The thermal history of the Western Irish onshore

We present here a low-temperature thermochronological study that combines the apatite fission-track and (U + Th)/He dating methods with a pseudo-vertical sampling approach to generate continuous and well-constrained temperature–time histories from the onshore Irish Atlantic margin. The apatite fission-track and (U + Th)/He ages range from the Late Jurassic to Early Cretaceous and the mean track lengths are relatively short. Thermal histories derived from inverse modelling show that following post-orogenic exhumation the sample profiles cooled to c. 75 °C. A rapid cooling event to surface temperatures occurred during the Late Jurassic to Early Cretaceous and was diachronous from north to south. It was most probably caused by c. 2.5 km of rift-shoulder related exhumation and can be temporally linked to the main stage of Mesozoic rifting in the offshore basins. A slow phase of reheating during the Late Cretaceous and Early Cenozoic is attributed to the deposition of a thick sedimentary sequence that resulted in c. 1.5 km of burial. Our data imply a final pulse of exhumation in Neogene times, probably related to compression of the margin. However, it is possible that an Early Cenozoic cooling event, compatible with our data but not seen in our inverse models, accounts for part of the Cenozoic exhumation

Measuring plume-related exhumation of the British Isles in Early Cenozoic times

Mantle plumes have been proposed to exert a first-order control on the morphology of Earth's surface. However, there is little consensus on the lifespan of the convectively supported topography. Here, we focus on the Cenozoic uplift and exhumation history of the British Isles. While uplift in the absence of major regional tectonic activity has long been documented, the causative mechanism is highly controversial, and direct exhumation estimates are hindered by the near-complete absence of onshore post-Cretaceous sediments (outside Northern Ireland) and the truncated stratigraphic record of many offshore basins. Two main hypotheses have been developed by previous studies: epeirogenic exhumation driven by the proto-Iceland plume, or multiple phases of Cenozoic compression driven by far-field stresses. Here, we present a new thermochronological dataset comprising 43 apatite fission track (AFT) and 102 (U–Th–Sm)/He (AHe) dates from the onshore British Isles. Inverse modelling of vertical sample profiles allows us to define well-constrained regional cooling histories. Crucially, during the Paleocene, the thermal history models show that a rapid exhumation pulse (1–2.5 km) occurred, focused on the Irish Sea. Exhumation is greatest in the north of the Irish Sea region, and decreases in intensity to the south and west. The spatial pattern of Paleocene exhumation is in agreement with the extent of magmatic underplating inferred from geophysical studies, and the timing of uplift and exhumation is synchronous with emplacement of the plume-related British and Irish Paleogene Igneous Province (BIPIP). Prior to the Paleocene exhumation pulse, the Mesozoic onshore exhumation pulse is mainly linked to the uplift and erosion of the hinterland during the complex and long-lived rifting history of the neighbouring offshore basins. The extent of Neogene exhumation is difficult to constrain due to the poor sensitivity of the AHe and AFT systems at low temperatures. We conclude that the Cenozoic topographic evolution of the British Isles is the result of plume-driven uplift and exhumation, with inversion under compressive stress playing a secondary role

The Ocean – Continent Transition Zones Along the Appalachian – Caledonian Margin of Laurentia: Examples of Large-Scale Hyperextension During the Opening of the Iapetus Ocean

