Alamance County Archaeological Survey Project, Alamance County, North Carolina

Research Report No. 5, Research Laboratories of Archaeology, University of North Carolina at Chapel Hill. Reports in this series discuss the findings of archaeological excavations and research projects undertaken by the RLA between 1984 and present

Geochemical observations on Hydrate Ridge, Cascadia Margin during R/V BROWN-ROPOS cruise : August 1998

A massive release of methane on the Cascadia Hydrate Ridge was documented during a ROPOS program in August 1998, consistent with previously reported observations in 1996. An extensive survey of the seafloor revealed that the seeps lie within a narrow band trending 109 degrees. This feature parallels larger mounds imaged by Seabeam as well as larger structures of the accretionary prism such as the Daisy bank. The area of intense bubbling is characterized by extensive bacterial mats. Large clam fields were observed ten's of meters away from the gas seeps. A third province with carbonate blocks but no clams or bacterial mats was mapped approximately 200 meters away from the seeps. To constrain fluid flow through the sediments, we deployed 8 osomotic flow meters. The areas of gas discharge are discrete and highly focussed within conduits with an approximate cross-sectional area of 5 cm2. We estimate the gas flow rate to be on the order of 5 liters/minute. While the subsurface plumbing is unknown, the high flow rate of the sampled gas seep suggests a very short transit time from the gas source (presumably the base of the BSR at 70 mbsf) to the sea floor. The Rn/CH4 ratio in gas samples collected from the gas vents is very high, approximately 50 dpm/liter (stp) CH4. Using these values, we estimate that the time required for the fluids to transit 70 m is approximately 1 hour. To further constrain the nature of the discharging fluids, we will analyze samples for their elemental and isotopic composition. Methane hydrate should be stable at the temperature and pressure conditions at the seafloor on Hydrate Ridge. Indeed, solid hydrate was observed to form within the gas samplers as well as on the camera itself, supporting the conclusion that methane is rapidly transported to the seafloor from beneath the BSR within discrete conduits, most likely separated from significant amounts of pore water. When discharged at the seafloor, some of the methane precipitate as hydrate and some continues to rise within the water column. Bubbles were observed with the ROV up to 50 meters above the seafloor. This methane generates a plume in the water column, which was first documented during the 1996 GEOMAR survey. The most pronounced methane plumes observed during 1998 occur nearest to the active discharge sites, where methane concentrations up to 800 nmol/l were recorded

Differential effects of EPA vs. DHA on postprandial vascular function and the plasma oxylipin profile in men

Our objective was to investigate the impact of EPA versus DHA, on arterial stiffness and reactivity, and underlying mechanisms (with a focus on plasma oxylipins), in the postprandial state. In a 3-arm cross-over acute test meal trial men (n=26, 35-55y) at increased CVD risk, received a high fat (42.4g) test meal providing 4.16 g of EPA or DHA or control oil in random order. At 0 h and 4 h, blood samples were collected to quantify plasma fatty acids, LCn-3PUFAs derived oxylipins, nitrite and hydrogen sulfide and serum lipids and glucose. Vascular function was assessed using blood pressure, Reactive Hyperaemia Index (RHI), Pulse Wave Velocity and Augmentation Index (AIx). The DHA-rich oil significantly reduced AIx by 13% (P=0.047) with the decrease following EPA-rich oil intervention not reaching statistical significance. Both interventions increased EPA and DHA derived oxylipins in the acute postprandial state, with an (1.3 fold) increase in 19,20-DiHDPA evident after DHA intervention (P < 0.001). In conclusion, a single dose of DHA significantly improved postprandial arterial stiffness as assessed by AIx, which if sustained would be associated with a significant decrease in CVD risk. The observed increases in oxylipins provide a mechanistic insight for the AIx effect

Geochemical observations on Hydrate Ridge, Cascadia Margin : July 1999

Geophysical and biogeochemical processes associated with fluid venting from active and passive continental margins will receive significant scientific and economic attention into the next century and are of major societal relevance. An important unknown among these interrelated processes is the role played by methane gas hydrates, at and below the seafloor, and their impact on the oceans and atmosphere. Research scientists from institutions in the USA, Germany and Canada have developed a research project dedicated to a long-term study of continental margin gas hydrates on the Cascadia Accretionary Prism, under the acronym "TECFLUX". It is conceived as multi-stage research effort with the eventual goal of measuring the energy and chemical fluxes associated with this system, determining its temporal variability in response to tectonic and oceanographic forcing, and evaluating its impact on marine biogeochemical cycles

