Predicting microRNA modulation in human prostate cancer using a simple String IDentifier (SID1.0).

To make faster and efficient the identification of mRNA targets common to more than one miRNA, and to identify new miRNAs modulated in specific pathways, a computer program identified as SID1.0 (simple String IDentifier) was developed and successfully applied in the identification of deregulated miRNAs in prostate cancer cells. This computationally inexpensive Fortran program is based on the strategy of exhaustive search and specifically designed to screen shared data (target genes, miRNAs and pathways) available from PicTar and DIANA-MicroT 3.0 databases. As far as we know this is the first software designed to filter data retrieved from available miRNA databases. SID1.0 takes advantage of the standard Fortran intrinsic functions for manipulating text strings and requires ASCII input files. In order to demonstrate SID1.0 applicability, some miRNAs expected from the literature to associate with cancerogenesis (miR-125b, miR-148a and miR-141), were randomly identified as main entries for SID1.0 to explore matching sequences of mRNA targets and also to explore KEGG pathways for the presence of ID codes of targeted genes. Besides genes and pathways already described in the literature, SID1.0 has proven to useful for predicting other genes involved in prostate carcinoma. These latter were used to identify new deregulated miRNAs: miR-141, miR-148a, miR-19a and miR-19b. Prediction data were preliminary confirmed by expression analysis of the identified miRNAs in androgen-dependent (LNCaP) and independent (PC3) prostate carcinoma cell lines and in normal prostatic epithelial cells (PrEC).

Local sea level trends, accelerations and uncertainties over 1993-2019.

Satellite altimetry missions provide a quasi-global synoptic view of sea level variations over more than 25 years and provide regional sea level (SL) indicators such as trends and accelerations. Estimating realistic uncertainties on these quantities is crucial to address current climate science questions. While uncertainty estimates are available for the global mean sea level (GMSL), information is not available at local scales so far. We estimate a local satellite altimetry error budget and use it to derive local error variance-covariance matrices, and estimate confidence intervals on trends and accelerations at the 90% confidence level. Over 1993-2019, we find that the average local sea level trend uncertainty is 0.83 mm.yr-1 with values ranging from 0.78 to 1.22 mm.yr-1. For accelerations, uncertainties range from 0.057 to 0.12 mm.yr-1, with a mean value of 0.062. We also perform a sensitivity study to investigate a range of plausible error budgets. Local error levels, error variance-covariance matrices, SL trends and accelerations, along with corresponding uncertainties are provided.

New relative sea-level (RSL) indications from the Eastern Mediterranean: Middle Bronze Age to the Roman period (~3800-1800 y BP) archaeological constructions at Dor, the Carmel coast, Israel.

This article presents new archaeological observations and multidisciplinary research from Dor, Israel to establish a more reliable relative sea level for the Carmel Coast and Southern Levant between the Middle Bronze Age and the Roman period (ca. 3500-1800 y BP). Our record indicates a period of low relative sea level, around -2.5 m below present, from the Middle Bronze Age to the Hellenistic period (ca. 3500-2200 y BP). This was followed by a rapid rise to present levels, starting in the Hellenistic period and concluding during the Roman period (ca. 2200-1800 y BP). These Roman levels agree with other relative sea-level indications from Israel and other tectonically stable areas in the Mediterranean. Several relative sea-level reconstruction models carried out in the current study provide different predictions due to their parameters and do not model the changes observed from field data which points to a non-isostatic origin for the changes. Long-term low stable Iron Age relative sea level can be seen in Dor, where Iron Age harbor structures remain around the same elevation between ca. 3100-2700 y BP. A similar pattern occurs at Atlit, the Iron Age harbor to the north used continuously from ca. 2900 y BP to the beginning of the Hellenistic period (ca. 2200 y BP). An examination of historical and archaeological sources reveals decline and occasional disappearance of Hellenistic sites along the coast of Israel at ca. 2200 y BP (2nd century BCE), as in the case of Yavneh Yam, Ashdod Yam, Straton's Tower, and tel Taninim. In Akko-Ptolemais, the large harbor installations built in the Hellenistic period were never replaced by a substantial Roman harbor. The conclusions of this research are thus relevant for the sea-level research community and for the historical analyses of the Israeli and South Levantine coastline.

Post-LGM coastline evolution of the NW Sicilian Channel: Comparing high-resolution geophysical data with Glacial Isostatic Adjustment modeling.

