On the Need for Adoption of the Sports Code of the Republic of Belarus

This article discusses the need for the adoption of the Sports Code. The national legislation in the field of sports is analyzed. Foreign experience and its positive impact on the development of sports are considered. The positive and negative aspects following the adoption of the Sports Code are predicted

The \u3cem\u3elet-7\u3c/em\u3e MicroRNA Family Members \u3cem\u3emir\u3c/em\u3e-48, \u3cem\u3emir\u3c/em\u3e-84, and mir-241 Function Together to Regulate Developmental Timing in \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e

The microRNA let-7 is a critical regulator of developmental timing events at the larval-to-adult transition in C. elegans. Recently, microRNAs with sequence similarity to let-7 have been identified. We find that doubly mutant animals lacking the let-7 family microRNA genes mir-48 and mir-84 exhibit retarded molting behavior and retarded adult gene expression in the hypodermis. Triply mutant animals lacking mir-48, mir-84, and mir-241 exhibit repetition of L2-stage events in addition to retarded adult-stage events. mir-48, mir-84, and mir-241 function together to control the L2-to-L3 transition, likely by base pairing to complementary sites in the hbl-1 3′ UTR and downregulating hbl-1 activity. Genetic analysis indicates that mir-48, mir-84, and mir-241 specify the timing of the L2-to-L3 transition in parallel to the heterochronic genes lin-28 and lin-46. These results indicate that let-7 family microRNAs function in combination to affect both early and late developmental timing decisions

Pseudomonas aeruginosa cleaves the decoding center of Caenorhabditis elegans ribosomes

Pathogens such as Pseudomonas aeruginosa advantageously modify animal host physiology, for example, by inhibiting host protein synthesis. Translational inhibition of insects and mammalian hosts by P. aeruginosa utilizes the well-known exotoxin A effector. However, for the infection of Caenorhabditis elegans by P. aeruginosa, the precise pathways and mechanism(s) of translational inhibition are not well understood. We found that upon exposure to P. aeruginosa PA14, C. elegans undergoes a rapid loss of intact ribosomes accompanied by the accumulation of ribosomes cleaved at helix 69 (H69) of the 26S ribosomal RNA (rRNA), a key part of ribosome decoding center. H69 cleavage is elicited by certain virulent P. aeruginosa isolates in a quorum sensing (QS)-dependent manner and independently of exotoxin A-mediated translational repression. H69 cleavage is antagonized by the 3 major host defense pathways defined by the pmk-1, fshr-1, and zip-2 genes. The level of H69 cleavage increases with the bacterial exposure time, and it is predominantly localized in the worm\u27s intestinal tissue. Genetic and genomic analysis suggests that H69 cleavage leads to the activation of the worm\u27s zip-2-mediated defense response pathway, consistent with translational inhibition. Taken together, our observations suggest that P. aeruginosa deploys a virulence mechanism to induce ribosome degradation and H69 cleavage of host ribosomes. In this manner, P. aeruginosa would impair host translation and block antibacterial responses

On the Need for Adoption of the Sports Code of the Republic of Belarus

This article discusses the need for the adoption of the Sports Code. The national legislation in the field of sports is analyzed. Foreign experience and its positive impact on the development of sports are considered. The positive and negative aspects following the adoption of the Sports Code are predicted

Most \u3cem\u3eCaenorhabditis elegans\u3c/em\u3e MicroRNAs are Individually Not Essential for Development or Viability

MicroRNAs (miRNAs), a large class of short noncoding RNAs found in many plants and animals, often act to post-transcriptionally inhibit gene expression. We report the generation of deletion mutations in 87 miRNA genes in Caenorhabditis elegans, expanding the number of mutated miRNA genes to 95, or 83% of known C. elegans miRNAs. We find that the majority of miRNAs are not essential for the viability or development of C. elegans, and mutations in most miRNA genes do not result in grossly abnormal phenotypes. These observations are consistent with the hypothesis that there is significant functional redundancy among miRNAs or among gene pathways regulated by miRNAs. This study represents the first comprehensive genetic analysis of miRNA function in any organism and provides a unique, permanent resource for the systematic study of miRNAs

How to minimise the effect of tumour cell content in detection of aberrant genetic markers in neuroblastoma

Background:Clinical heterogeneity reflects the complexity of genetic events associated with neuroblastoma (NB). To identify the status of all described genetic loci with possible prognostic interest, high-throughput approaches have been used, but only with tumour cell content >60%. In some tumours, necrotic, haemorrhagic and/or calcification areas influence the low amount of neuroblasts. We evaluated the effect of tumour cell content in the detection of relevant aberrant genetic markers (AGM) diagnosed by fluorescence in situ hybridisation (FISH) on tissue microarrays (TMA) in NB.Methods:Two hundred and thirty-three MYCN non-amplified primary NB included in 12 TMAs were analysed.Results:Presence of AGM reduced event-free survival (EFS) (P=0.004) as well as overall survival (OS) (P=0.004) of patients in the whole cohort. There were no differences in prognostic impact of presence of AGM according to tumour cell content.Conclusion:We propose the use of FISH to diagnose AGM of all NB samples having the above-mentioned areas to determine patient risk

