Familial adenomatous patients with desmoid tumours show increased expression of miR-34a in serum and high levels in tumours

Familial adenomatous polyposis (FAP) is rare affecting 1 in 10,000 people and a subset (10%) are at risk of myofibroblastic desmoid tumours (DTs) after colectomy to prevent cancer. DTs are a major cause of morbidity and mortality. The absence of markers to monitor progression and a lack of treatment options are significant limitations to clinical management. We investigated microRNAs (miRNA) levels in DTs and serum using expression array analysis on two independent cohorts of FAP patients (total, n=24). Each comprised equal numbers of patients who had formed DTs (cases) and those who had not (controls). All controls had absence of DTs confirmed by clinical and radiological assessment over at least three years post- colectomy. Technical qPCR validation was performed using an expanded cohort (29 FAP patients; 16 cases and 13 controls). The most significant elevated serum miRNA marker of DTs was miR-34a-5p and in-situ hybridisation (ISH) showed most DTs analysed (5/6) expressed miRNA-34a-5p. Exome sequencing of tumour and matched germline DNA did not detect mutations within the miR-34a-5p transcript sites or 3'-UTR of target genes that would alter functional miRNA activity. In conclusion, miR-34a-5p is a potential circulatory marker and therapy target. A large prospective world-wide multi-centre study is now warranted

ER stress protein AGR2 precedes and is involved in the regulation of pancreatic cancer initiation

The work was supported by a grant A12008 from CR-UK (L. Dumartin, N.R. Lemoine and T. Crnogorac-Jurcevic)

Palaeoclimatic events, dispersal and migratory losses along the Afro-European axis as drivers of biogeographic distribution in Sylvia warblers

<p>Abstract</p> <p>Background</p> <p>The Old World warbler genus <it>Sylvia </it>has been used extensively as a model system in a variety of ecological, genetic, and morphological studies. The genus is comprised of about 25 species, and 70% of these species have distributions at or near the Mediterranean Sea. This distribution pattern suggests a possible role for the Messinian Salinity Crisis (from 5.96-5.33 Ma) as a driving force in lineage diversification. Other species distributions suggest that Late Miocene to Pliocene Afro-tropical forest dynamics have also been important in the evolution of <it>Sylvia </it>lineages. Using a molecular phylogenetic hypothesis and other methods, we seek to develop a biogeographic hypothesis for <it>Sylvia </it>and to explicitly assess the roles of these climate-driven events.</p> <p>Results</p> <p>We present the first strongly supported molecular phylogeny for <it>Sylvia</it>. With one exception, species fall into one of three strongly supported clades: one small clade of species distributed mainly in Africa and Europe, one large clade of species distributed mainly in Africa and Asia, and another large clade with primarily a circum-Mediterranean distribution. Asia is reconstructed as the ancestral area for <it>Sylvia</it>. Long-distance migration is reconstructed as the ancestral character state for the genus, and sedentary behavior subsequently evolved seven times.</p> <p>Conclusion</p> <p>Molecular clock calibration suggests that <it>Sylvia </it>arose in the early Miocene and diverged into three main clades by 12.6 Ma. Divergence estimates indicate that the Messinian Salinity Crisis had a minor impact on <it>Sylvia</it>. Instead, over-water dispersals, repeated loss of long-distance migration, and palaeo-climatic events in Africa played primary roles in <it>Sylvia </it>divergence and distribution.</p

Climatic and topographic changes since the Miocene influenced the diversification and biogeography of the tent tortoise (Psammobates tentorius) species complex in Southern Africa

