Beyond the bipolar seesaw: toward a process understanding of interhemispheric coupling

The thermal bipolar ocean seesaw hypothesis was advanced by Stocker and Johnsen (2003) as the ‘simplest possible thermodynamic model’ to explain the time relationship between Dansgaard–Oeschger (DO) and Antarctic Isotope Maxima (AIM) events. In this review we combine palaeoclimate observations, theory and general circulation model experiments to advance from the conceptual model toward a process understanding of interhemispheric coupling and the forcing of AIM events. We present four main results: (1) Changes in Atlantic heat transport invoked by the thermal seesaw are partially compensated by opposing changes in heat transport by the global atmosphere and Pacific Ocean. This compensation is an integral part of interhemispheric coupling, with a major influence on the global pattern of climate anomalies. (2) We support the role of a heat reservoir in interhemispheric coupling but argue that its location is the global interior ocean to the north of the Antarctic Circumpolar Current (ACC), not the commonly assumed Southern Ocean. (3) Energy budget analysis indicates that the process driving Antarctic warming during AIM events is an increase in poleward atmospheric heat and moisture transport following sea ice retreat and surface warming over the Southern Ocean. (4) The Antarctic sea ice retreat is itself driven by eddy-heat fluxes across the ACC, amplified by sea-ice–albedo feedbacks. The lag of Antarctic warming after AMOC collapse reflects the time required for heat to accumulate in the ocean interior north of the ACC (predominantly the upper 1500 m), before it can be mixed across this dynamic barrier by eddies

Erosion protection benefits of stabilized SnF2 dentifrice versus an arginine–sodium monofluorophosphate dentifrice:results from in vitro and in situ clinical studies

OBJECTIVES: The aim of these investigations was to assess the ability of two fluoride dentifrices to protect against the initiation and progression of dental erosion using a predictive in vitro erosion cycling model and a human in situ erosion prevention clinical trial for verification of effectiveness. MATERIALS AND METHODS: A stabilized stannous fluoride (SnF(2)) dentifrice (0.454 % SnF(2) + 0.077 % sodium fluoride [NaF]; total F = 1450 ppm F) [dentifrice A] and a sodium monofluorophosphate [SMFP]/arginine dentifrice (1.1 % SMFP + 1.5 % arginine; total F = 1450 ppm F) [dentifrice B] were tested in a 5-day in vitro erosion cycling model and a 10-day randomized, controlled, double-blind, two-treatment, four-period crossover in situ clinical trial. In each study, human enamel specimens were exposed to repetitive product treatments using a standardized dilution of test products followed by erosive acid challenges in a systematic fashion. RESULTS: Both studies demonstrated statistically significant differences between the two products, with dentifrice A providing significantly better enamel protection in each study. In vitro, dentifrice A provided a 75.8 % benefit over dentifrice B (p < 0.05, ANOVA), while after 10 days in the in situ model, dentifrice A provided 93.9 % greater protection versus dentifrice B (p < 0.0001, general linear mixed model). CONCLUSION: These results support the superiority of stabilized SnF(2) dentifrices for protecting human teeth against the initiation and progression of dental erosion. CLINICAL RELEVANCE: Stabilized SnF(2) dentifrices may provide more significant benefits to consumers than conventional fluoride dentifrices

Acute WNT signalling activation perturbs differentiation within the adult stomach and rapidly leads to tumour formation

A role for WNT signalling in gastric carcinogenesis has been suggested due to two major observations. First, patients with germline mutations in adenomatous polyposis coli (APC) are susceptible to stomach polyps and second, in gastric cancer, WNT activation confers a poor prognosis. However, the functional significance of deregulated WNT signalling in gastric homoeostasis and cancer is still unclear. In this study we have addressed this by investigating the immediate effects of WNT signalling activation within the stomach epithelium. We have specifically activated the WNT signalling pathway within the mouse adult gastric epithelium via deletion of either glycogen synthase kinase 3 (GSK3) or APC or via expression of a constitutively active β-catenin protein. WNT pathway deregulation dramatically affects stomach homoeostasis at very short latencies. In the corpus, there is rapid loss of parietal cells with fundic gland polyp (FGP) formation and adenomatous change, which are similar to those observed in familial adenomatous polyposis. In the antrum, adenomas occur from 4 days post-WNT activation. Taken together, these data show a pivotal role for WNT signalling in gastric homoeostasis, FGP formation and adenomagenesis. Loss of the parietal cell population and corresponding FGP formation, an early event in gastric carcinogenesis, as well as antral adenoma formation are immediate effects of nuclear β-catenin translocation and WNT target gene expression. Furthermore, our inducible murine model will permit a better understanding of the molecular changes required to drive tumourigenesis in the stomach

Hysteresis and the dynamic phase transition in thin ferromagnetic films

Hysteresis and the non-equilibrium dynamic phase transition in thin magnetic films subject to an oscillatory external field have been studied by Monte Carlo simulation. The model under investigation is a classical Heisenberg spin system with a bilinear exchange anisotropy in a planar thin film geometry with competing surface fields. The film exhibits a non-equilibrium phase transition between dynamically ordered and dynamically disordered phases characterized by a critical temperature Tcd, whose location of is determined by the amplitude H0 and frequency w of the applied oscillatory field. In the presence of competing surface fields the critical temperature of the ferromagnetic-paramagnetic transition for the film is suppressed from the bulk system value, Tc, to the interface localization-delocalization temperature Tci. The simulations show that in general Tcd < Tci for the model film. The profile of the time-dependent layer magnetization across the film shows that the dynamically ordered and dynamically disordered phases coexist within the film for T < Tcd. In the presence of competing surface fields, the dynamically ordered phase is localized at one surface of the film.Comment: PDF file, 21 pages including 8 figure pages; added references,typos added; to be published in PR

The effects of aging and maternal protein restriction during lactation on thymic involution and peripheral immunosenescence in adult mice.

