1,968 research outputs found
Mangarara Formation: exhumed remnants of a middle Miocene, temperate carbonate, submarine channel-fan system on the eastern margin of Taranaki Basin, New Zealand
The middle Miocene Mangarara Formation is a thin (1–60 m), laterally discontinuous unit of moderately to highly calcareous (40–90%) facies of sandy to pure limestone, bioclastic sandstone, and conglomerate that crops out in a few valleys in North Taranaki across the transition from King Country Basin into offshore Taranaki Basin. The unit occurs within hemipelagic (slope) mudstone of Manganui Formation, is stratigraphically associated with redeposited sandstone of Moki Formation, and is overlain by redeposited volcaniclastic sandstone of Mohakatino Formation. The calcareous facies of the Mangarara Formation are interpreted to be mainly mass-emplaced deposits having channelised and sheet-like geometries, sedimentary structures supportive of redeposition, mixed environment fossil associations, and stratigraphic enclosure within bathyal mudrocks and flysch. The carbonate component of the deposits consists mainly of bivalves, larger benthic foraminifers (especially Amphistegina), coralline red algae including rhodoliths (Lithothamnion and Mesophyllum), and bryozoans, a warm-temperate, shallow marine skeletal association. While sediment derivation was partly from an eastern contemporary shelf, the bulk of the skeletal carbonate is inferred to have been sourced from shoal carbonate factories around and upon isolated basement highs (Patea-Tongaporutu High) to the south. The Mangarara sediments were redeposited within slope gullies and broad open submarine channels and lobes in the vicinity of the channel-lobe transition zone of a submarine fan system. Different phases of sediment transport and deposition (lateral-accretion and aggradation stages) are identified in the channel infilling. Dual fan systems likely co-existed, one dominating and predominantly siliciclastic in nature (Moki Formation), and the other infrequent and involving the temperate calcareous deposits of Mangarara Formation. The Mangarara Formation is an outcrop analogue for middle Miocene-age carbonate slope-fan deposits elsewhere in subsurface Taranaki Basin, New Zealand
Early growth response 2 (EGR2) is a novel regulator of the senescence programme.
Senescence, a state of stable growth arrest, plays an important role in ageing and age-related diseases in vivo. Although the INK4/ARF locus is known to be essential for senescence programmes, the key regulators driving p16 and ARF transcription remain largely underexplored. Using siRNA screening for modulators of the p16/pRB and ARF/p53/p21 pathways in deeply senescent human mammary epithelial cells (DS HMECs) and fibroblasts (DS HMFs), we identified EGR2 as a novel regulator of senescence. EGR2 expression is up-regulated during senescence, and its ablation by siRNA in DS HMECs and HMFs transiently reverses the senescent phenotype. We demonstrate that EGR2 activates the ARF and p16 promoters and directly binds to both the ARF and p16 promoters. Loss of EGR2 down-regulates p16 levels and increases the pool of p16- p21- 'reversed' cells in the population. Moreover, EGR2 overexpression is sufficient to induce senescence. Our data suggest that EGR2 is a direct transcriptional activator of the p16/pRB and ARF/p53/p21 pathways in senescence and a novel marker of senescence
Bi-local Construction of Sp(2N)/dS Higher Spin Correspondence
We derive a collective field theory of the singlet sector of the Sp(2N) sigma
model. Interestingly the hamiltonian for the bilocal collective field is the
same as that of the O(N) model. However, the large-N saddle points of the two
models differ by a sign. This leads to a fluctuation hamiltonian with a
negative quadratic term and alternating signs in the nonlinear terms which
correctly reproduces the correlation functions of the singlet sector. Assuming
the validity of the connection between O(N) collective fields and higher spin
fields in AdS, we argue that a natural interpretation of this theory is by a
double analytic continuation, leading to the dS/CFT correspondence proposed by
Anninos, Hartman and Strominger. The bi-local construction gives a map into the
bulk of de Sitter space-time. Its geometric pseudospin-representation provides
a framework for quantization and definition of the Hilbert space. We argue that
this is consistent with finite N grassmanian constraints, establishing the
bi-local representation as a nonperturbative framework for quantization of
Higher Spin Gravity in de Sitter space.Comment: 1 figur
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An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo.