Background: Climatic and topographic changes function as key drivers in shaping genetic structure and cladogenic radiation in many organisms. Southern Africa has an exceptionally diverse tortoise fauna, harbouring one-third of the world’s tortoise genera. The distribution of Psammobates tentorius (Kuhl, 1820) covers two of the 25 biodiversity hotspots in the world, the Succulent Karoo and Cape Floristic Region. The highly diverged P. tentorius represents an excellent model species for exploring biogeographic and radiation patterns of reptiles in Southern Africa. Results: We investigated genetic structure and radiation patterns against temporal and spatial dimensions since the Miocene in the Psammobates tentorius species complex, using multiple types of DNA markers and niche modelling analyses. Cladogenesis in P. tentorius started in the late Miocene (11.63–5.33 Ma) when populations dispersed from north to south to form two geographically isolated groups. The northern group diverged into a clade north of the Orange River (OR), followed by the splitting of the group south of the OR into a western and an interior clade. The latter divergence corresponded to the intensifcation of the cold Benguela current, which caused western aridifcation and rainfall seasonality. In the south, tectonic uplift and subsequent exhumation, together with climatic fuctuations seemed responsible for radiations among the four southern clades since the late Miocene. We found that each clade occurred in a habitat shaped by diferent climatic parameters, and that the niches difered substantially among the clades of the northern group but were similar among clades of the southern group. Conclusion: Climatic shifts, and biome and geographic changes were possibly the three major driving forces shaping cladogenesis and genetic structure in Southern African tortoise species. Our results revealed that the cladogenesis of the P. tentorius species complex was probably shaped by environmental cooling, biome shifts and topographic uplift in Southern Africa since the late Miocene. The Last Glacial Maximum (LGM) may have impacted the distribution of P. tentorius substantially. We found the taxonomic diversify of the P. tentorius species complex to be highest in the Greater Cape Floristic Region. All seven clades discovered warrant conservation attention, particularly Ptt-B–Ptr, Ptt-A and Pv-

Introducing global peat-specific temperature and pH calibrations based on brGDGT bacterial lipids

Glycerol dialkyl glycerol tetraethers (GDGTs) are membrane-spanning lipids from Bacteria and Archaea that are ubiquitous in a range of natural archives and especially abundant in peat. Previous work demonstrated that the distribution of bacterial branched GDGTs (brGDGTs) in mineral soils is correlated to environmental factors such as mean annual air temperature (MAAT) and soil pH. However, the influence of these parameters on brGDGT distributions in peat is largely unknown. Here we investigate the distribution of brGDGTs in 470 samples from 96 peatlands around the world with a broad mean annual air temperature (-8 to 27 degrees C) and pH (3-8) range and present the first peat-specific brGDGT-based temperature and pH calibrations. Our results demonstrate that the degree of cyclisation of brGDGTs in peat is positively correlated with pH, pH = 2.49 x CBTpeat + 8.07 (n = 51, R-2 = 0.58, RMSE = 0.8) and the degree of methylation of brGDGTs is positively correlated with MAAT, MAAT(peat) (degrees C) = 52.18 x MBT'(5me) - 23.05 (n = 96, R-2 = 0.76, RMSE = 4.7 degrees C). These peat-specific calibrations are distinct from the available mineral soil calibrations. In light of the error in the temperature calibration (similar to 4.7 degrees C), we urge caution in any application to reconstruct late Holocene climate variability, where the climatic signals are relatively small, and the duration of excursions could be brief. Instead, these proxies are well-suited to reconstruct large amplitude, longer-term shifts in climate such as deglacial transitions. Indeed, when applied to a peat deposit spanning the late glacial period (similar to 15.2 kyr), we demonstrate that MAAT(peat) yields absolute temperatures and relative temperature changes that are consistent with those from other proxies. In addition, the application of MAAT(peat) to fossil peat (i.e. lignites) has the potential to reconstruct terrestrial climate during the Cenozoic. We conclude that there is clear potential to use brGDGTs in peats and lignites to reconstruct past terrestrial climate. (C) 2017 The Authors. Published by Elsevier Ltd

Sediment source fingerprinting: benchmarking recent outputs, remaining challenges and emerging themes

