Cancer-Associated noncoding mutations affect RNA G-quadruplex-mediated regulation of gene expression

© 2017 The Author(s). Cancer is a multifactorial disease driven by a combination of genetic and environmental factors. Many cancer driver mutations have been characterised in protein-coding regions of the genome. However, mutations in noncoding regions associated with cancer have been less investigated. G-quadruplex (G4) nucleic acids are four-stranded secondary structures formed in guanine-rich sequences and prevalent in the regulatory regions. In this study, we used published whole cancer genome sequence data to find mutations in cancer patients that overlap potential RNA G4-forming sequences in 5ⲠUTRs. Using RNAfold, we assessed the effect of these mutations on the thermodynamic stability of predicted RNA G4s in the context of full-length 5ⲠUTRs. Of the 217 identified mutations, we found that 33 are predicted to destabilise and 21 predicted to stabilise potential RNA G4s. We experimentally validated the effect of destabilising mutations in the 5ⲠUTRs of BCL2 and CXCL14 and one stabilising mutation in the 5ⲠUTR of TAOK2. These mutations resulted in an increase or a decrease in translation of these mRNAs, respectively. These findings suggest that mutations that modulate the G4 stability in the noncoding regions could act as cancer driver mutations, which present an opportunity for early cancer diagnosis using individual sequencing information.Link_to_subscribed_fulltex

Nezavičajna i invazivna vrsta Paraleucilla magna Klautau, Monteiro & Borojevic, 2004 (Porifera: Calcarea) uz Alžirsku obalu (jugozapadno Sredozemlje)

The non-indigenous and invasive calcareous sponge Paraleucilla magna Klautau, Monteiro & Borojevic, 2004 has been detected for the first time on the Algerian coast. The species has been recorded at high abundance in Algiers Port (Algiers) and in Pisan Island (Béjaïa) during spring 2018. It was present from 2 m to 20 m of depth at the community of seaweeds with filter feeders established on artificial hard substrates and on rocky boulders. Total of 172 individuals were recorded not exceeding 5 cm in height. Anthropogenic activities such as aquaculture farms or shipping traffic might be important vectors or act as stepping-stones in further expansion of Paraleucilla magna.Additional recording of the species adds to the knowledge of its biogeography distribution, biology and ecology in the Mediterranean and may improve selection of key geographical sites for future monitoring on the species proliferation and expansion.Nezavičajna i invazivna karbonatna spužva Paraleucilla magna Klautau, Monteiro i Borojević, 2004, prvi put je otkrivena na alžirskoj obali. Vrsta je zabilježena u velikom broju u luci Alžir (Alžir) i na otoku Pisan (Béjaïa) tijekom proljeća 2018. godine. Prisutna je na dubini od 2 m do 20 m u zajednici morskih algi s filtarskim hranilicama postavljenim na umjetnim tvrdim podlogama i na velikim stijenama. Ukupno su zabilježene 172 jedinke koje ne prelaze 5 cm visine. Antropogene aktivnosti kao što su farme akvakulture ili pomorski promet mogu biti važni vektori ili djelovati kao potporni korak u daljnjem širenju Paraleucilla magna. Dodatno bilježenje vrste doprinosi pozna-vanju njegove bio-geografske distribucije, biologije i ekologije u Sredozemlju, te može poboljšati odabir ključnih geografskih mjesta za buduće praćenje proliferacije i širenja vrste

BREAD QUALITY SUBSTITUTED BY POTATO STARCH INSTEAD OF WHEAT FLOUR

Wheat bread constitutes the most regularly consumed food in the World, the international market for wheat undergoes strong pressure and prices are unceasingly increasing. The aim of this study is to substitute wheat flour by potato starch in bread preparation. Mixtures flours were characterized for composition, damaged starch, and Alveograph properties. According to the results of alveograph parameters, they decrease with the rate of incorporation of potato starch. This decrease can be corrected by adding vital gluten. The results of physicochemical analysis showed a decrease in protein levels, an increase in moisture content (about 2%) and carbohydrates levels due to the composition of potato starch. However, sensory analysis (p ≤ 0.05) showed that the addition 80% of potato starch leads to bread with better characteristics: taste, colour and odour, based on that, it is highly advisable as an ingredient in the standard preparation of wheat bread

The non-indigenous and invasive species Paraleucilla magna Klautau, Monteiro & Borojevic, 2004 (Porifera: Calcarea) in the Algerian coast (Southwestern of Mediterranean Sea)

The non-indigenous and invasive calcareous sponge Paraleucilla magna Klautau, Monteiro & Borojevic, 2004 has been detected for the first time on the Algerian coast. The species has been recorded at high abundance in Algiers Port (Algiers) and in Pisan Island (Béjaïa) during spring 2018. It was present from 2 m to 20 m of depth at the community of seaweeds with filter feeders established on artificial hard substrates and on rocky boulders. Total of 172 individuals were recorded not exceeding 5 cm in height. Anthropogenic activities such as aquaculture farms or shipping traffic might be important vectors or act as stepping-stones in further expansion of Paraleucilla magna. Additional recording of the species adds to the knowledge of its biogeography distribution, biology and ecology in the Mediterranean and may improve selection of key geographical sites for future monitoring on the species proliferation and expansion