Since about 20,000 years ago, the geography of the Earth has been profoundly modified by the gradual sea-level rise caused by the melting of continental ice sheets. Flat areas and regions characterized by very low gradients experienced, more than others, rapid flooding, with the progressive disappearance of vast coastal territories. Here we present a reconstruction of the late Quaternary coastline evolution of the north-western sector of the Sicilian Channel, constrained by high-resolution seismic profiles where the marker of the post-Last Glacial Maximum (LGM) marine transgression has been clearly identified and mapped. The locations of the post-LGM seismic horizon have been compared with predictions of a Glacial Isostatic Adjustment (GIA) model, which accounts for the migration of the shorelines in response to sea-level rise and for Earth's rotational and deformational effects associated with deglaciation. We have verified that most of the points mapped through seismic data interpretation fall along the palaeo-coastline that the GIA model predicts for the 21 kyrs B.P. time frame. However, the model shows a misfit in the marine sector between Mazara del Vallo and Sciacca, where the available data indicate a Quaternary tectonic uplift. The analysis of the seismic profiles provides useful constraints to current GIA models. These add on existing histories of relative sea level in the Mediterranean Sea, allowing to gain new insight into the evolution of the palaeo-geography of the region of study and of the whole Sicilian Channel since the LGM, even in areas where direct geophysical observations are not available yet. In this respect, one of the most attractive implications of the ancient coastline evolution is linked with the underwater archaeology. The sea-level rise heavily impacted the distribution of human settlements, possibly forcing site abandonment and migrations, and this is particularly relevant in the Mediterranean basin, the cradle of the western civilization. The underwater traces left by these ancient populations represent the fundamental proofs to reconstruct the early history of our precursors.

Paleofluvial mega-canyon beneath the central Greenland ice sheet.

Subglacial topography plays an important role in modulating the distribution and flow of basal water. Where topography predates ice sheet inception, it can also reveal insights into former tectonic and geomorphological processes. Although such associations are known in Antarctica, little consideration has been given to them in Greenland, partly because much of the ice sheet bed is thought to be relatively flat and smooth. Here, we present evidence from ice-penetrating radar data for a 750-km-long subglacial canyon in northern Greenland that is likely to have influenced basal water flow from the ice sheet interior to the margin. We suggest that the mega-canyon predates ice sheet inception and will have influenced basal hydrology in Greenland over past glacial cycles.

Putative miRNAs for the diagnosis of dyslexia, dyspraxia, and specific language impairment.

Disorders of human communication abilities can be classified into speech and language disorders. Speech disorders (e.g., dyspraxia) affect the sound generation and sequencing, while language disorders (e.g., dyslexia and specific language impairment, or SLI) are deficits in the encoding and decoding of language according to its rules (reading, spelling, grammar). The diagnosis of such disorders is often complicated, especially when a patient presents more than one disorder at the same time. The present review focuses on these challenges. We have combined data available from the literature with an in silico approach in an attempt to identify putative miRNAs that may have a key role in dyspraxia, dyslexia and SLI. We suggest the use of new miRNAs, which could have an important impact on the three diseases. Further, we relate those miRNAs to the axon guidance pathway and discuss possible interactions and the role of likely deregulated proteins. In addition, we describe potential differences in expressional deregulation and its role in the improvement of diagnosis. We encourage experimental investigations to test the data obtained in silico.

MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling.

In order to identify new markers of vascular cell senescence with potential in vivo implications, primary cultured endothelial cells, including human umbilical vein endothelial cells (HUVECs), human aortic endothelial cells (HAECs), human coronary artery endothelial cells (HCAECs) and ex vivo circulating angiogenic cells (CACs), were analysed for microRNA (miR) expression. Among the 367 profiled miRs in HUVECs, miR-146a, miR-9, miR-204 and miR-367 showed the highest up-regulation in senescent cells. Their predicted target genes belong to nine common pathways, including Toll-like receptor signalling (TLR) that plays a pivotal role in inflammatory response, a key feature of senescence (inflammaging). MiR-146a was the most up-regulated miR in the validation analysis (>10-fold). Mimic and antagomir transfection confirmed TLR's IL-1 receptor-associated kinase (IRAK1) protein modulation in both young and senescent cells. Significant correlations were observed among miR-146a expression and ß-galactosidase expression, telomere length and telomerase activity. MiR-146a hyper-expression was also validated in senescent HAECs (>4-fold) and HCAECs (>30-fold). We recently showed that CACs from patients with chronic heart failure (CHF) presented a distinguishing feature of senescence. Therefore, we also included miR-146a expression determination in CACs from 37 CHF patients and 35 healthy control subjects (CTR) for this study. Interestingly, a 1,000-fold increased expression of miR-146a was observed in CACs of CHF patients compared to CTR, along with decreased expression of IRAK1 protein. Moreover, significant correlations among miR-146a expression, telomere length and telomerase activity were observed. Overall, our findings indicate that miR-146a is a marker of a senescence-associated pro-inflammatory status in vascular remodelling cells.