Bidirectional Transcription Directs Both Transcriptional Gene Activation and Suppression in Human Cells

Small RNAs targeted to gene promoters in human cells have been shown to modulate both transcriptional gene suppression and activation. However, the mechanism involved in transcriptional activation has remained poorly defined, and an endogenous RNA trigger for transcriptional gene silencing has yet to be identified. Described here is an explanation for siRNA-directed transcriptional gene activation, as well as a role for non-coding antisense RNAs as effector molecules driving transcriptional gene silencing. Transcriptional activation of p21 gene expression was determined to be the result of Argonaute 2–dependent, post-transcriptional silencing of a p21-specific antisense transcript, which functions in Argonaute 1–mediated transcriptional control of p21 mRNA expression. The data presented here suggest that in human cells, bidirectional transcription is an endogenous gene regulatory mechanism whereby an antisense RNA directs epigenetic regulatory complexes to a sense promoter, resulting in RNA-directed epigenetic gene regulation. The observations presented here support the notion that epigenetic silencing of tumor suppressor genes, such as p21, may be the result of an imbalance in bidirectional transcription levels. This imbalance allows the unchecked antisense RNA to direct silent state epigenetic marks to the sense promoter, resulting in stable transcriptional gene silencing

PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further PsA-specific risk locus

Objectives Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis; it has a higher estimated genetic component than psoriasis alone, however most genetic susceptibility loci identified for PsA to date are also shared with psoriasis. Here we attempt to validate novel single nucleotide polymorphisms selected from our recent PsA Immunochip study and determine specificity to PsA. Methods A total of 15 single nucleotide polymorphisms were selected (PImmunochip <1×10−4) for validation genotyping in 1177 cases and 2155 controls using TaqMan. Meta-analysis of Immunochip and validation data sets consisted of 3139 PsA cases and 11 078 controls. Novel PsA susceptibility loci were compared with data from two large psoriasis studies (WTCCC2 and Immunochip) to determine PsA specificity. Results We found genome-wide significant association to rs2476601, mapping to PTPN22 (p=1.49×10−9, OR=1.32), but no evidence for association in the psoriasis cohort (p=0.34) and the effect estimates were significantly different between PsA and psoriasis (p=3.2×10−4). Additionally, we found genome-wide significant association to the previously reported psoriasis risk loci; NOS2 (rs4795067, p=5.27×10−9). Conclusions For the first time, we report genome-wide significant association of PTPN22 (rs2476601) to PsA susceptibility, but no evidence for association to psoriasis

South Atlantic intermediate water advances into the North-east Atlantic with reduced Atlantic meridional overturning circulation during the last glacial period

The Nd isotopic composition (epsilon Nd) of seawater and cold-water coral (CWC) samples from the Gulf of Cadiz and the Alboran Sea, at a depth of 280-827 m were investigated in order to constrain middepth water mass dynamics within the Gulf of Cadiz over the past 40 ka. epsilon Nd of glacial and Holocene CWC from the Alboran Sea and the northern Gulf of Cadiz reveals relatively constant values (-8.6 to -9.0 and -9.5 to -10.4, respectively). Such values are similar to those of the surrounding present-day middepth waters from the Mediterranean Outflow Water (MOW; epsilon Nd approximate to -9.4) and Mediterranean Sea Water (MSW; epsilon Nd approximate to -9.9). In contrast, glacial epsilon Nd values for CWC collected at thermocline depth (550-827 m) in the southern Gulf of Cadiz display a higher average value (-8.90.4) compared to the present-day value (-11.70.3). This implies a higher relative contribution of water masses of Mediterranean (MSW) or South Atlantic origin (East Antarctic Intermediate Water, EAAIW). Our study has produced the first evidence of significant radiogenic epsilon Nd values (approximate to -8) at 19, 23-24, and 27 ka, which are coeval with increasing iceberg discharges and a weakening of Atlantic Meridional Overturning Circulation (AMOC). Since MOW epsilon Nd values remained stable during the last glacial period, it is suggested that these radiogenic epsilon Nd values most likely reflect an enhanced northward propagation of glacial EAAIW into the eastern Atlantic Basin

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders

Funder: Kennedy Trust Rheumatology Research Prize StudentshipFunder: DFG Cluster of Excellence “Precision Medicine in Chronic In-flammation” (PMI; ID: EXC2167)Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: “Ideas” Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNLFunder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421Abstract: Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS