Distal volcanic ash layers in the Lateglacial Interstadial (GI-1): problems of stratigraphic discrimination

A new Icelandic ash layer has been detected in mid-Interstadial sediments in a number of Scottish Lateglacial sequences and has been named the Penifiler Tephra. It is rhyolitic in composition and possesses a chemistry, which is similar to the Borrobol Tephra of early Lateglacial Interstadial age, which also occurs in a number of these same sequences. Where the Borrobol Tephra has been identified in these sequences it consistently exhibits a diffuse distribution accompanied in some cases by stratigraphic bimodality. A number of sedimentological and taphonomic factors are considered in order to account for this distribution. One possibility is that these distributions are produced by taphonomic factors. Another possibility is that the Borrobol Tephra may not be the product of a single Icelandic eruption, but of two events closely spaced in time. In at least two of the sequences investigated in this study, basaltic shards were found in association with the Penifiler and Borrobol tephras, suggesting either a basaltic phase associated with these eruptions, or coincident eruptions from a separate basaltic volcanic centre. The discovery of the new Penifiler Tephra makes a contribution to the regional tephrostratigraphic framework, and provides an additional isochron for assessing the synchroneity of palaeoenvironmental changes during the Interstadial. The true stratigraphic nature and age of the Borrobol Tephra, however, remains unresolved and, therefore, its use as an isochron is more problematic. The possible occurrence of basaltic populations may strengthen correlations with basaltic tephras recently detected in the NGRIP ice-core.

Three new distal tephras in sediments spanning the Last Glacial-Interglacial Transition in Scotland

Three new microtephras are reported from a number of lake sites from the Inner Hebrides and Scottish mainland. One occurs stratigrapically in the middle of Greenland Interstadial 1 (GI-1) and has been named the Penifiler Tephra. It is rhyolitic and possesses a geochemical signature that is very similar to that of the Borrobol Tephra, which also occurs in three of the sequences reported here, but which lies close to the lower boundary of GI-1. The second occurs stratigraphically in the early Holocene below the Saksunarvatn Ash and is named the Ashik Tephra. This tephra is geochemically bimodal, with a rhyolitic component comparable to the An Druim Tephra that occurs later in the Holocene, and a basaltic component which is similar to the Saksunarvatn Ash. A third tephra occurs stratigraphically above the Saksunarvatn Ash and is provisionally named the Breakish Tephra. The consistent inter-site correlation demonstrated for these new tephras at several sites enhances the regional tephrostratigraphic framework, and increases the potential for correlating palaeoenvironmental events during GI-1 and the early Holocene. However, the occurrence of multiple tephras with similar geochemistry in close stratigraphic and temporal proximity has implications for the rigour with which tephrostratigraphic investigations must be performed.

A new and less destructive laboratory procedure for the physical separation of distal glass tephra shards from sediments

Tephrochronology, a key tool in the correlation of Quaternary sequences, relies on the extraction of tephra shards from sediments for visual identification and high-precision geochemical comparison. A prerequisite for the reliable correlation of tephra layers is that the geochemical composition of glass shards remains unaltered by natural processes (e.g. chemical exchange in the sedimentary environment) and/or by laboratory analytical procedures. However, natural glasses, particularly when in the form of small shards with a high surface to volume ratio, are prone to chemical alteration in both acidic and basic environments. Current techniques for the extraction of distal tephra from sediments involve the ‘cleaning’ of samples in precisely such environments and at elevated temperatures. The acid phase of the ‘cleaning’ process risks alteration of the geochemical signature of the shards, while the basic phase leads to considerable sample loss through dissolution of the silica network. Here, we illustrate the degree of alteration and loss to which distal tephras may be prone, and introduce a less destructive procedure for their extraction. This method is based on stepped heavy liquid flotation and which results in samples of sufficient quality for analysis while preserving their geochemical integrity. In trials, this method out-performed chemical extraction procedures in terms of the number of shards recovered and has resulted in the detection of new tephra layers with low shard concentrations. The implications of this study are highly significant because (i) the current database of distal tephra records and their corresponding geochemical signatures may require refinement and (ii) the record of distal tephras may be incomplete due to sample loss induced by corrosive laboratory procedures. It is therefore vital that less corrosive laboratory procedures are developed to make the detection and classification of distal glass tephra more secure.

Detection of Lateglacial distal tephra layers in the Netherlands

Three distal tephra layers or cryptotephras have been detected within a sedimentary sequence from the Netherlands that spans the last glacial-interglacial transition. Geochemical analyses identify one as the Vedde Ash, which represents the southernmost discovery of this mid-Younger Dryas tephra so far. This tephra was found as a distinct horizon in three different cores sampled within the basin. The remaining two tephras have not been geochemically ‘fingerprinted’, partly due to low concentrations and uneven distributions of shards within the sequences sampled. Nevertheless, there is the potential for tracing these tephra layers throughout the Netherlands and into other parts of continental Europe. Accordingly, the possibilities for precise correlation of Dutch palaeoenvironmental records with other continental, marine and ice-core records from the North Atlantic region are highlighted.