BACKGROUND: Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan. METHODS: Using Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture. RESULTS: We developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo. CONCLUSIONS: Our method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors
Regional movements of the tiger shark, Galeocerdo cuvier, off northeastern Brazil: inferences regarding shark attack hazard
An abnormally high shark attack rate verified off Recife could be related to migratory behavior of tiger sharks. This situation started after the construction of the Suape port to the south of Recife. A previous study suggested that attacking sharks could be following northward currents and that they were being attracted shoreward by approaching vessels. In this scenario, such northward movement pattern could imply a higher probability of sharks accessing the littoral area of Recife after leaving Suape. Pop-up satellite archival taus were deployed on five tiger sharks caught off Recife to assess their movement patterns off northeastern Brazil. All tags transmitted from northward latitudes after 7-74 days of freedom. The shorter, soak distance between deployment and pop-up locations ranged between 33-209 km and implied minimum average speeds of 0.02-0.98 km.h(-1). Both pop-up locations and depth data suggest that tiger shark movements were conducted mostly over the continental shelf. The smaller sharks moved to deeper waters within 24 hours after releasing, but they assumed a shallower (< 50 m) vertical distribution for most of the monitoring period. While presenting the first data on tiger shark movements in the South Atlantic, this study also adds new information for the reasoning of the high shark attack rate verified in this region,State Government of Pernambuco and Petrobras (Brazil); Fundacao para a Ciencia e Tecnologia (Portugal) [MCTES/FCT/SFRH/BD/37065/2007
Congestive Heart Failure Leads to Prolongation of the PR Interval and Atrioventricular Junction Enlargement and Ion Channel Remodelling in the Rabbit.
Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ
A comparison of the seasonal movements of tiger sharks and green turtles provides insight into their predator-prey relationship
During the reproductive season, sea turtles use a restricted area in the vicinity of their nesting beaches, making them vulnerable to predation. At Raine Island (Australia), the highest density green turtle Chelonia mydas rookery in the world, tiger sharks Galeocerdo cuvier have been observed to feed on green turtles, and it has been suggested that they may specialise on such air-breathing prey. However there is little information with which to examine this hypothesis. We compared the spatial and temporal components of movement behaviour of these two potentially interacting species in order to provide insight into the predator-prey relationship. Specifically, we tested the hypothesis that tiger shark movements are more concentrated at Raine Island during the green turtle nesting season than outside the turtle nesting season when turtles are not concentrated at Raine Island. Turtles showed area-restricted search behaviour around Raine Island for ~3–4 months during the nesting period (November–February). This was followed by direct movement (transit) to putative foraging grounds mostly in the Torres Straight where they switched to area-restricted search mode again, and remained resident for the remainder of the deployment (53–304 days). In contrast, tiger sharks displayed high spatial and temporal variation in movement behaviour which was not closely linked to the movement behaviour of green turtles or recognised turtle foraging grounds. On average, tiger sharks were concentrated around Raine Island throughout the year. While information on diet is required to determine whether tiger sharks are turtle specialists our results support the hypothesis that they target this predictable and plentiful prey during turtle nesting season, but they might not focus on this less predictable food source outside the nesting season
Quantification of atopy, lung function and airway hypersensitivity in adults
<p>Abstract</p> <p>Background</p> <p>Studies in children have shown that concentration of specific serum IgE (sIgE) and size of skin tests to inhalant allergens better predict wheezing and reduced lung function than the information on presence or absence of atopy. However, very few studies in adults have investigated the relationship of quantitative atopy with lung function and airway hyperresponsiveness (AHR).</p> <p>Objective</p> <p>To determine the association between lung function and AHR and quantitative atopy in a large sample of adults from the UK.</p> <p>Methods</p> <p>FEV<sub>1</sub> and FVC (% predicted) were measured using spirometry and airway responsiveness by methacholine challenge (5-breath dosimeter protocol) in 983 subjects (random sample of 800 parents of children enrolled in a population-based birth cohort enriched with 183 patients with physician-diagnosed asthma). Atopic status was assessed by skin prick tests (SPT) and measurement of sIgE (common inhalant allergens). We also measured indoor allergen exposure in subjects' homes.</p> <p>Results</p> <p>Spirometry was completed by 792 subjects and 626 underwent methacholine challenge, with 100 (16.0%) having AHR (dose-response slope>25). Using sIgE as a continuous variable in a multiple linear regression analysis, we found that increasing levels of sIgE to mite, cat and dog were significantly associated with lower FEV<sub>1</sub> (mite p = 0.001, cat p = 0.0001, dog p = 2.95 × 10<sup>-8</sup>). Similar findings were observed when using the size of wheal on skin testing as a continuous variable, with significantly poorer lung function with increasing skin test size (mite p = 8.23 × 10<sup>-8</sup>, cat p = 3.93 × 10<sup>-10</sup>, dog p = 3.03 × 10<sup>-15</sup>, grass p = 2.95 × 10<sup>-9</sup>). The association between quantitative atopy with lung function and AHR remained unchanged when we repeated the analyses amongst subjects defined as sensitised using standard definitions (sIgE>0.35 kUa/l, SPT-3 mm>negative control).</p> <p>Conclusions</p> <p>In the studied population, lung function decreased and AHR increased with increasing sIgE levels or SPT wheal diameter to inhalant allergens, suggesting that atopy may not be a dichotomous outcome influencing lung function and AHR.</p
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