline resistance phenotype.To assess the prevalence of the R. anatipestifer isolates selected for ORFs sequencing were listed in Table tet(A) gene cloned from six different R. anatipestifer isolates shared 99–100% identity (Table MF969099) showed 99% sequence identity with the tet(A) gene from transposon Tn1721  gene cloned from R. anatipestifer isolates showed 99% identity each other. The one in R98 isolate (GenBank accession no. MF969100) showed 100% identity with tet(B) gene from transposon Tn10  genes from five different R. anatipestifer isolates shared 99–100% sequence homology. The one in R133 isolate (GenBank accession no. MF969101) exhibited 96 and 95% sequence identity with tet(M) genes from Streptococcus pneumoniae  genes cloned from R. anatipestifer isolates were 100% identity. The tet(O) gene in R131 isolate (GenBank accession no. MF969102) exhibited 99% sequence identity with the tet(O) genes from Streptococcus mutans DL5  from R. anatipestifer isolate R96 (GenBank accession no. MF969103) was a mosaic tetracycline resistance gene derived from tet(O) and tet(W) genes. Sequence alignment result showed that it had 97 and 99% sequence identity with the tet(W/32/O) gene from Bifidobacterium thermophilum (GenBank accession no. AM710601)  gene from Streptococcus suis integrative conjugative element ICESsu32457 (GenBank accession no. FR823304)  gene from three different R. anatipestifer isolates shared 100% identity. The tet(Q) gene in R159 isolate (GenBank accession no. MF969104) exhibited 97% sequence identity with the tet(Q) gene from Bacteroides thetaiotaomicron  gene in R. anatipestifer CH-2  gene previously reported on the pRA0511 plasmid in R. anatipestifer , tet(B), tet(M), tet(O), tet(O/W/32/O), tet(Q), and tet(X) genes were responsible for tetracycline resistance in R. anatipestifer, recombinant plasmids carrying these genes amplified from different R. anatipestifer isolates were transferred into the tetracycline-susceptible R. anatipestifer ATCC 11845 by conjugative transfer. The tetracycline MICs for all transconjugants ranged from 4 to 64 μg/ml (Table tet(A), tet(B), or tet(O) genes showed low-level tetracycline resistance, and their MIC values were 4–8 μg/ml. The transconjugants containing tet(M), tet(O/W/32/O), or tet(X) genes exhibited tetracycline resistance of 32 μg/ml. The tetracycline resistance of ATCC 11845 [pLMF03-R159-tet(Q)] was the highest among all transconjugants .To further verify whether the identified tet(X) gene, we transferred the tet(X) gene from R. anatipestifer CH-2 to ATCC 11845 by natural transformation. The results showed that the tet(X) gene could be successfully transferred into tetracycline-susceptible ATCC 11845. The maximum transformants were obtained with transformation frequency about ~10−6 for 5 μg R. anatipestifer CH-2 genome. Compared with wild-type strain ATCC11845, the transformant ATCC 11845 [tet(X)] exhibited 128-fold increased tetracycline resistance  gene could confer tetracycline resistance and be easily transferred by natural transformation in R. anatipestifer.To study the transferability of the R. anatipestifer isolates in China. The results of antimicrobial susceptibility showed that tetracycline resistance in R. anatipestifer was widespread in China between 2011 and 2017, although the usage of this antibiotic treatment was decreased in the avian industry. By PCR detection, the genotypes of tetracycline resistance were abundant in our investigated R. anatipestifer isolates, including efflux genes [tet(A) and tet(B)], ribosomal protection genes , enzymatic gene tet(X), and mosaic tetracycline resistance gene tet(O/W/32/O). The total rate of positive resistance genes was as high as 90.6%. The tet(X) gene had the highest occurrence frequency and was the dominant mechanism conferring tetracycline resistance in R. anatipestifer isolates. Unexpectedly, this conclusion was in contrast to previous reports that ribosomal protection and efflux pumps were the classical tetracycline resistance mechanisms in other bacteria  detected in this study was also in contrast to the previous conclusion that tet(C) was the main mechanism of tetracycline resistance in R. anatipestifer isolates , tet(A), tet(B), tet(M), tet(O), tet(O/W/32/O), and tet(Q) genes were detected in R. anatipestifer.Tetracyclines have been widely used for disease treatment and growth promotion in livestock Roberts, . In thistet genes or an isolate may contain different tet genes on different plasmids or some tet genes on plasmid and other tet genes in the chromosome  or tet(S) gene was reported to accompany with tet(M) gene /tet(B), tet(A)/tet(C), and tet(A)/tet(D)] /tet(C), and tet(C)/tet(M)]. In this study, multiple tet genes were also found in one R. anatipestifer isolate, such as tet(A)/tet(X), tet(M)/tet(O), tet(M)/tet(X), tet(O)/tet(X), tet(Q)/tet(X), and tet(M)/tet(O)/tet(X). This phenomenon might be due to strong selective pressure and horizontal gene transfer among the various bacteria , the tet(X), tet(A), tet(B), tet(M), tet(O), tet(O/W/32/O), and tet(Q) genes were most likely located in the chromosome of R. anatipestifer. We confirmed that the tet(X) gene could be transferred by natural transformation, and this transferability might