Molecular detection of thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease by RT-PCR

The sensitive detection of circulating tumour cells in patients with differentiated thyroid cancer may precede the detection of relapse by other diagnostic studies – such as serum thyroglobulin – and thus may have important therapeutic and prognostic implications. We performed reverse transcription-polymerase chain reaction (RT-PCR) on blood samples from patients diagnosed with thyroid disease using two different RT-PCR sensitivities. Additionally, tissue specificity of TG mRNA-expression was determined using RNA extracts from 27 different human tissues. The lower limit of detection was 50–100 TG mRNA producing cells/ml blood using a ‘normal’ RT-PCR sensitivity and 10–20 cells/ml blood using a ‘high’ sensitivity. With the normal sensitivity TG mRNA was detected in 9/13 patients with thyroid cancer and metastasis, 63/137 patients with a history of thyroid cancer and no metastasis, 21/85 with non-malignant thyroid disease and 9/50 controls. With the high sensitivity TG mRNA was detected in 11/13 patients with thyroid cancer and metastasis, 111/137 patients with a history of thyroid cancer and no metastasis, 61/85 with non-malignant thyroid disease and 41/50 controls. Interestingly, using the normal RT-PCR sensitivity TG mRNA transcripts are specific for thyroid tissue and detectable in the peripheral blood of controls and patients with thyroid disease, which correlates with a diagnosis of metastasized thyroid cancer. However, with a high RT-PCR sensitivity, TG mRNA expression was found not to be specific for thyroid tissue and was not correlated with a diagnosis of thyroid cancer in patients. As a consequence, to date TG mRNA detected by RT-PCR in the peripheral blood cannot be recommended as a tumour marker superior to TG serum-level. © 2000 Cancer Research Campaig

Active Faulting in Lake Constance (Austria, Germany, Switzerland) Unraveled by Multi-Vintage Reflection Seismic Data

Probabilistic seismic hazard assessments are primarily based on instrumentally recorded and historically documented earthquakes. For the northern part of the European Alpine Arc, slow crustal deformation results in low earthquake recurrence rates and brings up the necessity to extend our perspective beyond the existing earthquake catalog. The overdeepened basin of Lake Constance (Austria, Germany, and Switzerland), located within the North-Alpine Molasse Basin, is investigated as an ideal (neo-) tectonic archive. The lake is surrounded by major tectonic structures and constrained via the North Alpine Front in the South, the Jura fold-and-thrust belt in the West, and the Hegau-Lake Constance Graben System in the North. Several fault zones reach Lake Constance such as the St. Gallen Fault Zone, a reactivated basement-rooted normal fault, active during several phases from the Permo-Carboniferous to the Mesozoic. To extend the catalog of potentially active fault zones, we compiled an extensive 445 km of multi-channel reflection seismic data in 2017, complementing a moderate-size GI-airgun survey from 2016. The two datasets reveal the complete overdeepened Quaternary trough and its sedimentary infill and the upper part of the Miocene Molasse bedrock. They additionally complement existing seismic vintages that investigated the mass-transport deposit chronology and Mesozoic fault structures. The compilation of 2D seismic data allowed investigating the seismic stratigraphy of the Quaternary infill and its underlying bedrock of Lake Constance, shaped by multiple glaciations. The 2D seismic sections revealed 154 fault indications in the Obersee Basin and 39 fault indications in the Untersee Basin. Their interpretative linkage results in 23 and five major fault planes, respectively. One of the major fault planes, traceable to Cenozoic bedrock, is associated with a prominent offset of the lake bottom on the multibeam bathymetric map. Across this area, high-resolution single channel data was acquired and a transect of five short cores was retrieved displaying significant sediment thickness changes across the seismically mapped fault trace with a surface-rupture related turbidite, all indicating repeated activity of a likely seismogenic strike-slip fault with a normal faulting component. We interpret this fault as northward continuation of the St. Gallen Fault Zone, previously described onshore on 3D seismic data

Possible earthquake trigger for 6th century mass wasting deposit at Lake Ohrid (Macedonia/Albania)

Lake Ohrid shared by the Republics of Albania and Macedonia is formed by a tectonically active graben within the south Balkans and suggested to be the oldest lake in Europe. Several studies have shown that the lake provides a valuable record of climatic and environmental changes and a distal tephrostratigraphic record of volcanic eruptions from Italy. Fault structures identified in seismic data demonstrate that sediments have also the potential to record tectonic activity in the region. Here, we provide an example of linking seismic and sedimentological information with tectonic activity and historical documents. Historical documents indicate that a major earthquake destroyed the city of Lychnidus (today: city of Ohrid) in the early 6th century AD. Multichannel seismic profiles, parametric sediment echosounder profiles, and a 10.08m long sediment record from the western part of the lake indicate a 2m thick mass wasting deposit, which is tentatively correlated with this earthquake. The mass wasting deposit is chronologically well constrained, as it directly overlays the AD472/AD 512 tephra. Moreover, radiocarbon dates and cross correlation with other sediment sequences with similar geochemical characteristics of the Holocene indicate that the mass wasting event took place prior to the onset of the Medieval Warm Period, and is attributed it to one of the known earthquakes in the region in the early 6th century AD