Environmental factors such as nutrition during early life can influence long-term health, a concept termed developmental programming. Initial research was focused towards the effects on metabolic health but more recent studies have demonstrated effects on parameters such as lifespan and immunity. In this study we report that maternal protein restriction during lactation in mice, that is known to prolong lifespan, slows aging of the central and peripheral immune systems. Offspring of dams fed a postnatal low-protein (PLP) diet during lactation had a significant increase in thymic cellularity and T cell numbers across their lifespan compared to controls, and a less marked age-associated decrease in thymocyte cluster of differentiation (CD) 3 expression. PLP animals also demonstrated increased relative splenic cellularity, increased naïve: memory CD4+ and CD8+ T cell ratios, increased staining and density of germinal centres, and decreased gene expression of p16 in the spleen, a robust biomarker of aging. A slower rate of splenic aging in PLP animals would be expected to result in decreased susceptibility to infection and neoplasia. In conclusion nutritionally-induced slow postnatal growth leads to delayed aging of the adaptive immune system, which may contribute towards the extended lifespan observed in these animals.This work was supported by the BBSRC and the MRC. SEO is funded by the University of Cambridge MRC Metabolic Diseases Unit (MRC_MC_UU_12012/4).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Impact Journals

Near-IR sensitization of wide band gap oxide semiconductor by axially anchored Si-naphthalocyanines

Near-IR dye sensitized solar cells are very interesting due to their potential applications in panchromatic cells, semi-transparent windows and in tandem cells. In this work we show the utilization of axially anchored Si-naphthalocyanine dye in the spectral sensitization of TiO2 nanostructured photoelectrodes. We report the first successful evaluation of a naphthalocyanine in the production of sensitized photocurrent with maximum incident photon to current efficiency (IPCE) at λ 790 n

Electric-field-induced coherent coupling of the exciton states in a single quantum dot

The signature of coherent coupling between two quantum states is an anticrossing in their energies as one is swept through the other. In single semiconductor quantum dots containing an electron-hole pair the eigenstates form a two-level system that can be used to demonstrate quantum effects in the solid state, but in all previous work these states were independent. Here we describe a technique to control the energetic splitting of these states using a vertical electric field, facilitating the observation of coherent coupling between them. Near the minimum splitting the eigenstates rotate in the plane of the sample, being orientated at 45{\deg} when the splitting is smallest. Using this system we show direct control over the exciton states in one quantum dot, leading to the generation of entangled photon pairs

Canonical Wnt signals combined with suppressed TGFβ/BMP pathways promote renewal of the native human colonic epithelium

Background: A defining characteristic of the human intestinal epithelium is that it is the most rapidly renewing tissue in the body. However, the processes underlying tissue renewal and the mechanisms that govern their coordination have proved difficult to study in the human gut. Objective: To investigate the regulation of stem cell-driven tissue renewal by canonical Wnt and TGFβ/bone morphogenetic protein (BMP) pathways in the native human colonic epithelium. Design: Intact human colonic crypts were isolated from mucosal tissue samples and placed into 3D culture conditions optimised for steady-state tissue renewal. High affinity mRNA in situ hybridisation and immunohistochemistry were complemented by functional genomic and bioimaging techniques. The effects of signalling pathway modulators on the status of intestinal stem cell biology, crypt cell proliferation, migration, differentiation and shedding were determined. Results: Native human colonic crypts exhibited distinct activation profiles for canonical Wnt, TGFβ and BMP pathways. A population of intestinal LGR5/OLFM4-positive stem/progenitor cells were interspersed between goblet-like cells within the crypt-base. Exogenous and crypt cell-autonomous canonical Wnt signals supported homeostatic intestinal stem/progenitor cell proliferation and were antagonised by TGFβ or BMP pathway activation. Reduced Wnt stimulation impeded crypt cell proliferation, but crypt cell migration and shedding from the crypt surface were unaffected and resulted in diminished crypts. Conclusions: Steady-state tissue renewal in the native human colonic epithelium is dependent on canonical Wnt signals combined with suppressed TGFβ/BMP pathways. Stem/progenitor cell proliferation is uncoupled from crypt cell migration and shedding, and is required to constantly replenish the crypt cell population

Prenatal hypoxia induces increased cardiac contractility on a background of decreased capillary density.

Background: Chronic hypoxia in utero (CHU) is one of the most common insults to fetal development and may be associated with poor cardiac recovery from ischaemia-reperfusion injury,yet the effects on normal cardiac mechanical performance are poorly understood. Methods: Pregnant female wistar rats were exposed to hypoxia (12% oxygen, balance nitrogen)for days 10–20 of pregnancy. Pups were born into normal room air and weaned normally. At 10 weeks of age, hearts were excised under anaesthesia and underwent retrograde 'Langendorff' perfusion. Mechanical performance was measured at constant filling pressure (100 cm H2O) with intraventricular balloon. Left ventricular free wall was dissected away and capillary density estimated following alkaline phosphatase staining. Expression of SERCA2a and Nitric Oxide Synthases (NOS) proteins were estimated by immunoblotting. Results: CHU significantly increased body mass (P < 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P < 0.01) and up to 200 μl (P < 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P < 0.05).Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P <0.05) and endocardium (11%; P < 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P < 0.001) in cardiac tissue following chronic hypoxia in utero. Conclusion: These data offer potential mechanisms for poor recovery following ischaemia, including decreased coronary flow reserve and impaired angiogenesis with subsequent detrimental effects of post-natal cardiac performance