A combination of deep seismic imaging and drilling has demonstrated that the ocean-continent transition (OCT) of present-day, magma-poor, rifted continental margins is a zone of hyperextension characterized by extreme thinning of the continental crust that exhumed the lowermost crust and/or serpentinized continental mantle onto the seafloor. The OCT on present-day margins is difficult to sample, and so much of our knowledge on the detailed nature of OCT sequences comes from obducted, magma-poor OCT ophiolites such as those preserved in the upper portions of the Alpine fold-and-thrust belt. Allochthonous, lens-shaped bodies of ultramafic rock are common in many other ancient orogenic belts, such as the Caledonian – Appalachian orogen, yet their origin and tectonic significance remains uncertain. We summarize the occurrences of potential ancient OCTs within this orogen, commencing with Laurentian margin sequences where an OCT has previously been inferred (the Dalradian Supergroup of Scotland and Ireland and the Birchy Complex of Newfoundland). We then speculate on the origin of isolated occurrences of Alpine-type peridotite within Laurentian margin sequences in Quebec – Vermont and Virginia – North Carolina, focusing on rift-related units of Late Neoproterozoic age (so as to eliminate a Taconic ophiolite origin). A combination of poor exposure and pervasive Taconic deformation means that origin and emplacement of many ultramafic bodies in the Appalachians will remain uncertain. Nevertheless, the common occurrence of OCT-like rocks along the whole length of the Appalachian – Caledonian margin of Laurentia suggests that the opening of the Iapetus Ocean may have been accompanied by hyperextension and the formation of magma-poor margins along many segments.SOMMAIREDes travaux d’imagerie sismique et des forages profonds ont montré que la transition océan-continent (OCT) de marges continentales de divergence pauvre en magma exposée de nos jours, correspond à une zone d’hyper-étirement tectonique caractérisée par un amincissement extrême de la croûte continentale, qui a exhumé sur le fond marin, jusqu’à la tranche la plus profonde de la croûte continentale, voire du manteau continental serpentinisé.  Parce qu’on peut difficilement échantillonner l’OCT sur les marges actuelles, une grande partie de notre compréhension des détails de la nature de l’OCT provient d’ophiolites pauvres en magma d’une OCT obduite, comme celles préservées dans les portions supérieures de la bande plissée alpine.  Des masses lenticulaires de roches ultramafiques allochtones sont communes dans de nombreuses autres bandes orogéniques anciennes, comme l’orogène Calédonienne-Appalaches, mais leur origine et signification tectonique reste incertaine.  Nous présentons un sommaire des occurrences d’OCT potentielles anciennes de cet orogène, en commençant par des séquences de la marge laurentienne, où la présence d’OCT a déjà été déduites (le Supergroupe Dalradien d’Écosse et d'Irlande, et le complexe de Birchy de Terre-Neuve).  Nous spéculons ensuite sur l'origine de cas isolés de péridotite de type alpin dans des séquences de marge des Laurentides du Québec-Vermont et de la Virginie-Caroline du Nord, en nous concentrant sur les unités de rift d'âge néoprotérozoïque tardif (pour éviter les ophiolites du Taconique).  La conjonction d’affleurements de piètre qualité et de la déformation taconique omniprésente, signifie que l'origine et la mise en place de nombreuses masses ultramafiques dans les Appalaches demeureront incertaines.  Néanmoins, la présence fréquente de roches de type OCT tout le long de la marge Calédonnienne-Appalaches de Laurentia suggère que l'ouverture de l'océan Iapetus peut avoir été accompagnée d’hyper-étirement et de la formation de marges pauvres en magma le long de nombreux segments

Hyperon-Nucleon Final State Interaction in Kaon Photoproduction of the Deuteron

Final state hyperon-nucleon interaction in strangeness photoproduction of the deuteron is investigated making use of the covariant reaction formalism and the P-matrix approach to the YN system. Remarkably simple analytical expression for the amplitude is obtained. Pronounced effects due to final state interaction are predicted including the manifestation of the 2.13 GeV resonance.Comment: LaTeX, 13 page

Development and validation of the DIabetes Severity SCOre (DISSCO) in 139 626 individuals with type 2 diabetes: a retrospective cohort study