Reaction of a polar gravel‐spit system to atmospheric warming and glacier retreat as reflected by morphology and internal sediment geometries (South Shetland Islands, Antarctica)

Sedimentary architecture and morphogenetic evolution of a polar bay-mouth gravel-spit system are revealed based on topographic mapping, sedimentological data, radiocarbon dating and ground-penetrating radar investigations. Data document variable rates of spit progradation in reaction to atmospheric warming synchronous to the termination of the last glacial re-advance (LGR, 0.45–0.25 ka BP), the southern hemisphere equivalent of the Little Ice Age cooling period. Results show an interruption of spit progradation that coincides with the proposed onset of accelerated isostatic rebound in reaction to glacier retreat. Spit growth resumed in the late 19th century after the rate of isostatic rebound decreased, and continues until today. The direction of modern spit progradation, however, is rotated northwards compared with the growth axis of the early post-LGR spit. This is interpreted to reflect the shift and strengthening in the regional wind field during the last century. A new concept for the interplay of polar gravel-spit progradation and glacio-isostatic adjustment is presented, allowing for the prediction of future coastal evolution in comparable polar settings

The SCOPSCO drilling project recovers more than 1.2 million years of history from Lake Ohrid

The Scientific Collaboration on Past Speciation Conditions in Lake Ohrid (SCOPSCO) project is an international research initiative to study the influence of major geological and environmental events on the biological evolution of lake taxa. SCOPSCO drilling campaigns were carried out in 2011 and 2013. In 2011 we used gravity and piston coring at one of the five proposed drill sites, and in 2013 we undertook deep drilling with the Deep Lake Drilling System (DLDS) of Drilling, Observation and Sampling of the Earth's Continental Crust (DOSECC). In April and May 2013, a total of 2100 m sediments were recovered from four drill sites with water depths ranging from 125 to 260 m. The maximum drill depth was 569 m below the lake floor in the centre of the lake. By retrieving overlapping sediment sequences, 95% of the sediment succession was recovered. Initial data from borehole logging, core logging and geochemical measurements indicate that the sediment succession covers >1.2 million years (Ma) in a quasi-continuous sequence. These early findings suggest that the record from Lake Ohrid will substantially improve the knowledge of long-term environmental change and short-term geological events in the northeastern Mediterranean region, which forms the basis for improving understanding of the influence of major geological and environmental events on the biological evolution of endemic species

Challenging cisgenderism through trans people's narratives of domestic violence and abuse

By drawing on empirical research that explored trans people’s experiences of domestic violence and abuse (DVA), this paper problematises the ‘gender asymmetry debate' in DVA discourse. It does so by highlighting cisgenderism and a heteronormative bias which have led to the invisibility of a trans perspective. Qualitative data was collected via narrative interviews and this was examined using a voice-centred relational technique. A total of twenty four interviews were undertaken with trans people (n = 15) and domestic abuse practitioners (n = 9). In relation to the presentation and impact of DVA, and in the context of trans and cisgender people's abuse experiences, the research findings report both similarities and differences. Four narratives are presented here to illuminate both. This paper adds new insight and challenges normative and dominant discourses by promoting the need for further theorising about the gendered nature of domestic violence and abuse

Postglacial evolution of Lake Constance: sedimentological and geochemical evidence from a deep-basin sediment core

The modern, over 250-m-deep basin of Lake Constance represents the underfilled northern part of an over 400-m-deep, glacially overdeepened trough, which reaches well into the Alps at its southern end. The overdeep- ening was formed by repeated glacial advance-retreat cycles of the Rhine Glacier throughout the Middle to Late Pleistocene. A seismic survey of Lake Constance revealed a Quaternary sediment fill of more than 150 m thickness representing at least the last glacial cycle. The stratified sedimentary fill consists at the base of ice-contact deposits on top of the molasse bedrock, overlain by glaciolacustrine to lacustrine sediments. During the successful field test of a newly developed, mid-size coring system ("HIPERCORIG"), the longest core (HIBO19) ever taken in Lake Constance was retrieved with an overall length of 24 m. The sediments recovered consist of a nearly continuous succession of lacustrine silts and sands including more than 12 m of Late Glacial sediment at the base. 14 lithotypes were identified through petrophysical and geochemical analyses. In combination with a 14C- and OSL-based age-depth model, the core was divided into three main chronostratigraphic units. The basal age of ~ 13.7 ka BP dates the base of the succes- sion back to the Bølling-Allerød interstadial, with overlying strata representing a complete and thick Younger-Dryas to Holocene succession. The sediments offer a high-resolution insight into the evolution of paleo-Lake Constance from a cold, postglacial to a more productive and warmer Holocene lake. The Late Glacial succession is dominated by massive, m-thick sand beds reflecting episodic sedimentation pulses. They are most likely linked to a subaquatic channel system originating in the river Seefelder Aach, which is, despite the Holocene drape, still apparent in today’s lake bathymetry. The overlying Holocene succession reveals a prominent, several cm-thick, double-turbiditic event layer representing the most distal impact of the Flimser Bergsturz, the largest known rockslide of the Alps that occurred over 100 km upstream the river Rhine at ~ 9.5 ka BP. Furthermore, lithologic variations in the Holocene succession document the varying sediment loads of the river Rhine and the endogenic production representing a multitude of environmental changes