contribute to its wide dissemination in R. anatipestifer.The Roberts, . In genetet(A), tet(B), tet(M), tet(O), tet(O/W/32/O), tet(Q), and tet(X) genes to susceptible strain, we verified that all tet(A), tet(B), tet(M), tet(O), tet(O/W/32/O), tet(Q), and tet(X) genes were functional and conferred tetracycline resistance in R. anatipestifer. Interestingly, tet genes detected in this study have high identities with others reported previously, while they exhibited comparatively lower tetracycline resistance in R. anatipestifer , tet(B), and tet(O) conferred the tetracycline resistance with the MIC values from 4 to 8 μg/ml. We speculated that the low-level of resistance in R. anatipestifer might result from the low-level of tet gene expression, which needed to be further illustrated.Finally, through transferring the tet(A), tet(B), tet(M), tet(O), tet(O/W/32/O), and tet(Q) tetracycline resistance genes in R. anatipestifer. We confirmed that all the tet(A), tet(B), tet(M), tet(O), tet(O/W/32/O), tet(Q), and tet(X) confer the tetracycline resistance in R. anatipestifer. The predominant tetracycline resistance mechanism in R. anatipestifer is conferred by tet(X) gene.To the best of our knowledge, this is the first report of the presence of tet genes in R. anatipestifer isolates. D-KZ, X-XZ, and R-YJ cloned and sequenced the tet genes. SC, K-FS, and QY analyzed the sequences of tet genes. H-YL, YW, and X-YC transferred the shuttle vectors. D-KZ, H-YL, and M-SW performed the natural transformation of tet(X) gene. HL, D-KZ, and A-CC drafted and revised the manuscript. All authors have read and approved the final version of the manuscript.D-KZ, M-SW, and A-CC conceived and designed the project. H-YL, M-FL, and M-SW performed the tetracycline susceptibility test and prevalence of The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Case Reports in Psychiatry has retracted the article titled “Combined Case of Blood-Injury-Injection Phobia and Social Phobia: Behavior Therapy Management and Effectiveness through Tilt Test” . The artHeimberg RG et al.: Psychometric properties of the Liebowitz Social Anxiety Scale. Psychological Medicine, 1999, 29, 199–212 (not cited);Ayala ES, Meuret AE, Ritz T: Treatments for blood-injury-injection phobia: a critical review of current evidence. J Psychiatr Res. 2009 Oct; 43(15):1235-42. doi: 10.1016/j.jpsychires.2009.04.008;Lars-Göran Öst, Ulf Sterner: A specific behavioral method for treatment of blood phobia. Behaviour Research and Therapy Volume 25, Issue 1, 1987, Pages 25–29 doi: 10.1016/0005-7967(87)90111-2;Lars-Göran Öst, Anita Jerremalm, Jan Johansson: Individual response patterns and the effects of different behavioral methods in the treatment of social phobia. Behaviour Research and Therapy. Volume 19, Issue 1, 1981, Pages 1–16 doi: 10.1016/0005-7967(81)90107-8;Ryan C. Shorey and Gregory L. Stuart: Manualized Cognitive-Behavioral Treatment of Social Anxiety Disorder: A Case Study. Clin Case Stud. 2012 Feb 1; 11(1): 35–47. doi: 10.1177/1534650112438462 (not cited).


Spiroplasma citri causes stubborn disease in Citrus spp. and diseases in other plants. Here, we report the nucleotide sequence of the 1,599,709-bp circular chromosome and two plasmids of S. citri strain R8-A2T. This information will facilitate analyses to understand spiroplasmal pathogenicity and evolutionary adaptations to lifestyles in plants and arthropod hosts. Sympt–coplasma –13. Onlyoplasma –, 15, fors coined , was thema citri , 17.Spiroplasma kunkelii CR2-3X (S. citri strain R8-A2T (Morocco-R8-A2 [ATCC 27556T]), which was originally isolated from stubborn diseased citrus [Citrus sinensis (L.) Osbeck var. Washington navel] , CP013198 (plasmid pSCI26), and CP013199 (plasmid pSCI15). The sequence versions described in this paper are CP013197.1, CP013198.1, and CP013199.1, respectively.This genome project has been deposited in GenBank under BioProject ID PRJNA296877, BioSample accession number SAMN04110376, and GenBank accession numbers


Psammomys obesus as an animal model of diet-induced type 2 diabetes when subjected to a hypercaloric regimen.Type 2 diabetic retinopathy is the main cause of acquired blindness in adults. The aim of this work was to examine the retinal function of the sand rat Psammomys obesus by high caloric diet . The visual function of control (n = 7) and diabetic (n = 7) adult rodents were followed up during 28 consecutive weeks with full-field electroretinogram(ERG) recordings evoked to flashes of white light according to the standard protocol of the International Society for Clinical Electrophysiology of Vision protocol (ISCEV).Hyperglycemia was induced in Twenty-eight weeks following the induction of diabetes, results revealed significantly reduced and delayed photopic and scotopic ERG responses in diabetic rats compared to control rats. More specifically, we noted a significant decrease in the amplitude of the dark-adapted 0.01ERG (62%), a- and b-wave amplitudes of the dark-adapted 3.0 ERG  and the four major oscillatory potentials components (OP1-OP4) . In photopic conditions, diabetic rats showed a significant decrease in a- and b-wave , photopic negative response (55.3%), 30 Hz flicker (63.7%), OP1-OP4 and S-cone (34.7%). Significantly delayed