Abstract: Purpose: This review of sediment source fingerprinting assesses the current state-of-the-art, remaining challenges and emerging themes. It combines inputs from international scientists either with track records in the approach or with expertise relevant to progressing the science. Methods: Web of Science and Google Scholar were used to review published papers spanning the period 2013–2019, inclusive, to confirm publication trends in quantities of papers by study area country and the types of tracers used. The most recent (2018–2019, inclusive) papers were also benchmarked using a methodological decision-tree published in 2017. Scope: Areas requiring further research and international consensus on methodological detail are reviewed, and these comprise spatial variability in tracers and corresponding sampling implications for end-members, temporal variability in tracers and sampling implications for end-members and target sediment, tracer conservation and knowledge-based pre-selection, the physico-chemical basis for source discrimination and dissemination of fingerprinting results to stakeholders. Emerging themes are also discussed: novel tracers, concentration-dependence for biomarkers, combining sediment fingerprinting and age-dating, applications to sediment-bound pollutants, incorporation of supportive spatial information to augment discrimination and modelling, aeolian sediment source fingerprinting, integration with process-based models and development of open-access software tools for data processing. Conclusions: The popularity of sediment source fingerprinting continues on an upward trend globally, but with this growth comes issues surrounding lack of standardisation and procedural diversity. Nonetheless, the last 2 years have also evidenced growing uptake of critical requirements for robust applications and this review is intended to signpost investigators, both old and new, towards these benchmarks and remaining research challenges for, and emerging options for different applications of, the fingerprinting approach

Photosynthetic pathway of grass fossils from the upper Miocene Dove Spring Formation, Mojave Desert, California

The spread of grasslands in the Miocene and of C4 grasses in the late Miocene-Pliocene represents a major development in terrestrial plant evolution that affected the climate system and faunal evolution. The macrofossil record of grasses is sparse, likely due to the limited preservation potential of grasses. Diagnosis of the C3 or C4 photosynthetic pathway depends on preservation of both cellular structures and organic carbon for isotope analysis. Here we analyze the anatomical and isotopic composition of newly-collected grass fossils from the Dove Spring Formation, Red Rock Canyon State Park, California, USA, located in the El Paso Basin on the western side of the Basin and Range Province, a site previously identified as one of the earliest known C4 grass fossil bearing localities. We analyzed the anatomical and geochemical characteristics of these new grass fossils dated to 12.01–12.15 Ma. The fossils analyzed in this study include grass shoots and in cross-section display anatomy indicative of the C3 photosynthetic pathway. We isolated organic carbon from the stem fossils and determined the carbon isotopic composition to be − 24.8 ± 0.5‰. Together, the anatomical and geochemical analyses confirm that these plants used the C3 photosynthetic pathway. Our findings are consistent with dietary evidence based on tooth enamel from grazing mammals of available C3 resources in the same sections. These newly reported Miocene-age C3 grass fossils contribute to a sparse macrofossil record of grass evolution. Overall, paleoecological reconstructions at this site indicate more humid conditions during the Miocene compared to the modern Mojave Desert with C3 grasses and diverse grazing mammals

Production of leaf wax n-alkanes across a tropical forest elevation transect

Waxy compounds form the boundary layer of the living leaf and contribute biomarkers to soils, and lake and marine sediments. Cataloging the variation in leaf wax traits between species and across environmental gradients may contribute to the understanding of plant functional processes in modern ecosystems, as well as to calibration efforts supporting reconstruction of past ecosystems and environments from the sedimentary archives of leaf wax biomarkers. Towards these goals, we have surveyed the distributions of leaf wax n-alkanes in trees from the lowland tropical rainforest (TR) and montane cloud forest (TMCF) of Perú. Molecular abundances were quantified via gas chromatography flame ionization detection (GC-FID) for 632 individuals, 152 species, 99 genera and 51 families across 9 forest plots spanning 0.2–3.6 km elevation. We found the expected abundance distributions; for example, they were dominated by long chain, odd numbered n-alkanes, especially C29 and C31. New observations included a tendency to increasing total alkane concentration at higher elevation. We propose that the well known leaf economic strategy to increase leaf mass per unit area with elevation, provides a theoretical basis for understanding the increase in leaf wax n-alkane abundance with elevation: we infer an increased investment in foliar defense associated with increased leaf lifespan and in response to environmental pressures including cloud immersion and declining temperature. Furthermore, we combined measurements of n-alkane concentration with estimates of forest productivity to provide new ways to quantify ecosystem-scale forest alkane productivity. We introduce a new concept of n-alkane net primary productivity (NPPalk; the product of alkane concentration and leaf NPP) and find that alkane productivity estimates range from 300 to 5000 g C/ha/yr, associated with ecological and environmental changes across the elevation profile