Acute-Phase-HDL Remodeling by Heparan Sulfate Generates a Novel Lipoprotein with Exceptional Cholesterol Efflux Activity from Macrophages

During episodes of acute-inflammation high-density lipoproteins (HDL), the carrier of so-called good cholesterol, experiences a major change in apolipoprotein composition and becomes acute-phase HDL (AP-HDL). This altered, but physiologically important, HDL has an increased binding affinity for macrophages that is dependent on cell surface heparan sulfate (HS). While exploring the properties of AP-HDL∶HS interactions we discovered that HS caused significant remodeling of AP-HDL. The physical nature of this change in structure and its potential importance for cholesterol efflux from cholesterol-loaded macrophages was therefore investigated. In the presence of heparin, or HS, AP-HDL solutions at pH 5.2 became turbid within minutes. Analysis by centrifugation and gel electrophoresis indicated that AP-HDL was remodeled generating novel lipid poor particles composed only of apolipoprotein AI, which we designate β2. This remodeling is dependent on pH, glycosaminoglycan type, is promoted by Ca2+ and is independent of protease or lipase activity. Compared to HDL and AP-HDL, remodeled AP-HDL (S-HDL-SAA), containing β2 particles, demonstrated a 3-fold greater cholesterol efflux activity from cholesterol-loaded macrophage. Because the identified conditions causing this change in AP-HDL structure and function can exist physiologically at the surface of the macrophage, or in its endosomes, we postulate that AP-HDL contains latent functionalities that become apparent and active when it associates with macrophage cell surface/endosomal HS. In this way initial steps in the reverse cholesterol transport pathway are focused at sites of injury to mobilize cholesterol from macrophages that are actively participating in the phagocytosis of damaged membranes rich in cholesterol. The mechanism may also be of relevance to aspects of atherogenesis

FimH Adhesin of Type 1 Fimbriae Is a Potent Inducer of Innate Antimicrobial Responses Which Requires TLR4 and Type 1 Interferon Signalling

Components of bacteria have been shown to induce innate antiviral immunity via Toll-like receptors (TLRs). We have recently shown that FimH, the adhesin portion of type 1 fimbria, can induce the innate immune system via TLR4. Here we report that FimH induces potent in vitro and in vivo innate antimicrobial responses. FimH induced an innate antiviral state in murine macrophage and primary MEFs which was correlated with IFN-β production. Moreover, FimH induced the innate antiviral responses in cells from wild type, but not from MyD88−/−, Trif−/−, IFN−α/βR−/− or IRF3−/− mice. Vaginal delivery of FimH, but not LPS, completely protected wild type, but not MyD88−/−, IFN-α/βR−/−, IRF3−/− or TLR4−/− mice from subsequent genital HSV-2 challenge. The FimH-induced innate antiviral immunity correlated with the production of IFN-β, but not IFN-α or IFN-γ. To examine whether FimH plays a role in innate immune induction in the context of a natural infection, the innate immune responses to wild type uropathogenic E. coli (UPEC) and a FimH null mutant were examined in the urinary tract of C57Bl/6 (B6) mice and TLR4-deficient mice. While UPEC expressing FimH induced a robust polymorphonuclear response in B6, but not TLR4−/− mice, mutant bacteria lacking FimH did not. In addition, the presence of TLR4 was essential for innate control of and protection against UPEC. Our results demonstrate that FimH is a potent inducer of innate antimicrobial responses and signals differently, from that of LPS, via TLR4 at mucosal surfaces. Our studies suggest that FimH can potentially be used as an innate microbicide against mucosal pathogens

NEXAFS Sensitivity to Bond Lengths in Complex Molecular Materials: A Study of Crystalline Saccharides

Detailed analysis of the C K near-edge X-ray absorption fine structure (NEXAFS) spectra of a series of saccharides (fructose, xylose, glucose, galactose, maltose monohydrate, α-lactose monohydrate, anhydrous β-lactose, cellulose) indicates that the precise determination of IPs and σ* shape resonance energies is sensitive enough to distinguish different crystalline saccharides through the variations in their average C–OH bond lengths. Experimental data as well as FEFF8 calculations confirm that bond length variations in the organic solid state of 10–2 Å can be experimentally detected, opening up the possibility to use NEXAFS for obtaining incisive structural information for molecular materials, including noncrystalline systems without long-range order such as dissolved species in solutions, colloids, melts, and similar amorphous phases. The observed bond length sensitivity is as good as that originally reported for gas-phase and adsorbed molecular species. NEXAFS-derived molecular structure data for the condensed phase may therefore be used to guide molecular modeling as well as to validate computationally derived structure models for such systems. Some results indicate further analytical value in that the σ* shape resonance analysis may distinguish hemiketals from hemiacetals (i.e., derived from ketoses and aldoses) as well as α from β forms of otherwise identical saccharides