SONDEO ARQUEOLÓGICO HUERTO NUEVO [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte, 201

Epigenetic inactivation of the candidate tumor suppressor USP44 is a frequent and early event in colorectal neoplasia

In mouse models, loss of the candidate tumor suppressor gene Ubiquitin Specific protease 44 (USP44) is associated with aneuploidy and cancer. USP44 is also transcriptionally silenced in human cancers. here we investigated the molecular mechanism of USP44 silencing and whether this correlated with aneuploidy in colorectal adenomas. DNA methylation at the USP44 cpG island (CGI) promoter was measured using combined bisulfite restriction analysis (COBRA) in colorectal cancer (CRC) cell lines (n = 18), and with COBRA and bisulfite sequencing in colorectal adenomas (n = 89) and matched normal colonic mucosa (n = 51). the USP44 CGI was hypermethylated in all CRC cell lines, in most colorectal adenomas (79 of 89, 89%) but rarely in normal mucosa samples (3 of 51, 6%). USP44 expression was also compared between normal mucosa and paired hypermethylated adenomas in six patients using qRT-pCR. hypermethylation of the USP44 CGI in adenomas was associated with a 1.8 to 5.5-fold reduction in expression compared with paired normal mucosa. treatment of CRC cell lines with the DNA hypomethylating agent decitabine resulted in a 14 to 270-fold increase in USP44 expression. Whole genome SNP array data showed that gain or loss of individual chromosomes occurred in adenomas, but hypermethylation did not correlate with more aneuploidy. in summary, our data shows that USP44 is epigenetically inactivated in colorectal adenomas, but this alone is not sufficient to cause aneuploidy in colorectal neoplasia. © 2014 Landes Bioscience.Link_to_subscribed_fulltex

Genome-wide analysis of transcriptional regulators in human HSPCs reveals a densely interconnected network of coding and noncoding genes

© 2013 by The American Society of Hematology. Genome-wide combinatorial binding patterns for key transcription factors (TFs) have not been reported for primary human hematopoietic stem and progenitor cells (HSPCs), and have constrained analysis of the global architecture of molecular circuits controlling these cells. Here we provide high-resolution genome-wide binding maps for a heptad of key TFs (FLI1, ERG, GATA2, RUNX1, SCL, LYL1, and LMO2) in human CD341 HSPCs, together with quantitative RNA and microRNA expression profiles. We catalog binding of TFs at coding genes and microRNA promoters, and report that combinatorial binding of all 7 TFs is favored and associated with differential expression of genes and microRNA in HSPCs. We also uncover a previously unrecognized association between FLI1 and RUNX1 pairing in HSPCs, we establish a correlation between the density of histone modifications that mark active enhancers and the number of overlapping TFs at a peak, we demonstrate bivalent histone marks at promoters of heptad target genes in CD341 cells that are poised for later expression, and we identify complex relationships between specific microRNAs and coding genes regulated by the heptad. Taken together, these data reveal the power of integrating multifactor sequencing of chromatin immunoprecipitates with coding and noncoding gene expression to identify regulatory circuits controlling cell identity.Link_to_subscribed_fulltex

Differential DNA repair underlies mutation hotspots at active promoters in cancer genomes

© 2016 Macmillan Publishers Limited. Promoters are DNA sequences that have an essential role in controlling gene expression. While recent whole cancer genome analyses have identified numerous hotspots of somatic point mutations within promoters, many have not yet been shown to perturb gene expression or drive cancer development. As such, positive selection alone may not adequately explain the frequency of promoter point mutations in cancer genomes. Here we show that increased mutation density at gene promoters can be linked to promoter activity and differential nucleotide excision repair (NER). By analysing 1,161 human cancer genomes across 14 cancer types, we find evidence for increased local density of somatic point mutations within the centres of DNase I-hypersensitive sites (DHSs) in gene promoters. Mutated DHSs were strongly associated with transcription initiation activity, in which active promoters but not enhancers of equal DNase I hypersensitivity were most mutated relative to their flanking regions. Notably, analysis of genome-wide maps of NER shows that NER is impaired within the DHS centre of active gene promoters, while XPC-deficient skin cancers do not show increased promoter mutation density, pinpointing differential NER as the underlying cause of these mutation hotspots. Consistent with this finding, we observe that melanomas with an ultraviolet-induced DNA damage mutation signature show greatest enrichment of promoter mutations, whereas cancers that are not highly dependent on NER, such as colon cancer, show no sign of such enrichment. Taken together, our analysis has uncovered the presence of a previously unknown mechanism linking transcription initiation and NER as a major contributor of somatic point mutation hotspots at active gene promoters in cancer genomes.Link_to_subscribed_fulltex