Finite mixture clustering of human tissues with different levels of IGF-1 splice variants mRNA transcripts

BACKGROUND: This study addresses a recurrent biological problem, that is to define a formal clustering structure for a set of tissues on the basis of the relative abundance of multiple alternatively spliced isoforms mRNAs generated by the same gene. To this aim, we have used a model-based clustering approach, based on a finite mixture of multivariate Gaussian densities. However, given we had more technical replicates from the same tissue for each quantitative measurement, we also employed a finite mixture of linear mixed models, with tissue-specific random effects. RESULTS: A panel of human tissues was analysed through quantitative real-time PCR methods, to quantify the relative amount of mRNA encoding different IGF-1 alternative splicing variants. After an appropriate, preliminary, equalization of the quantitative data, we provided an estimate of the distribution of the observed concentrations for the different IGF-1 mRNA splice variants in the cohort of tissues by employing suitable kernel density estimators. We observed that the analysed IGF-1 mRNA splice variants were characterized by multimodal distributions, which could be interpreted as describing the presence of several sub-population, i.e. potential tissue clusters. In this context, a formal clustering approach based on a finite mixture model (FMM) with Gaussian components is proposed. Due to the presence of potential dependence between the technical replicates (originated by repeated quantitative measurements of the same mRNA splice isoform in the same tissue) we have also employed the finite mixture of linear mixed models (FMLMM), which allowed to take into account this kind of within-tissue dependence. CONCLUSIONS: The FMM and the FMLMM provided a convenient yet formal setting for a model-based clustering of the human tissues in sub-populations, characterized by homogeneous values of concentrations of the mRNAs for one or multiple IGF-1 alternative splicing isoforms. The proposed approaches can be applied to any cohort of tissues expressing several alternatively spliced mRNAs generated by the same gene, and can overcome the limitations of clustering methods based on simple comparisons between splice isoform expression levels

IGFBP-3 inhibits Wnt signaling in metastatic melanoma cells.

In previous works, we have shown that insulin-like growth factor-binding protein-3 (IGFBP-3), a tissue and circulating protein able to bind to IGFs, decreases drastically in the blood serum of patients with diffuse metastatic melanoma. In agreement with the clinical data, recombinant IGFBP-3 was found to inhibit the motility and invasiveness of cultured metastatic melanoma cells and to prevent growth of grafted melanomas in mice. The present work was aimed at identifying the signal transduction pathways underlying the anti-tumoral effects of IGFBP-3. We show that the anti-tumoral effect of IGFBP-3 is due to inhibition of the Wnt pathway and depends upon the presence of CD44, a receptor protein known to modulate Wnt signaling. Once it has entered the cell, IGFBP-3 binds the Wnt signalosome interacting specifically with its component GSK-3β. As a consequence, the β-catenin destruction complex dissociates from the LRP6 Wnt receptor and GSK-3β is activated through dephosphorylation, becoming free to target cytoplasmic β-catenin which is degraded by the proteasomal pathway. Altogether, the results suggest that IGFBP-3 is a novel and effective inhibitor of Wnt signaling. As IGFBP-3 is a physiological protein which has no detectable toxic effects either on cultured cells or live mice, it might qualify as an interesting new therapeutic agent in melanoma, and potentially many other cancers with a hyperactive Wnt signaling

THE FUTURE OF WILDFLOWER RESEARCH AND DEVELOPMENT IN SOUTH AFRICA - THE LACHENALIA CASE STUDY

This paper reports the socio-economic impact of the lachenalia research program of the ARCRoodeplaat Vegetable and Ornamental Plant Institute (ARC-Roodeplaat) over the period 1965-2010. Data were collected from researchers, the local propagator and the market agent in Holland, using guidelines and questionnaires. A financial and economic analysis were conducted. The results of both were negative, unless increased productivity, early entry into all potential markets and a decreased research gestation period were assumed. Additional impacts were qualitatively assessed. The program contributed to employment creation, the preservation of biodiversity, capacity building and beneficial institutional linkages. The management information generated by the study was used in planning and priority setting at the institute.Crop Production/Industries, Research and Development/Tech Change/Emerging Technologies,

1976 Base Data for the Dairy Market Policy Simulator

A.E. Res. 80-2

The impact of bilingualism on executive functions in children and adolescents: a systematic review based on the PRISMA method

Approximately half of the world's population is bilingual or multilingual. The bilingual advantage theory claims that the constant need to control both known languages, that are always active in the brain, to use the one suitable for each specific context improves cognitive functions and specifically executive functions. However, some authors do not agree on the bilingual effect, given the controversial results of studies on this topic. This systematic review aims to summarize the results of studies on the relationship between bilingualism and executive functions. The review was conducted according to PRISMA-statement through searches in the scientific database PsychINFO, PsycARTICLES, MEDLINE, and PUBMED. Studies included in this review had at least one bilingual and monolingual group, participants aged between 5 and 17 years, and at least one executive function measure. Studies on second language learners, multilingual people, and the clinical population were excluded. Fifty-three studies were included in the systematic review. Evidence supporting the bilingual effect seems to appear when assessing inhibition and cognitive flexibility, but to disappear when working memory is considered. The inconsistent results of the studies do not allow drawing definite conclusions on the bilingual effect. Further studies are needed; they should consider the role of some modulators (e.g., language history and context, methodological differences) on the observed results

Bleeding jejunal varices and portal thrombosis in a splenectomized patient with hereditary spherocytosis

Bleeding from varices located in the small bowel is a very uncommon finding; nonetheless, such events accompany with a high mortality rate (1– 4). Moreover, early diagnosis of jejunal or ileal varices cannot usually be accomplished with standard diagnostic tools (ie, esophagogastroduodenoscopy, colonoscopy). Most reports in the literature relate to subjects with liver cirrhosis, often with hepatocarcinoma; in unusual anatomical situations, varices may develop beyond the ligament of Treitz in adjunct to the far more common location in the esophageal and gastric wall. Thrombosis of the portal vein is a common feature in such conditions. Portal thrombosis has also been described in association with overt or latent myeloproliferative diseases (5); its occurrence in nonneoplastic hematological conditions in subjects with normal liver function is quite uncommon. This report describes the observation of jejunal varices, with repeated episodes of “melena of unknown origin,” some of which quite severe, as their clinical presentation in a patient with portal thrombosis and with otherwise absolutely normal liver function, who had undergone splenectomy for hereditary spherocytosis in early adolescence

One world, one health, one virology of the mysterious labyrinth of Coronaviruses: the canine coronavirus affair

The described pictures underline the ability of CoVs of driving genetic evolution, to undergoes recombination, and to easy cross interspecies barriers. This potential high genetic recombination ability ensures the proliferation of new strains that may have selective advantages over parental genomes.9 In this aspect, the newly identified CCoV-Hupn-2018 should lead researchers to pay a special attention to the mechanisms of recombination among CoVs, in addition to the onset of variants as a result of mutations. Continuous monitoring of these viruses are required because (without saying as Cassandra…!!!) recombination observed in CCoVs may represent a dramatic warning for SARS-CoV-2