implicit times were observed for all ERG components in the diabetic animals. Results obtained are comparable to those characterizing the retinal function of patients affected with advanced stage of diabetic retinopathy.Psammomys obesus is a useful translational model to study the pathophysiology of diabetic retinopathy in order to explore new therapeutic avenues in human patients. Diabetic retinopathy (DR), which can lead to blindness in severe cases, is reported to affect more than 90% of diabetic patients . The patPsammomys obesus (P.obesus) fed with a high caloric diet will spontaneously develop type 2 diabetes, with accompanying retinopathy, thus making them a valid translational model of this retinal disorder . Of interest, in the present study, all P.obesus which developed DR after 28 weeks of high-fat treatment also developed a retinal dysfunction as measured with the ERG.Electrophysiological evaluation after the morphological assessment in diabetic P.obesus  was needinopathy , 32, 33.inopathy  on the msubjects , making P.obesus. These functional changes suggest that photoreceptor function, as well as synaptic transmission from the photoreceptors to bipolar cells, were affected in vivo by the high-fat induced hyperglycemia [P.obesus showed a decreased expression of both PKC α and ζ isoforms that are Ca2+ independent and co-localized in rod bipolar cells[P.obesus retina. Another alteration detected in diabetic retina in our previous study affecting the synaptic terminals by an increase in synaptic proteins such as synaptophysin [P.obesus viewed as an indicator of retinal cell stress [in vitro by Baccouche et al. [P.obesus were present for both scotopic (rod-mediated) and photopic (cone-mediated) conditions, indicating that both retinal systems are affected in our animal model of diabetic retinopathy. Based on ERG abnormalities and histologic findings in advanced human DR, a significant decrease in amplitudes of scotopic a- and b- waves from pre-proliferative DR [P.obesus at 28 weeks after diabetes induction. A calculation of b-/a-wave amplitude ratios in the present study revealed a declined in scotopic condition, suggesting that bipolar cells are more affected than photoreceptors. However, in photopic condition the unchanged ratio showed that the decrease of b-wave amplitude was correlated to the photoreceptoral response.Our results demonstrated that the amplitude of a- and b- waves ERG of diabetic rodents at 28weeks were significantly reduced, and the implicit times were considerably delayed compared to control glycemia , 34. Thelar cells. This detophysin . The uprl stress . These ce et al. . ERG abnative DR  indicateative DR . The darative DR  is reporative DR –41. Thusative DR . Chung eative DR  reportedative DR –46 and iP.obesus may be explained by the loss of amacrine cells numbers at different cell retinal layers including retinal ganglion cells [P.obesus ERG were comparable to what is reported in human patients at the proliferative stage in diabetic retinopathy [P.obesus.Our results also provide evidence of retinal impairments beyond the level of the photoreceptors in rodents with diabetes, given that OPs were shown to signal inner retinal activity, particularly the amacrine cells , 48. Alton cells . These con cells , 49–51, inopathy –54. Thisinopathy , 55–57, P.obesus model mimics several of the DR features observed in human diabetes and should therefore be considered as a valid alternative to test therapeutic pharmacological molecules on type 2 DR functions.Currently available diabetic rodent models can be used to study the initial (acute) or latent phase of diabetic retinopathy and several studies have reported a concurrent change in OPs , 58, 59.P.obesus after 7 months of diabetic induction.The i-wave of the human full-field photopic ERG response is a relatively small positive deflection following the b-wave and is thought to originate in an off-circuitry in the inner retina . AlthougP.obesus were previously reported by our laboratory showing a reduction by 44% of RGCs in diabetic P.obesus retina after 7 months of diabetes progression [Degeneration of the retinal ganglion cells (RGC) and deterioration of the inner nuclear layer in the retinas of diabetic gression . In the gression , 69. In gression , 70, 71.P.obesus was reduced in amplitude and delayed in timing, similar to what was previously reported in human diabetes [P.obesus. Recognition of these defects will enhance our understanding of the pathophysiology of diabetic retinopathy.Our results also showed that the photopic flicker ERG of our diabetic diabetes , 72, 73.diabetes . The timdiabetes  describeP.obesus was significantly reduced in amplitude and delayed in timing. The cone short-wavelength opsin staining was detectably reduced in P.obesus diabetic retinas and this was confirmed by Western blot analysis in our previous study [Finally, as previously shown in diabetic human subjects , 76, theus study .P.obesus and the corresponding changes in human DR and support the notion that it represents a valid translational model to study the retinal pathophysiological processes involved in the onset and progression of type 2 diabetic retinopathy.”In summary, the totally of our findings