Functional and genetic analysis of the colon cancer network

Cancer is a complex disease that has proven to be difficult to understand on the single-gene level. For this reason a functional elucidation needs to take interactions among genes on a systems-level into account. In this study, we infer a colon cancer network from a large-scale gene expression data set by using the method BC3Net. We provide a structural and a functional analysis of this network and also connect its molecular interaction structure with the chromosomal locations of the genes enabling the definition of cis- and trans-interactions. Furthermore, we investigate the interaction of genes that can be found in close neighborhoods on the chromosomes to gain insight into regulatory mechanisms. To our knowledge this is the first study analyzing the genome-scale colon cancer network.

Immunohistochemical study of pig retinal development

PURPOSE: The pig eye is similar to the human eye in terms of anatomy, vasculature, and photoreceptor distribution, and therefore provides an attractive animal model for research into retinal disease. The purpose of this study was to characterize retinal histology in the developing and mature pig retina using antibodies to well established retinal cell markers commonly used in rodents.

METHODS: Eyes were enucleated from fetuses in the 9th week of gestation, 1 week old piglets and 6 months old adult animals. Eyeglobes were fixed and cryosectioned. A panel of antibodies to well established retinal markers was employed for immunohistochemistry. Fluorescently labeled secondary antibodies were used for signal detection, and images were acquired by confocal microscopy. Mouse retina at postnatal day (P) 5 was used as a reference for this study to compare progression of histogenesis. Most of the primary antibodies have previously been used on mouse tissue.

RESULTS: Most of the studied markers were detected in midgestation pig retina, and the majority had a similar distribution in pig as in P5 mouse retina. However, rhodopsin immunolabeling was detected in pig retina at midgestation but not in P5 mouse retina. Contrary to findings in all rodents, horizontal cells were Islet1-positive and cones were calbindin-immunoreactive in pig retina, as has also been shown for the primate retina. Recoverin and rhodopsin immunolabeling revealed an increase in the length of photoreceptor segments in 6 months, compared to 1 week old animals.

CONCLUSIONS: Comparison with the published data on human retina revealed similar marker distribution and histogenesis progression in the pig and human retina, supporting the pig as a valuable animal model for studies on retinal disease and repair. Furthermore, this study provides information about the dynamics of retinal histogenesis in the pig and validates a panel of antibodies that reliably detects developing and mature retinal cell phenotypes in the pig retina.

Sphingosine Kinase 1 Promotes Malignant Progression in Colon Cancer and Independently Predicts Survival of Patients With Colon Cancer by Competing Risk Approach in South Asian Population

OBJECTIVES: Sphingosine kinase 1 (SphK1) phosphorylates the membrane sphingolipid, sphingosine, to sphingosine-1-phosphate (S1P), an oncogenic mediator, which drives tumor cell growth and survival. Although SphK1 has gained increasing prominence as an oncogenic determinant in several cancers, its potential as a therapeutic target in colon cancer remains uncertain. We investigated the clinical relevance of SphK1 expression in colon cancer as well as its inhibitory effects in vitro.

METHODS: SphK1 expression in human colon tumor tissues was determined by immunohistochemistry and its clinicopathological significance was ascertained in 303 colon cancer cases. The effects of SphK1 inhibition on colon cancer cell viability and the phosphoinositide 3-kinase (PI3K)/Akt cell survival pathway were investigated using a SphK1-selective inhibitor-compound 5c (5c). The cytotoxicity of a novel combination using SphK1 inhibition with the chemotherapeutic drug, 5-fluorouracil (5-FU), was also determined.

RESULTS: High SphK1 expression correlated with advanced tumor stages (AJCC classification). Using a competing risk analysis model to take into account disease recurrence, we found that SphK1 is a significant independent predictor for mortality in colon cancer patients. In vitro, the inhibition of SphK1 induced cell death in colon cancer cell lines and attenuated the serum-dependent PI3K/Akt signaling. Inhibition of SphK1 also enhanced the sensitivity of colon cancer cells to 5-FU.

CONCLUSION: Our findings highlight the impact of SphK1 in colon cancer progression and patient survival, and provide evidence supportive of further development in combination strategies that incorporate SphK1 inhibition with current chemotherapeutic agents to improve colon cancer outcomes.

