Minaw and Neil McKenzie to Mr. Meredith (2 October 1962)

https://egrove.olemiss.edu/mercorr_pro/1447/thumbnail.jp

Protein Kinase A Activity and Anchoring Are Required for Ovarian Cancer Cell Migration and Invasion

Epithelial ovarian cancer (EOC) is the deadliest of the gynecological malignancies, due in part to its clinically occult metastasis. Therefore, understanding the mechanisms governing EOC dissemination and invasion may provide new targets for antimetastatic therapies or new methods for detection of metastatic disease. The cAMP-dependent protein kinase (PKA) is often dysregulated in EOC. Furthermore, PKA activity and subcellular localization by A-kinase anchoring proteins (AKAPs) are important regulators of cytoskeletal dynamics and cell migration. Thus, we sought to study the role of PKA and AKAP function in both EOC cell migration and invasion. Using the plasma membrane-directed PKA biosensor, pmAKAR3, and an improved migration/invasion assay, we show that PKA is activated at the leading edge of migrating SKOV-3 EOC cells, and that inhibition of PKA activity blocks SKOV-3 cell migration. Furthermore, we show that while the PKA activity within the leading edge of these cells is mediated by anchoring of type-II regulatory PKA subunits (RII), inhibition of anchoring of either RI or RII PKA subunits blocks cell migration. Importantly, we also show – for the first time – that PKA activity is up-regulated at the leading edge of SKOV-3 cells during invasion of a three-dimensional extracellular matrix and, as seen for migration, inhibition of either PKA activity or AKAP-mediated PKA anchoring blocks matrix invasion. These data are the first to demonstrate that the invasion of extracellular matrix by cancer cells elicits activation of PKA within the invasive leading edge and that both PKA activity and anchoring are required for matrix invasion. These observations suggest a role for PKA and AKAP activity in EOC metastasis

Healthy lifestyle and risk of breast cancer for indigenous and non-indigenous women in New Zealand: a case control study.

BACKGROUND: The reasons for the increasing breast cancer incidence in indigenous Māori compared to non-Māori New Zealand women are unknown. The aim of this study was to assess the association of an index of combined healthy lifestyle behaviours with the risk of breast cancer in Māori and non-Māori women. METHODS: A population-based case-control study was conducted, including breast cancer cases registered in New Zealand from 2005-2007. Controls were matched by ethnicity and 5-year age bands. A healthy lifestyle index score (HLIS) was generated for 1093 cases and 2118 controls, based on public health and cancer prevention recommendations. The HLIS was constructed from eleven factors (limiting red meat, cream, and cheese; consuming more white meat, fish, fruit and vegetables; lower alcohol consumption; not smoking; higher exercise levels; lower body mass index; and longer cumulative duration of breastfeeding). Equal weight was given to each factor. Logistic regression was used to estimate the associations between breast cancer and the HLIS for each ethnic group stratified by menopausal status. RESULTS: Among Māori, the mean HLIS was 5.00 (range 1-9); among non-Māori the mean was 5.43 (range 1.5-10.5). There was little evidence of an association between the HLIS and breast cancer for non-Māori women. Among postmenopausal Māori, those in the top HLIS tertile had a significantly lower odds of breast cancer (Odds Ratio 0.47, 95% confidence interval 0.23-0.94) compared to those in the bottom tertile. CONCLUSION: These findings suggest that healthy lifestyle recommendations could be important for reducing breast cancer risk in postmenopausal Māori women

EM-Cube: An Architecture for Low-Cost Real-Time Volume Rendering

EM-Cube is a VLSI architecture for low-cost, high quality volume rendering at full video frame rates. Derived from the Cube-4 architecture developed at SUNY at Stony Brook, EM-Cube computes sample points and gradients on-the-fly to project 3-dimensional volume data onto 2-dimensional images with realistic lighting and shading. A modest rendering system based on EM-Cube consists of a PCI card with four rendering chips (ASICs), four 64Mbit SDRAMs to hold the volume data, and four SRAMs to capture the rendered image. The performance target for this configuration is to render images from a 256^3 x 16 bit data set at 30 frames/sec. The EM-Cube architecture can be scaled to larger volume data-sets and/or higher frame rates by adding additional ASICs, SDRAMs, and SRAMs. This paper addresses three major challenges encountered developing EM-Cube into a practical product: exploiting the bandwidth inherent in the SDRAMs containing the volume data, keeping the pin-count between adjacent ASICs at a tractable level, and reducing the on-chip storage required to hold the intermediate results of rendering.Engineering and Applied Science

Sex differences in exercise-induced diaphragmatic fatigue in endurance-trained athletes