Viral Fitness Correlates with the Magnitude and Direction o the Perturbation Induced in the Host's Transcriptome: The Tobacco Etch Potyvirus-Tobacco Case Study

[EN] Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference one, is a complex property that captures, in a single figure, differences in performance at every stage of viral infection. To what extent does viral fitness result from specific molecular interactions with host factors and regulatory networks during infection? Can we identify host genes in functional classes whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus that differ in fitness. We found that the larger the fitness differences among genotypes, the more dissimilar the transcriptomic profiles are. Consistently, two different mutations, one in the viral RNA polymerase and another in the viral suppressor of RNA silencing, resulted in significantly similar gene expression profiles. Moreover, we identified host genes whose expression showed a significant correlation, positive or negative, with the virus' fitness. Differentially expressed genes which were positively correlated with viral fitness activate hormone- and RNA silencing-mediated pathways of plant defense. In contrast, those that were negatively correlated with fitness affect metabolism, reducing growth, and development. Overall, these results reveal the high information content of viral fitness and suggest its potential use to predict differences in genomic profiles of infected hosts.We thank Francisca de la Iglesia and Paula Agudo for excellent technical assistance, the EvolSysVir lab members for help, comments and discussions, Rachel Whitaker for English proofreading, and Lorena Latorre (IBMCP Genomics Service) and Javier Forment (IBMCP Bioinformatics Service) for their assistance. This research was supported by grants from Spain's Agencia Estatal de Investigacion-FEDER (BFU2012-30805 and BFU2015-65037-P to S.F.E. and BFU2015-66894-P to G.R.) and Generalitat Valenciana (PROMETEOII/2014/021).Cervera-Benet, H.; Ambros Palaguerri, S.; Bernet, GP.; Rodrigo Tarrega, G.; Elena Fito, SF. (2018). Viral Fitness Correlates with the Magnitude and Direction o the Perturbation Induced in the Host's Transcriptome: The Tobacco Etch Potyvirus-Tobacco Case Study. 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MicroRNA enrichment among short ‘ultraconserved’ sequences in insects

MicroRNAs are short (∼22 nt) regulatory RNA molecules that play key roles in metazoan development and have been implicated in human disease. First discovered in Caenorhabditis elegans, over 2500 microRNAs have been isolated in metazoans and plants; it has been estimated that there may be more than a thousand microRNA genes in the human genome alone. Motivated by the experimental observation of strong conservation of the microRNA let-7 among nearly all metazoans, we developed a novel methodology to characterize the class of such strongly conserved sequences: we identified a non-redundant set of all sequences 20 to 29 bases in length that are shared among three insects: fly, bee and mosquito. Among the few hundred sequences greater than 20 bases in length are close to 40% of the 78 confirmed fly microRNAs, along with other non-coding RNAs and coding sequence

Molecular and biological characterization of an isolate of Tomato mottle mosaic virus (ToMMV) infecting tomato and other experimental hosts in eastern Spain