OBJECTIVE: Clinically applicable diabetes severity measures are lacking, with no previous studies comparing their predictive value with glycated hemoglobin (HbA1c). We developed and validated a type 2 diabetes severity score (the DIabetes Severity SCOre, DISSCO) and evaluated its association with risks of hospitalization and mortality, assessing its additional risk information to sociodemographic factors and HbA1c. RESEARCH DESIGN AND METHODS: We used UK primary and secondary care data for 139 626 individuals with type 2 diabetes between 2007 and 2017, aged ≥35 years, and registered in general practices in England. The study cohort was randomly divided into a training cohort (n=111 748, 80%) to develop the severity tool and a validation cohort (n=27 878). We developed baseline and longitudinal severity scores using 34 diabetes-related domains. Cox regression models (adjusted for age, gender, ethnicity, deprivation, and HbA1c) were used for primary (all-cause mortality) and secondary (hospitalization due to any cause, diabetes, hypoglycemia, or cardiovascular disease or procedures) outcomes. Likelihood ratio (LR) tests were fitted to assess the significance of adding DISSCO to the sociodemographics and HbA1c models. RESULTS: A total of 139 626 patients registered in 400 general practices, aged 63±12 years were included, 45% of whom were women, 83% were White, and 18% were from deprived areas. The mean baseline severity score was 1.3±2.0. Overall, 27 362 (20%) people died and 99 951 (72%) had ≥1 hospitalization. In the training cohort, a one-unit increase in baseline DISSCO was associated with higher hazard of mortality (HR: 1.14, 95% CI 1.13 to 1.15, area under the receiver operating characteristics curve (AUROC)=0.76) and cardiovascular hospitalization (HR: 1.45, 95% CI 1.43 to 1.46, AUROC=0.73). The LR tests showed that adding DISSCO to sociodemographic variables significantly improved the predictive value of survival models, outperforming the added value of HbA1c for all outcomes. Findings were consistent in the validation cohort. CONCLUSIONS: Higher levels of DISSCO are associated with higher risks for hospital admissions and mortality. The new severity score had higher predictive value than the proxy used in clinical practice, HbA1c. This reproducible algorithm can help practitioners stratify clinical care of patients with type 2 diabetes

The anti-apoptotic activity of XIAP is retained upon mutation of both the caspase 3– and caspase 9–interacting sites

The X-linked mammalian inhibitor of apoptosis protein (XIAP) has been shown to bind several partners. These partners include caspase 3, caspase 9, DIABLO/Smac, HtrA2/Omi, TAB1, the bone morphogenetic protein receptor, and a presumptive E2 ubiquitin-conjugating enzyme. In addition, we show here that XIAP can bind to itself. To determine which of these interactions are required for it to inhibit apoptosis, we generated point mutant XIAP proteins and correlated their ability to bind other proteins with their ability to inhibit apoptosis. ∂RING point mutants of XIAP were as competent as their full-length counterparts in inhibiting apoptosis, although impaired in their ability to oligomerize with full-length XIAP. Triple point mutants, unable to bind caspase 9, caspase 3, and DIABLO/HtrA2/Omi, were completely ineffectual in inhibiting apoptosis. However, point mutants that had lost the ability to inhibit caspase 9 and caspase 3 but retained the ability to inhibit DIABLO were still able to inhibit apoptosis, demonstrating that IAP antagonism is required for apoptosis to proceed following UV irradiation

Acute effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity and cardiorespiratory responses in dogs