regarding ERG presented in this report further confirms the similarity between the characteristics of retina changes in diabetic P.obesus. Such studies should include fundus photography, optical coherence tomography and fluorescein angiography in order to clarify to what extent the ERG findings correlate (precede or follow) with morphological changes in the retina.Clearly, more studies are needed to better correlate structural and functional changes in the diabetic retina of The present study clearly demonstrated for the first time that long-lasting and significant alterations in visual function detected by full-field ERG take place after 28 weeks of diet-induced type 2 diabetes in the retina of the sand rat. Thus, the diabetic sand rat appears to be an animal model that mimics several important features of the human form of diabetic retinopathy.P.obesus as a useful translational model to study diet-induced type 2 diabetic retinopathy . We strongly believe that adding this new model to the researchers’ armamentarium will not only be instrumental in increasing our understanding of the pathophysiology of human diabetic retinopathy but also help in the development of new therapeutic strategies.Our results confirm the validity of the S1 Fig2 flash. (B) Mixed response using 3 cd.s/m2 flash. (C) Photopic responses using 3 cd.s/m2 flash. (D) Photopic 30 Hz flicker response. (E) Photopic S-cone response using 0.0045cd.s/m2 blue flash on an orange background.Representative traces indicating: (A) Rod responses using 0.01 cd.s/m(TIF)Click here for additional data file.S2 Fig2 flash. (B) Mixed response using 3 cd.s/m2 flash. (C) Photopic responses using 3 cd.s/m2 flash. (D) Photopic 30 Hz flicker response. (E) Photopic S-cone response using 0.0045cd.s/m2 blue flash on an orange background.Representative traces indicating: (A) Rod responses using 0.01 cd.s/m(TIF)Click here for additional data file.S3 Fig2 flash. (B) Mixed response using 3 cd.s/m2 flash. (C) Photopic responses using 3 cd.s/m2 flash. (D) Photopic 30 Hz flicker response. (E) Photopic S-cone response using 0.0045cd.s/m2 blue flash on an orange background.Representative traces indicating: (A) Rod responses using 0.01 cd.s/m(TIF)Click here for additional data file.S4 Fig2 flash. (B) Mixed response using 3 cd.s/m2 flash. (C) Photopic responses using 3 cd.s/m2 flash. (D) Photopic 30 Hz flicker response. (E) Photopic S-cone response using 0.0045cd.s/m2 blue flash on an orange background.Representative traces indicating: (A) Rod responses using 0.01 cd.s/m(TIF)Click here for additional data file.S5 Fig2 flash. (B) Mixed response using 3 cd.s/m2 flash. (C) Photopic responses using 3 cd.s/m2 flash. (D) Photopic 30 Hz flicker response. (E) Photopic S-cone response using 0.0045cd.s/m2 blue flash on an orange background.Representative traces indicating: (A) Rod responses using 0.01 cd.s/m(TIF)Click here for additional data file.S6 Fig2 flash. (B) Mixed response using 3 cd.s/m2 flash. (C) Photopic responses using 3 cd.s/m2 flash. (D) Photopic 30 Hz flicker response. (E) Photopic S-cone response using 0.0045cd.s/m2 blue flash on an orange background.Representative traces indicating: (A) Rod responses using 0.01 cd.s/m(TIF)Click here for additional data file.S7 Fig2 flash. (B) Mixed response using 3 cd.s/m2 flash. (C) Photopic responses using 3 cd.s/m2 flash. (D) Photopic 30 Hz flicker response. (E) Photopic S-cone response using 0.0045cd.s/m2 blue flash on an orange background.Representative traces indicating: (A) Rod responses using 0.01 cd.s/m(TIF)Click here for additional data file.S8 Fig2 flash. (B) Mixed response using 3 cd.s/m2 flash. (C) Photopic responses using 3 cd.s/m2 flash. (D) Photopic 30 Hz flicker response. (E) Photopic S-cone response using 0.0045cd.s/m2 blue flash on an orange background.Representative traces indicating: (A) Rod responses using 0.01 cd.s/m(TIF)Click here for additional data file.S9 Fig2 flash. (B) Mixed response using 3 cd.s/m2 flash. (C) Photopic responses using 3 cd.s/m2 flash. (D) Photopic 30 Hz flicker response. (E) Photopic S-cone response using 0.0045cd.s/m2 blue flash on an orange background.Representative traces indicating: (A) Rod responses using 0.01 cd.s/m(TIF)Click here for additional data file.S10 Fig2 flash. (B) Mixed response using 3 cd.s/m2 flash. (C) Photopic responses using 3 cd.s/m2 flash. (D) Photopic 30 Hz flicker response. (E) Photopic S-cone response using 0.0045cd.s/m2 blue flash on an orange background.Representative traces indicating: (A) Rod responses using 0.01 cd.s/m(TIF)Click here for additional data file.S11 Fig2 flash. (B) Mixed response using 3 cd.s/m2 flash. (C) Photopic responses using 3 cd.s/m2 flash. (D) Photopic 30 Hz flicker response. (E) Photopic S-cone response using 0.0045cd.s/m2 blue flash on an orange background.Representative traces indicating: (A) Rod responses using 0.01 cd.s/m(TIF)Click here for additional data file.S12 Fig2 flash. (B) Mixed response using 3 cd.s/m2 flash. (C) Photopic responses using 3 cd.s/m2 flash. (D) Photopic 30 Hz flicker response. (E) Photopic S-cone response using 0.0045cd.s/m2 blue flash on an orange background.Representative traces indicating: (A) Rod responses using 0.01 cd.s/m(TIF)Click here for additional data file.