[EN] Tomato is known to be a natural and experimental reservoir host for many plant viruses. In the last few years a new tobamovirus species, Tomato mottle mosaic virus (ToMMV), has been described infecting tomato and pepper plants in several countries worldwide. Upon observation of symptoms in tomato plants growing in a greenhouse in Valencia, Spain, we aimed to ascertain the etiology of the disease. Using standard molecular techniques, we first detected a positive sense single-stranded RNA virus as the probable causal agent. Next, we amplified and sequenced its full-length genomic RNA which identified the virus as a new ToMMV isolate. Through extensive assays on distinct plant species, we investigated the host range of the Spanish ToMMV isolate. Several plant species were locally and/or systemically infected by the virus, some of which had not been previously reported as ToMMV hosts despite they are commonly used in research greenhouses. Finally, two reliable molecular diagnostic techniques were developed and used to assess the presence of ToMMV. This is the first observation of ToMMV in tomato plants in Europe. We discuss the possibility that, given the high sequence homology between ToMMV and Tomato mosaic virus, the former may have been mistakenly diagnosed as the latter by serological methods.This work was supported by grants BFU2015-70261-P and BFU2015-65037-P (to C.H. and S.F.E., respectively) from Spain Ministry of Economy, Industry and Competitiveness/FEDER.Ambros Palaguerri, S.; Martinez, F.; Ivars, P.; Hernandez Fort, C.; De La Iglesia Jordán, F.; Elena Fito, SF. (2017). Molecular and biological characterization of an isolate of Tomato mottle mosaic virus (ToMMV) infecting tomato and other experimental hosts in eastern Spain. European Journal of Plant Pathology. 149(2):261-268. https://doi.org/10.1007/s10658-017-1180-2S2612681492Fillmer, K., Adkins, S., Pongam, P., & D’Ella, T. (2015). Complete genome sequence of a Tomato mottle mosaic virus isolated from the United States. Genome Announcements, 3(2), e00167–e00115.Hadas, R., Pearlsman, M., Gefen, T., Lachman, O., Hadar, E., Sharabany, G., et al. (2004). Indexing system for Tomato mosaic virus (ToMV) in commercial tomato seed lots. Phytoparasitica, 32(4), 421–424.Lewandowski, D. J., & Dawson, W. O. (1998). Tobamoviruses. In A. Granoff & R. G. Webster (Eds.), Encyclopedia of virology (Vol. 3, 2nd ed., pp. 1780–1783). New York: Academic Press Inc..Li, R., Gao, S., Fel, Z., & Ling, K. (2013). Complete genome sequence of a new Tobamovirus naturally infecting tomatoes in Mexico. Genome Announcements, 1(5), e00794–e00713.Li, Y. Y., Wang, C. L., Xiang, D., Li, R. H., Liu, Y., & Li, F. (2014). First report of Tomato mottle mosaic virus infection of pepper in China. Plant Disease, 98(10), 1447.Martin, D. P., Murrell, B., Golden, M., Khoosal, A., Muhire, B. (2015). RDP4: detection and analysis of recombination patterns in virus genomes. Virus Evolution, 1(1), vev003.Moreira, S. R., Eiras, M., Chaves, A. L. R., Galleti, S. R., & Colariccio, A. (2003). Characterição de uma nova estirpe do Tomato mosaic virus isolada de tomateiro no estado de São Paulo. Fitopatologia Brasileira, 28(6), 602–607.Padmanabhan, C., Zheng, Y., Li, R., Martin, G. B., Fei, Z., & Ling, K. S. (2015). Complete genome sequence of a tomato-infecting Tomato mottle mosaic virus in New York. Genome Announcements, 3(6), e01523–e01515.Pirovano, W., Boetzer, M., Miozzi, L., & Pantaleo, V. (2015). Bioinformatics approaches for viral metagenomics in plants using short RNAs: Model case of study and application to a Cicer arietinum population. Frontiers in Microbiology, 5, 790.Ruiz-Ruiz, S., Moreno, P., Guerri, J., & Ambrós, S. (2006). The complete nucleotide sequence of a severe stem pitting isolate of Citrus tristeza virus from Spain: Comparison with isolates from different origins. Archives of Virology, 151(2), 387398.Salem, N., Mansour, A., Ciuffo, M., Falk, B. W., & Turina, M. (2016). A new tobamovirus infecting tomato crops in Jordan. Archives of Virology, 161(2), 503–506.Soler, S., Prohens, J., López, C., Aramburu, J., Galipienso, L., & Nuez, F. (2010). Viruses infecting tomato in València, Spain: Occurrence, distribution and effect of seed origin. Journal of Phytopathology, 158(11–12), 797–805.Tamura, L., Stecher, G., Peterson, D., Filipski, A., & Kumar, S. (2013). MEGA6: Molecular evolutionary genetics analysis version 6.0. Molecular Biology and Evolution, 30(12), 2725–2729.Turina, M., Geraats, B. P. J., & Ciuffo, M. (2016). First report of Tomato mottle mosaic virus in tomato crops in Israel. New Disease Reports, 33, 1.Webster, C. G., Rosskopf, E. N., Lucas, L., Mellinger, H. C., & Adkins, S. (2014). First report of Tomato mottle mosaic virus infecting tomato in the United States. Plant Health Progress. doi: 10.1094/PHP-BR-14-0023

Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project

Background: In the INRG dataset, the hypothesis that any segmental chromosomal alteration might be of prognostic impact in neuroblastoma without MYCN amplification (MNA) was tested. Methods: The presence of any segmental chromosomal alteration (chromosome 1p deletion, 11q deletion and/or chromosome 17q gain) defined a segmental genomic profile. Only tumours with a confirmed unaltered status for all three chromosome arms were considered as having no segmental chromosomal alterations. Results: Among the 8800 patients in the INRG database, a genomic type could be attributed for 505 patients without MNA: 397 cases had a segmental genomic type, whereas 108 cases had an absence of any segmental alteration. A segmental genomic type was more frequent in patients >18 months and in stage 4 disease (P<0.0001). In univariate analysis, 11q deletion, 17q gain and a segmental genomic type were associated with a poorer event-free survival (EFS) (P<0.0001, P=0.0002 and P<0.0001, respectively). In multivariate analysis modelling EFS, the parameters age, stage and a segmental genomic type were retained in the model, whereas the individual genetic markers were not (P<0.0001 and RR=2.56; P=0.0002 and RR=1.8; P=0.01 and RR=1.7, respectively). Conclusion: A segmental genomic profile, rather than the single genetic markers, adds prognostic information to the clinical markers age and stage in neuroblastoma patients without MNA, underlining the importance of pangenomic studies