Distal tephrochronology in volcanic regions: Challenges and insights from Kamchatkan lake sediments

Kamchatka is one of the world’s most active volcanic regions and has hosted many explosive eruptions during the Holocene. These eruptions had the potential to disperse tephra over wide areas, forming time-synchronous markers wherever those tephras are found. Recent research in Kamchatka has begun to focus on the geochemical analysis of individual glass shards in order to characterise tephra layers. We have applied this approach to the study of visible tephras from three lakes – one in central and two in northern Kamchatka – with the aim of identifying key tephras and potential issues in the application of distal (>100 km from an active volcano) tephra in volcanically complex regions. In total, 23 tephras from 22 tephra beds have been geochemically analysed, representing products from at least four volcanic systems in Kamchatka. We demonstrate that distal lake sediments in the region can yield reliable tephrostratigraphies, capturing tephra from eruptions that have the greatest potential to disperse volcanic ash beyond the region. We draw attention to issues relating to correlating and distinguishing key marker horizons from the highly active Shiveluch Volcano, namely the need to ensure inter-lab comparability of geochemical data and good chronological control of the proximal and distal tephras. Importantly, we have also extended the known distribution of two key tephra isochrons from the Ksudach volcano. Our work contributes valuable glass geochemical on data several key marker beds that will facilitate future tephra and palaeoenvironmental research within and beyond Kamchatka.

The significance of combining VEGFA, FLT1, and KDR expressions in colon cancer patient prognosis and predicting response to bevacizumab

Targeting angiogenesis through inhibition of the vascular endothelial growth factor (VEGF) pathway has been successful in the treatment of late stage colorectal cancer. However, not all patients benefit from inhibition of VEGF. Ras status is a powerful biomarker for response to anti-epidermal growth factor receptor therapy; however, an appropriate biomarker for response to anti-VEGF therapy is yet to be identified. VEGF and its receptors, FLT1 and KDR, play a crucial role in colon cancer progression; individually, these factors have been shown to be prognostic in colon cancer; however, expression of none of these factors alone was predictive of tumor response to anti-VEGF therapy. In the present study, we analyzed the expression levels of VEGFA, FLT1, and KDR in two independent colon cancer datasets and found that high expression levels of all three factors afforded a very poor prognosis. The observation was further confirmed in another independent colon cancer dataset, wherein high levels of expression of this three-gene signature was predictive of poor prognosis in patients with proficient mismatch repair a wild-type KRas status, or mutant p53 status. Most importantly, this signature also predicted tumor response to bevacizumab, an antibody targeting VEGFA, in a cohort of bevacizumab-treated patients. Since bevacizumab has been proven to be an important drug in the treatment of advanced stage colon cancer, our results suggest that the three-gene signature approach is valuable in terms of its prognostic value, and that it should be further evaluated in a prospective clinical trial to investigate its predictive value to anti-VEGF treatment.

Exceptionally Long Distance Transport of Volcanic Ash: Implications for Stratigraphy, Hazards and the Sourcing of Distal Tephra Deposits

Cryptotephras (tephra not visible to the naked eye) form the foundation of the tephrostratigraphic frameworks used in Europe to date and correlate widely distributed geologic, paleoenvironmental and archaeological records. Pyne-O'Donnell et al. (2012) established the potential for developing a similar crypto-tephrostratigraphy across eastern North America by identifying multiple tephra, including the White River Ash (east; WRAe), St. Helens We and East Lake, in a peat core located in Newfoundland. Following on from this work, several ongoing projects have examined additional peat cores from Michigan, New York State, Maine, Nova Scotia and Newfoundland to build a tephrostratigraphic framework for this region. Using the precedent set by recent research by Jensen et al.(in press) that correlated the Alaskan WRAe to the European cryptotephra AD860B, unknown tephras identified in this work were not necessarily assumed to be from "expected" source areas (e.g. the Cascades). Here we present several examples of the preservation of tephra layers with an intercontinental distribution (i.e. WRAe and Ksudach 1), from relatively small magnitude events (i.e. St. Helens layer T, Mono Crater), and the first example of a Mexican ash in the NE (Volcan Ceboruco, Jala pumice). There are several implications of the identification of these units. These far-travelled ashes: (1) highlight the need to consider "ultra" distal source volcanoes for unknown cryptotephra deposits,. (2) present an opportunity for physical volcanologists to examine why some eruptions have an exceptional distribution of ash that is not necessarily controlled by the magnitude of the event. (3) complicate the idea of using tephrostratigraphic frameworks to understand the frequency of eruptions towards aiding hazard planning and prediction (e.g. Swindles et al., 2011). (4) show that there is a real potential to link tropical and mid to high-latitude paleoenvironmental records. Jensen et al. (in press) Transatlantic correlation of the Alaskan White River Ash. Geology. Pyne-O'Donnell et al. (2012). High-precision ultra-distal Holocene tephrochronology in North America. Quaternary Science Reviews, 52, 6-11. Swindles et al. (2011). A 7000 yr perspective on volcanic ash clouds affecting northern Europe. Geology, 39, 887-890.