Microbacterium hominis 84-0209T and M. laevaniformans 91-0039 were studied. Genome sizes  were 3,506,522 (70.96%) and 2,999,965 (69.51%), respectively. Annotation revealed: (M. hominis) three rRNA sequences, 45 tRNA genes, and 3,218 coding sequences; (M. laevaniformans) three rRNA sequences, 49 tRNA genes, and 2,874 coding sequences.Draft genomes for  Microbacterium are environmentally derived, Gram stain-positive bacilli which infrequently cause opportunistic infections in humans (T (CDC group A-4) and LCDC 91-0039 (CDC group A-5) were shared by Health Canada’s Laboratory Centre for Disease Control  with European and Japanese colleagues as part of an effort to assign provisionally named bacteria to validly published genera. Many CDC group A-4 and A-5 isolates were assigned to the genus Microbacterium in 1995 after 16S rRNA gene sequencing analysis  as well as M. laevaniformans LCDC 91-0039  (T and LCDC 91-0039.Members of the genus n humans . Some ofn humans . LCDC 84DNA was extracted using the TruseqR DNA HT sample preparation kit. Paired-end whole-genome shotgun libraries were constructed using TruseqR Nano DNA HT library preparation kit and mate-pair libraries for each strain were prepared using the Nextera mate-pair sample preparation kit (Illumina). Sequencing was performed using a MiSeq sequencer (Illumina).M. hominis and M. laevaniformans generated 2,296,026 and 1,583,940 reads; mate-pair libraries gave rise to 2,272,076 reads and 2,768,080 reads, respectively. Overlapping paired-end reads were merged using FLASH (fast length adjustment of short reads)  predicted three rRNA sequences, 45 tRNA genes, and 3,218 coding sequences. Data was highly consistent (>99% symmetric identity [SI]) with an unpublished genome of M. hominis NBRC 15708T (Genbank [GB] accession no. NZ_BCW100000000.1); both genomes were not closely related (63% SI) to GB NZ_JWSZ00000000.1. Annotation of M. laevaniformans using Prokka  and repeat sequences; mate-pair reads were added to contigs using Sspace (v2.0.0) to produce scaffolds . This reM. hominis LCDC 84-0209T and M. laevaniformis LCDC 91-0039 have been deposited at DDBJ/EMBL/GenBank under accession no. LRYC00000000 and LRAD00000000.Draft whole-genome projects for


Escherichia coli (ETEC) is a major cause of diarrhoea in children below 5 years of age in endemic areas, and is a primary cause of diarrhoea in travellers visiting developing countries. Epidemiological analysis of E. coli pathovars is traditionally carried out based on the results of serotyping. However, genomic analysis of a global ETEC collection of 362 isolates taken from patients revealed nine novel O-antigen biosynthesis gene clusters that were previously unrecognized, and have collectively been called unclassified. When put in the context of all isolates sequenced, one of the novel O-genotypes, OgN5, was found to be the second most common ETEC O-genotype causing disease, after O6, in a globally representative ETEC collection. It’s also clear that ETEC OgN5 isolates have spread globally. These novel O-genotypes have now been included in our comprehensive O-genotyping scheme, and can be detected using a PCR-based and an in silico typing method. This will assist in epidemiological studies, as well as in ETEC vaccine development.Enterotoxigenic  CF, colonization factor; ETEC, enterotoxigenic Escherichia coli; LT, heat-labile toxin; O-AGC, O-antigen biosynthesis gene cluster; OgUT, O-genotype untypeable; ST, heat-stable toxin; STEC, Shiga toxin-producing Escherichia coli.Escherichia coli isolates were deposited in GenBank/EMBL/DDBJ under the accession numbers shown in Table S1 .1. Assembled draft genomes for 55 enterotoxigenic wzy genes from positive control strains  were deposited in GenBank/EMBL/DDBJ under the accession numbers LC177546–LC177554 and LC223608–LC223610, respectively.2. Sequences of nine annotated O-antigen biosynthesis gene clusters and three Escherichia coli (ETEC) isolates. The novel O-genotype OgN5 was found to be the second most common ETEC O-genotype globally, with no prior information regarding the contribution to the burden of disease. To gain more information about trends in ETEC OgN epidemiology, further studies of global OgN isolates are needed. The PCR method described in this study and an in silico typing method may help the surveillance and monitoring of the OgN groups.We identified nine novel O-genotypes (OgN) in a global collection of enterotoxigenic Escherichia coli (ETEC) [The first diarrhoeal illness that infants often experience in endemic areas is caused by enterotoxigenic i (ETEC) . In 2010i (ETEC) . The majE. coli isolates, especially pathogenic E. coli, for taxonomical and epidemiological studies. Most of what we know about E. coli prevalence, outbreaks and surveillance is described in terms of the O-serogroup. Recently, sequence analyses show that phenotypic O-serogroup diversification can be correlated with differences in the gene content and genetic diversity of the O-antigen biosynthesis gene cluster (O-AGC) located on the chromosome [wzx (encoding the O-antigen flippase), wzy (encoding the O-antigen polymerase), and the wzm and wzt genes (encoding components of the ABC transporter pathway) located on the O-AGCs are highly variable in sequence, and