There is evidence that female athletes may be more susceptible to exercise-induced arterial hypoxemia and expiratory flow limitation and have greater increases in operational lung volumes during exercise relative to men. These pulmonary limitations may ultimately lead to greater levels of diaphragmatic fatigue in women. Accordingly, the purpose of this study was to determine whether there are sex differences in the prevalence and severity of exercise-induced diaphragmatic fatigue in 38 healthy endurance-trained men (n = 19; maximal aerobic capacity = 64.0 ± 1.9 ml·kg–1·min–1) and women (n = 19; maximal aerobic capacity = 57.1 ± 1.5 ml·kg–1·min–1). Transdiaphragmatic pressure (Pdi) was calculated as the difference between gastric and esophageal pressures. Inspiratory pressure-time products of the diaphragm and esophagus were calculated as the product of breathing frequency and the Pdi and esophageal pressure time integrals, respectively. Cervical magnetic stimulation was used to measure potentiated Pdi twitches (Pdi,tw) before and 10, 30, and 60 min after a constant-load cycling test performed at 90% of peak work rate until exhaustion. Diaphragm fatigue was considered present if there was a 15% reduction in Pdi,tw after exercise. Diaphragm fatigue occurred in 11 of 19 men (58%) and 8 of 19 women (42%). The percent drop in Pdi,tw at 10, 30, and 60 min after exercise in men (n = 11) was 30.6 ± 2.3, 20.7 ± 3.2, and 13.3 ± 4.5%, respectively, whereas results in women (n = 8) were 21.0 ± 2.1, 11.6 ± 2.9, and 9.7 ± 4.2%, respectively, with sex differences occurring at 10 and 30 min (P < 0.05). Men continued to have a reduced contribution of the diaphragm to total inspiratory force output (pressure-time product of the diaphragm/pressure-time product of the esophagus) during exercise, whereas diaphragmatic contribution in women changed very little over time. The findings from this study point to a female diaphragm that is more resistant to fatigue relative to their male counterparts

Late Holocene Sedimentation and Paleoenvironmental History for the Tidal Marshes of the Potomac and Rappahannock Rivers, Tributaries to Chesapeake Bay

Instrumental tide gauge records indicate that the modern rates of sea-level rise in the Chesapeake Bay more than double the global average of 1.2-1.5 mm yr-1. The primary objective for this study is to establish a relative depositional history for the tidal marshes of the Potomac and Rappahannock Rivers that will help us improve our understanding of processes that influence sedimentation in the proximal tributaries of Chesapeake Bay. Marsh cores were collected from Blandfield Point VA, Tappahannock VA, and Potomac Creek VA. The sedimentary facies include: 1) a lower unit of organic-poor, grey clay with fine sand and silt layers and estuarine foraminifera; and 2) an upper unit of organic-rich clay and peat with abundant brackish to freshwater marsh foraminifera and thecamoebians. AMS 14C dating of bulk marsh sediments yield sedimentation rates at Potomac Creek ranging from 3.04-4.20 mm yr-1 for the past 2500 years. Rates of sedimentation calculated for Blandfield Point indicate 1.37-2.19 mm yr-1 in the basal clays and peat for the past ~3000 years. Foraminiferal census counts indicate a freshening upward trend with a transition from an estuarine Ammobaculites crassus assemblage to a marsh Ammoastuta salsa assemblage with abundant freshwater thecamoebians. The late Holocene history of sedimentation for the marshes indicates that differential compaction, recent land use practices, and climate change have contributed to the resultant freshening-upward environmental trend and variability in sediment accumulation rates between coring sites

Gender differences in structural and attitudinal barriers to mental healthcare in UK Armed Forces personnel and veterans with self-reported mental health problems

Purpose: Structural and attitudinal barriers often hinder treatment-seeking for mental health problems among members of the Armed Forces. However, little is known about potential gender differences in structural and attitudinal barriers among members of the UK Armed Forces. The current study aimed to explore how men and women differ in terms of these barriers to care among a sample of UK Armed Forces personnel and veterans with self-reported mental health problems. Methods: Currently serving and ex-serving members of the UK Armed Forces who self-reported a mental health problem were invited to participate in a semi-structured phone interview on mental health and treatment-seeking. The final sample included 1448 participants (1229 men and 219 women). All participants reported on their current mental health, public stigma, self-stigma, and barriers to mental healthcare. Results: Overall, men and women reported similar levels of both structural and attitudinal barriers, with no significant differences detected. The highest scores for both men and women were observed in attitudinal barriers relating to self-stigma domains, which encapsulate internalised attitudes and beliefs about mental illness and treatment. Conclusions: Findings suggest that anti-stigma campaigns can be targeted simultaneously at both men and women within the Armed Forces. In particular, targeting self-stigma may be beneficial for health promotion campaigns

Oral Transmissibility of Prion Disease Is Enhanced by Binding to Soil Particles

Soil may serve as an environmental reservoir for prion infectivity and contribute to the horizontal transmission of prion diseases (transmissible spongiform encephalopathies [TSEs]) of sheep, deer, and elk. TSE infectivity can persist in soil for years, and we previously demonstrated that the disease-associated form of the prion protein binds to soil particles and prions adsorbed to the common soil mineral montmorillonite (Mte) retain infectivity following intracerebral inoculation. Here, we assess the oral infectivity of Mte- and soil-bound prions. We establish that prions bound to Mte are orally bioavailable, and that, unexpectedly, binding to Mte significantly enhances disease penetrance and reduces the incubation period relative to unbound agent. Cox proportional hazards modeling revealed that across the doses of TSE agent tested, Mte increased the effective infectious titer by a factor of 680 relative to unbound agent. Oral exposure to Mte-associated prions led to TSE development in experimental animals even at doses too low to produce clinical symptoms in the absence of the mineral. We tested the oral infectivity of prions bound to three whole soils differing in texture, mineralogy, and organic carbon content and found soil-bound prions to be orally infectious. Two of the three soils increased oral transmission of disease, and the infectivity of agent bound to the third organic carbon-rich soil was equivalent to that of unbound agent. Enhanced transmissibility of soil-bound prions may explain the environmental spread of some TSEs despite the presumably low levels shed into the environment. Association of prions with inorganic microparticles represents a novel means by which their oral transmission is enhanced relative to unbound agent