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- Architecture of Class 1, 2, and 3 Integrons from Gram Negative Bacteria Recovered among Fruits and VegetablesPublication . Jones-Dias, Daniela; Manageiro, Vera; Ferreira, Eugénia; Barreiro, Paula; Vieira, Luís; Moura, Inês B; Caniça, ManuelaThe spread of antibiotic resistant bacteria throughout the food chain constitutes a public health concern. To understand the contribution of fresh produce in shaping antibiotic resistance bacteria and integron prevalence in the food chain, 333 antibiotic resistance Gram negative isolates were collected from organic and conventionally produced fruits (pears, apples, and strawberries) and vegetables (lettuces, tomatoes, and carrots). Although low levels of resistance have been detected, the bacterial genera identified in the assessed fresh produce are often described not only as environmental, but mostly as commensals and opportunistic pathogens. The genomic characterization of integron-harboring isolates revealed a high number of mobile genetic elements and clinically relevant antibiotic resistance genes, of which we highlight the presence of as mcr-1, qnrA1, bla GES-11, mphA, and oqxAB. The study of class 1 (n = 8), class 2 (n = 3) and class 3 (n = 1) integrons, harbored by species such as Morganella morganii, Escherichia coli, Klebsiella pneumoniae, led to the identification of different integron promoters (PcW, PcH1, PcS, and PcWTNG-10) and cassette arrays (containing drfA, aadA, cmlA, estX, sat, and bla GES). In fact, the diverse integron backbones were associated with transposable elements (e.g., Tn402, Tn7, ISCR1, Tn2 (*), IS26, IS1326, and IS3) that conferred greater mobility. This is also the first appearance of In1258, In1259, and In3-13, which should be monitored to prevent their establishment as successfully dispersed mobile resistance integrons. These results underscore the growing concern about the dissemination of acquired resistance genes by mobile elements in the food chain.
- Prevalence of microcephaly in Europe: population based studyPublication . Morris, Joan K.; Rankin, Judith; Garne, Ester; Loane, Maria; Greenlees, Ruth; Addor, Marie-Claude; Arriola, Larraitz; Barisic, Ingeborg; Bergman, Jorieke E.H.; Csaky-Szunyogh, Melinda; Dias, Carlos Matias; Draper, Elizabeth S.; Gatt, Miriam; Khoshnood, Babak; Klungsoyr, Kari; Kurinczuk, Jennifer J.; Lynch, Catherine; McDonnell, Robert; Nelen, Vera; Neville, Amanda J.; O'Mahony, Mary T.; Pierini, Anna; Randrianaivo, Hanitra; Rissmann, Anke; Tucker, David; Verellen-Dumoulin, Christine; de Walle, Hermien E.K.; Wellesley, Diana; Wiesel, Awi; Dolk, HelenObjectives: To provide contemporary estimates of the prevalence of microcephaly in Europe, determine if the diagnosis of microcephaly is consistent across Europe, and evaluate whether changes in prevalence would be detected using the current European surveillance performed by EUROCAT (the European Surveillance of Congenital Anomalies). Design: Questionnaire and population based observational study. Setting: 24 EUROCAT registries covering 570 000 births annually in 15 countries. Participants: Cases of microcephaly not associated with a genetic condition among live births, fetal deaths from 20 weeks’ gestation, and terminations of pregnancy for fetal anomaly at any gestation. Main: outcome measures Prevalence of microcephaly (1 Jan 2003-31 Dec 2012) analysed with random effects Poisson regression models to account for heterogeneity across registries. Results: 16 registries responded to the questionnaire, of which 44% (7/16) used the EUROCAT definition of microcephaly (a reduction in the size of the brain with a skull circumference more than 3 SD below the mean for sex, age, and ethnic origin), 19% (3/16) used a 2 SD cut off, 31% (5/16) were reliant on the criteria used by individual clinicians, and one changed criteria between 2003 and 2012. Prevalence of microcephaly in Europe was 1.53 (95% confidence interval 1.16 to 1.96) per 10 000 births, with registries varying from 0.4 (0.2 to 0.7) to 4.3 (3.6 to 5.0) per 10 000 (χ2=338, df=23, I2=93%). Registries with a 3 SD cut off reported a prevalence of 1.74 per 10 000 (0.86 to 2.93) compared with those with the less stringent 2 SD cut off of 1.21 per 10 000 (0.21 to 2.93). The prevalence of microcephaly would need to increase in one year by over 35% in Europe or by over 300% in a single registry to reach statistical significance (P<0.01). Conclusions: EUROCAT could detect increases in the prevalence of microcephaly from the Zika virus of a similar magnitude to those observed in Brazil. Because of the rarity of microcephaly and discrepant diagnostic criteria, however, the smaller increases expected in Europe would probably not be detected. Clear diagnostic criteria for microcephaly must be adopted across Europe.
- The interplay between mRNA translation and nonsense-mediated decay in transcripts with short open reading framesPublication . Onofre, Cláudia; Menezes, Juliane; Peixeiro, Isabel; Barbosa, Cristina; Romão, LuísaMammalian nonsense-mediated mRNA decay (NMD) is a splicing- and translation-dependent surveillance pathway that recognizes and selectively degrades mRNAs carrying premature termination codons (PTCs). In addition, several studies have also implicated NMD in the regulation of steady-state levels of physiological mRNAs, and examples of natural NMD targets are transcripts containing upstream short open reading frames or long 3’ untranslated regions. The strength of the NMD response appears to reflect multiple determinants on a target mRNA. In general, the location of a PTC greater than 50 nucleotides upstream to the last exon-exon junction constitutes a major determinant of NMD. However, we have reported that human mRNAs with a PTC in close proximity to the translation initiation codon (AUG-proximal PTC), and thus, with a short open reading frame, can substantially escape NMD. Our data support a model in which cytoplasmic poly(A)-binding protein 1 (PABPC1) is brought into close proximity with an AUG-proximal PTC via interactions with the translation initiation complexes. This proximity of PABPC1 to the AUG-proximal PTC allows PABPC1 to interact with eRF3 with a consequent enhancement of the release reaction and repression of the NMD response. Here, we present strong evidence that the eIF3 is involved in delivering eIF4G-associated PABPC1 into the vicinity of the AUG-proximal PTC. In addition, we dissect the biochemical interactions of the eIF3 subunits in bridging PABPC1/eIF4G complex to the 40S ribosomal subunit. Together, our data provide a framework for understanding the mechanistic details of PTC definition and translation initiation.