can be used as gene markers for the identification of O-serogroups via molecular approaches [in silicoblast analysis using a wzx/wzy and wzm/wzt sequence set extracted from O1 to O187 O-AGCs, we subtyped our 362 global ETEC isolates [n=38), O25 (n=24), O27 (n=18), O114 (n=17), O115 and O159 . In addition to the ETEC isolates classified into 48 known O-genotypes, 55 isolates carried wzx/wzy genes that showed <50 % or no sequence identity to the previously defined sequences. These ETEC isolates were categorized as O-genotype untypeable (OgUT), but carried novel O-AGCs.O-serogrouping remains the gold standard for the subtyping of romosome . In partproaches . By applIn this study, we focused on characterizing the OgUT ETEC isolates detected in our previous study . Such ETwzx and wzy sequences were extracted from each O-AGC. The known wzx/wzy sequences from typical E. coli O-serogroups  [Shigella O-serogroups  [E. coli OX serogroups  [E. coli  [wzy genes of OX25 and S. dysenteriae type 6, which are not found in the O-AGCs). A complete set of fliC sequences [ETEC O-AGC sequences were obtained from draft genomes used in a previous study . The wzx groups) , Shigell sonnei) , E. coliwzx and wzy were constructed by using the neighbour-joining algorithm using mega5 software [clustal W program [Phylogenetic trees of software , followi program .wzy sequences. PCR was performed as follows: the 30 µl reaction mixture contained 2 µl genomic DNA, 6 µl 5× Kapa Taq buffer, dNTP mix , MgCl2 , primers  and 0.8 U Kapa Taq DNA polymerase (Kapa Biosystems). The thermocycling conditions were: 25 cycles of 94 °C for 30 s, 58 °C for 30 s and 72 °C for 1 min. The PCR products were visualized following agarose gel (1.5 %) electrophoresis in 0.5x TBE  and staining with ethidium bromide (1 mg/ml). Three strains  were used as positive-control strains for PCR.OgN-specific PCR primers targeting OgN3, OgN5 and OSB16 were designed based on each alignment of wca) (upstream) and the histidine biosynthesis (his) (downstream) extracted from OgUT ETEC genomes contained nine novel O-AGCs, OgN2, OgN3, OgN4, OgN5, OgN13, OgN14, OgN15, OgN16 and OgN17  (wzx and wzy were highly conserved within each O-genotype (99.8–100 % sequence identity). ETEC OgN5 strains were isolated in five countries, Guatemala (n=12), Argentina (n=5), Egypt (n=4), Mexico (n=4) and Indonesia (n=4), between 1989 and 2003. All ETEC OgN5 isolates carried the ST-encoding gene, except for a single isolate (E1542) that carried the LT-encoding gene, and all OgN5 isolates were confirmed negative for all known CFs by dot-blot and PCR-based analyses in our previous study [fliC-based H-typing showed that the OgN5 isolates were classified into eight H-types: H5, H9, H10, H16, H18, H19, H32 and H39 (see Table S1). Phylogenetic analysis showed OgN5 isolates were spread across phylogenetically distinct lineages where most/some isolates grouped based on their H-types . The major groups were OgN5 : H10 and OgN5 : H16  belonging to a phylogenetic lineage L14 [E. coli phylogroup A and a lineage L22 (designed in this study) of phylogroup B, respectively . Additionally, OgN5 : H18 , OgN5 : H9 , OgN5 : H32 , OgN5 : H19 , OgN5 : H34 , OgN5 : H16  and OgN5 : H5  were observed. No significant association between lineages and geographical origins was observed (see Table S1).Comparative analyses revealed that chromosomal O-AGC sequences flanked by gene clusters of the colanic acid biosynthesis  . Among t (OSB16) . A summafliC of H45, and were confirmed positive for STh and two CFs, CFA/I (a fimbria) and CS21 (a type IV pilus) (see Table S1). All OgN3 : H45 isolates were phylogenetically grouped into L6 of phylogroup A, and originated from Central and South America, including Mexico, Guatemala and Argentina . Six of eight OSB16 strains carried the fliC of H32, and were confirmed positive for LT, LT+STh or LT+STp, and negative for all known CFs (see Table S1). All OSB16 : H32 and OSB16 : H2 isolates were phylogenetically grouped into L13 of phylogroup A, and originated from Guatemala and Argentina . Additionally, three OgN13, two OgN15 and single OgN2, OgN4, OgN14, OgN16 and OgN17 strains were observed in our ETEC collection (see Table S1).Six of eight OgN3 strains carried the wzy genes  associated with diarrhoeal patients in Egypt , Boliviawzx/wzy from O-AGCs were highly conserved within each O-genotype, indicating that these O-AGCs have been spread across this species by horizontal gene transfer. Phylogenetic analysis in our previous study [Novel O-genotype ETEC isolates were found in several distinct phylogenetic lineages, and sequences of us study  showed tin silico-based serotyping web tool, SerotypeFinder, of the Center for Genomic Epidemiology (https://cge.cbs.dtu.dk/services/SerotypeFinder) [E. coli O-antigen associated genes  from O1 to O187 and H-antigen associated genes (fliC and its homologues) from H1 to H56 can be used to estimate E. coli O : H serotypes of sequenced isolates. If it is possible to organize and update the database with new wzx and wzy sequences, it becomes possible to meet the requirements for broader O-genotypes, including OgN5, OgN3 and OSB16 in the in silico typing.Recently, we have been able to access whole-genome sequencing data due to the appearance of next-generation sequence technologies. A publicly available eFinder) , which hin silico typing method.In conclusion, by using detailed whole genome sequence-based analyses, it is clear that there is a hidden diversity of ETEC O-genotypes for which there is no prior information regarding their contribution to the burden of disease. It should be noted that even from our global collection, ETEC isolates from Africa are underrepresented. Hence, it is possible and perhaps likely that additional novel ETEC O-types and their associated lineages will continue to be discovered. 