Funding: Silvia V. Conde declares that Galvani Bioelectronics provided funds to support their work associated with Type 2 diabetic project.New Findings: What is the central question of this study? What are the effects of insulin and insulin-induced hypoglycaemia on carotid body chemoreceptor activity in vivo and how do carotid body chemoreceptor stimulation-mediated cardiorespiratory responses in beagle dogs compare during euglycaemia and insulin-induced hypoglycaemia? What is the main finding and its importance? Intracarotid insulin administration leads to sustained increase in carotid body chemoreceptor activity and respiratory response with significant cardiovascular effects. Insulin-induced hypoglycaemia exacerbated NaCN-mediated carotid body chemoreceptor activity and respiratory response with enhanced cardiovascular reflex response. These findings suggest that insulin-induced hypoglycaemia augments the carotid body chemoreceptors to initiate the adaptive counter-regulatory responses to restore the normoglycaemic condition. Abstract: The carotid body chemoreceptors (CBC) play an important role in the adaptive counter-regulatory response to hypoglycaemia by evoking the CBC-mediated sympathetic neuronal system to restore normoglycaemia. Ex vivo studies have shown varied responses of insulin-induced hypoglycaemia on CBC function, and several in vivo studies have indirectly established the role of CBCs in restoring normoglycaemia in both animals and humans. However, a direct effect of insulin and/or insulin-induced hypoglycaemia on CBC activity is not established in animal models. Therefore, the aim of this study was to evaluate in vivo effects of insulin and insulin-induced hypoglycaemia on CBC activity and cardiorespiration in a preclinical large animal model. The carotid sinus nerve (CSN) activity and cardiorespiratory responses to sodium cyanide (NaCN; 25 µg/kg) were compared before (euglycaemic) and after (hypoglycaemic) intracarotid administration of insulin (12.5–100 µU/dogs) in beagle dogs. Insulin administration increased CSN activity and minute ventilation ((Formula presented.) E) with significant (P < 0.0001) effects on heart rate and blood pressure. Insulin-mediated effects on CSN and cardiorespiration were sustained and the change in (Formula presented.) E was driven by tidal volume only. Insulin significantly (P < 0.0001) lowered blood glucose level. NaCN-mediated CSN activity and (Formula presented.) E were significantly (P < 0.0001) augmented during insulin-induced hypoglycaemia. The augmented (Formula presented.) E was primarily driven by respiratory frequency and partially by tidal volume. The cardiovascular reflex response mediated through CBC stimulation was significantly (P < 0.0001) exacerbated during insulin-induced hypoglycaemia. Collectively, these results demonstrate direct effects of insulin and insulin-induced hypoglycaemia on CBC chemosensitivity to potentiate CBC-mediated neuroregulatory pathways to initiate adaptive neuroendocrine and cardiorespiratory counter-regulatory responses to restore normoglycaemia.publishersversionepub_ahead_of_prin

The Importance of Eurekan Mountains on Cenozoic Sediment Routing on the Western Barents She

The importance of topography generated by Eocene Eurekan deformation as a sediment source for sandstones deposited on the western Barents Shelf margin is evaluated through a sediment provenance study conducted on wellbore materials retrieved from Spitsbergen and from the Vestbakken Volcanic Province and the Sørvestsnaget Basin in the southwest Barents Sea. A variety of complementary techniques record a provenance change across the Paleocene-Eocene boundary in wellbore BH 10-2008, which samples Paleogene strata of the Central Tertiary Basin in Spitsbergen. Sandstones containing K-feldspar with radiogenic Pb isotopic compositions, chrome spinel in the heavy mineral assemblage, and detrital zircons and rutiles with prominent Palaeoproterozoic and Late Palaeozoic—Early Mesozoic U-Pb age populations are up-section replaced by sandstone containing albitic plagioclase feldspar, metasedimentary schist rock fragments, a heavy mineral assemblage with abundant chloritoid, metamorphic apatite with low REE contents, metapelitic rutile with Silurian U-Pb ages and zircons with predominantly Archaean and Palaeoproterozoic U-Pb age populations. Our results clearly demonstrate the well-known regional change in source area from an exposed Barents Shelf terrain east of the Central Tertiary Basin during the Paleocene to the emerging Eurekan mountains west and north of the Central Tertiary Basin during the Eocene. Eocene sandstones deposited in the marginal basins of the southwestern Barents Shelf, which were sampled in wellbores 7316/5-1 and 7216/11-1S, contain elements of both the Eurekan and the eastern Barents Shelf provenance signatures. The mixing of the two sand types and delivery to the southwest margin of the Barents Shelf is consistent with a fill and spill model for the Central Teritary Basin, with transport of Eurekan-derived sediment east then south hundreds of kilometres across the Shelf