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Corynebacterium CDC group F-1 were assembled and studied. Genome sizes ranged between 2.3 and 2.44 Mb, with G+C content between 60.4% and 60.7%.Three draft and one complete genome sequence from strains isolated from urine and consistent with  Corynebacterium based on biochemical results and other phenotypic traits  published an identification scheme for isolates consistent with the genus roup F-1 . Here, fDNA was extracted using the TruSeq DNA high-throughput (HT) sample preparation kit. Paired-end whole-genome shotgun libraries were constructed using TruSeq Nano DNA HT library preparation kit. A mate-pair library for strain NML 98-0116 was prepared using the Nextera mate-sample prep kit (Illumina). Sequencing was performed using a MiSeq sequencer (Illumina), and assembly was performed with SPAdes version 3.1.1) . Contigs.1.1 . Cohttps://www.ncbi.nlm.nih.gov/genome/annotation_prok). Assembled whole genomes demonstrated essentially identical G+C contents, genome sizes, and number of coding regions , with a G+C content of 56.72% (Corynebacterium species (ermX gene (associated with resistance to erythromycin and clindamycin) homologous to that found in Corynebacterium urealyticum, Corynebacterium jeikeium, and Corynebacterium striatum. This was consistent with published antibiograms for these strains  Prokaryotic Genome Annotation Pipeline (PGAP) ( regions . The gen regions . Using t regions . NML 140 strains , consist strains .Corynebacterium CDC group F-1 isolates have been deposited in GenBank under accession numbers shown in Complete or draft genome sequences of four


The publisher apologizes for the error. The correct citation is: Zou W, Yadav S, DeVault L, Jan YN, Sherwood DR (2015) RAB-10-Dependent Membrane Transport Is Required for Dendrite Arborization. PLoS Genet 11(9): e1005484. doi:10.1371/journal.pgen.1005484This article was republished on October 21, 2015, to correct an XML error causing the 4S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.


Plasmodium parasites to bind and invade target cells. Hence, characterising molecules that participate in reticulocyte interaction is key to understanding the molecular basis of Plasmodium vivax invasion. This study focused on predicting functionally restricted regions of the P. vivax GPI-anchored micronemal antigen (PvGAMA) and characterising their reticulocyte binding activity.Adhesin proteins are used by pvgama gene was initially found in P. vivax VCG-I strain schizonts. According to the genetic diversity analysis, PvGAMA displayed a size polymorphism very common for antigenic P. vivax proteins. Two regions along the antigen sequence were highly conserved among species, having a negative natural selection signal. Interestingly, these regions revealed a functional role regarding preferential target cell adhesion.The PvGAMA reticulocyte binding properties for the first time. Conserved functional regions were predicted according to natural selection analysis and their binding ability was confirmed. These findings support the notion that PvGAMA may have an important role in P. vivax merozoite adhesion to its target cells.To our knowledge, this study describes The online version of this article (doi:10.1186/s13071-017-2183-8) contains supplementary material, which is available to authorized users. Plasmodium vivax is a human malaria-causing parasite whose eradication is a priority on the international health agenda C[G/C]C[A/T]AA[C/T][C/G][A/G/C][G/A]AC[G/C/A] repeat which was not present in P. cynomolgi, P. inui, P. fragile, P. knowlesi or P. coatneyi , P > 0.1). However, synonymous divergence was greater than non-synonymous divergence (P < 0.0001) when comparing pvgama sequences to each related species: KN-KSP. vivax/P. cynomolgi = -0.041 (0.006); KN-KSP. vivax/P. inui = -0.062 (0.008); KN-KSP. vivax/P. fragile = -0.030 (0.006); KN-KSP. vivax/P. knowlesi = -0.072 (0.009); KN-KSP. vivax/P. coatneyi = -0.049 (0.007). The evolutionary rate ω (dN/dS and KN/KS) sliding window showed that two highly conserved regions amongst species (codons 80–320 and 514–624) might be under negative selection (ω < 0.5). Furthermore, 308 negatively-selected codons were observed amongst species  whilst 67.5% of them recognised rPvGAMA-Ct (0.47 cut-off point). These data agreed with a study of the profile of the humoral immune response for P. vivax in which rPvGAMA was recognised by 54.5% of the sera used in the array AN[A/G][N/D] was predicted. This RR was common in different ce Pv12 ) or in tce . DN. DNP. vi  or in t regions , 53. Thimsp4  showed higher rosetting activity, unlike the F1 region (aa 22 to 344) (amino fragment) : percentage of sites evolving under positive selection. P-value corrected for multiple tests using the Holm-Bonferroni method. (TIF 470 kb)Lineage-specific positive selection. Branches under positive episodic selection were identified by using the REL-site branch method. Episodic selection acts very quickly and involves a switch from negative to positive natural selection and back to negative and might enable adaptation to a new host. Phylogeny was inferred in MEGA v6 by the maximum likelihood method using the GTR + G evolutionary model. ωAdditional file 3: Figure S3.PvGAMA-Nt and -Ct stained with Coomassie blue or analysed by western blot using anti-polyhistidine antibodies, respectively. c Purifying conserved (CR1 and CR2) and variable (VR1 and VR2) PvGAMA regions. Lanes 2, 4, 6 and 8 show purified recombinant proteins and lanes 3, 5, 7 and 9 show western blot detection. The proteins’ molecular markers are indicated in Lane 1 on all figures. (TIF 5327 kb)Obtaining recombinant proteins. a, b Recombinant GAMA protein expression and purification. Lanes 2–3 show non-induced and induced cell lysate, respectively. Lanes 4–5 show purified rAdditional file 4: Figure S4.Selection strategy for immature and mature erythrocyte populations. The doublets were excluded by plotting FSC-H against FSC-A. Cells were then selected by their granularity, using an SSC-A vs FSC-A cytogram. The CD45 vs CD71 signal was plotted for selecting reticulocyte (CD71 + CD45-) and mature erythrocyte (CD71-CD45-) populations and omitting activated lymphocytes (CD71 + CD45+). The percentage of cells having bound protein was calculated using the PE signal (CD71 + CD45-PE+). A representative histogram from three independent experiments analysing the PE signal for the CR2 binding assay compared to control is also shown. (TIF 10448 kb)


During 2000–2013, among adults aged 50–75 years, the use of colorectal cancer tests or procedures increased for all racial and ethnic groups shown. Non-Hispanic Asian adults had the largest increase; the percentage more than doubled from 20.6% in 2000 to 51.2% in 2013. Although increases were observed among all groups, in 2013 the prevalence of colorectal cancer screening remained higher among non-Hispanic white (60.4%) and non-Hispanic black (58.2%) adults and lower among non-Hispanic Asian (51.2%) and Hispanic (41.5%) adults.Source: Health, United States, 2014 . Available at http://www.cdc.gov/nchs/data/hus/hus14.pdf.Reported by: Hashini Khajuria, MPA, hwq6@cdc.gov, 301-458-4253.


Acute myocarditis (AM) is an inflammatory disease of the heart muscle. Clinical presentation and outcome are variable, ranging from asymptomatic to fulminant myocarditis (FM), presenting with decompensated heart failure or cardiogenic shock needing inotropic or mechanical circulatory support. Cardiac magnetic resonance (CMR) is increasingly employed in the diagnosis and follow-up (f.u.) of AM. We investigated the differences in functional parameters evaluated with CMR between patients (pts) presenting with FM versus non fulminant AM (NFM), at baseline and f.u.We retrospectively analyzed consecutive pts with AM who underwent CMR  within 30 days from clinical presentation. Cine, STIR T2-weighted and late-enhancement images were acquired on matching planes. CMR diagnosis of AM was based on Lake Louise Criteria. Indexed LV end-diastolic (LVEDVi) and end-systolic (LVESVi) volumes, LV ejection fraction (LVEF), indexed LV mass (LVmi), indexed RV end-diastolic (RVEDVi) and end-systolic (RVESVi) volumes and RV ejection fraction (RVEF) were calculated for each patient. F.u. scans were similarly analyzed, if available.2, p=0.028) and LVEF improved from 56% to 66% (p=0.028); in NFM LVEDVi and LVEF were unchanged at f.u. . F.u. LVEF and RVEF did not differ significantly between FM and NFM, 66% (60-69) vs 65% (61-69), p=0.79 and 62% (57-68) vs 63% (59-68),p=0.69 respectively. In both FM and NFM LVmi significantly decreased from baseline . There was a trend towards a more pronounced reduction of LVmi in FM, but the difference fell short of statistical significance .Four pts with FM died and 3 were heart transplanted before performing CMR and thus were excluded from the analysis; none of the pts with NFM died or were transplanted before CMR. In total, 68 pts  were included: 11 (16%) with FM and 57 (84%) with NFM underwent CMR. Baseline scans were obtained earlier in the NFM group, 5 (3-9) vs 12 (7-21) days after presentation, p = 0.0035. Baseline LVEF was significantly lower in FM compared to NFM, 56% (43-65) vs 64% (59-68),p=0.026. RVEF was lower in FM than in NFM pts, 56% (52-58) vs 63% (58-66),p=0.0024. F.u. scans were available in 47 pts  and were obtained after a median of 169 (110-203) days from baseline scan in FM and 148 (93-242) days in NFM (p=0.78). In FM, LVEDVi was increased at f.u. (from 75 to 77 mL/mPts with FM achieved normal LVEF at f.u., despite a lower baseline LVEF, even if a mild LV remodeling was observed at f.u. This might in part be due to a more pronounced decrease in LVmi, likely secondary to more severe myocardial edema in FM, but this observation warrants further investigation and longer f.u. to better understand long term consequences of FM on ventricular remodeling and prognosis.