Shoot dieback in clipped young Golden Leyland (Cupressocyparis leylandii) trees - a physiological mechanism?

Shoot dieback is a problem in frequently trimmed Leyland hedges and is increasingly affecting gardeners’ choice of hedge trees, having a negative effect on a conifer nursery industry. Some damage can be attributed to the feeding by aphids, but it is unclear if there are also underlying physiological causes. In this study, we tested the hypothesis that shoot-clipping of conifer trees during adverse growing conditions (i.e. high air temperature and low soil moisture) could be leading to shoot ‘dieback’. Three-year-old Golden Leyland Cypress (x Cupressocyparis leylandii ‘Excalibur Gold’) plants were subjected to either a well-watered or droughted irrigation regime and placed in either a ‘hot’ (average day temperature = 40°C) or a ‘cool’ (average day temperature = 27°C) glasshouse compartment. Half of the plants from each glasshouse were clipped on Day 14 and again on Day 50. Measurements of soil moisture content (SMC), net CO2 assimilation rate (A), stomatal conductance (gs), branchlet xylem water potential (XWP), plant height and foliage colour were made. Within the clipped and unclipped treatments of both glasshouse compartments, plants from the droughted regime had significantly lower values for A, gs and XWP than those from the well-watered regime. However, there was no difference in these parameters between the hot and cool glasshouse compartments. The trends seen for A, gs and XWP of all treatments generally mirrored changes in SMC indicating a direct effect of water supply on these parameters. By the end of the experiment the overall foliage colour of plants from the hot glasshouse was darker than that of plants from the cool glasshouse and the overall foliage colour was also darker following shoot clipping. In general, shoot clipping led to increases in A, gs XWP and SMC. This may be due to the reduction in total leaf area leading to a greater supply of water for the remaining leaves. No shoot ‘dieback’ was observed in any treatment in response to drought stress or shoot-clipping.

Zinc-histidine complex protects cultured cortical neurons against oxidative stress-induced damage

The levels of zinc in the brain are directly affected by dietary zinc and deficiency has been associated with alcohol withdrawal seizures, excitotoxicity, impaired learning and memory and an accelerated rate of dysfunction in aged brain. Although zinc is essential for a healthy nervous system, high concentrations of zinc are neurotoxic, thus it is important to identify the most effective forms of zinc for treatment of conditions of the central nervous system. Accumulating evidence suggests that zinc-histidine complex (Zn(HiS)(2)) has greater biological potency and enhanced bioavailability compared with other zinc salts and also has antioxidant potential. Therefore, in this study we investigated the ability of zinc-histidine to protect cultured cortical neurons against hydrogen peroxide-induced damage. Pre-treating neurons for 18h with subtoxic concentrations of zinc-histidine (5-25 muM) improved neuronal viability and strongly inhibited hydrogen peroxide-induced (75 muM, 30 min) cell damage as assessed by MTT turnover and morphological analysis 24 It later. Low concentrations of zinc-histidine were more neuroprotective than zinc chloride. There was evidence of an anti-apoptotic mechanism of action as zinc-histidine inhibited hydrogen peroxide-induced caspase-3 activation and c-jun-N-terminal kinase phosphorylation. In summary, zinc supplementation with zinc-histidine protects cultured neurons against oxidative insults and inhibits apoptosis which suggests that zinc-histidine may be beneficial in the treatment of diseases of the CNS associated with zinc deficiency. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Inhibition of cellular proliferation by the genistein metabolite 5,7,3',4'-tetrahydroxyisoflavone is mediated by DNA damage and activation of the ATR signalling pathway

The cellular actions of genistein, and its in vivo metabolites, are believed to mediate the decreased risk of breast cancer associated with high soy consumption. The genistein metabolite, 5,7,3',4'-tetrahydroxyisoflavone (THIF), induced G2-M cell cycle arrest in T47D tumorigenic breast epithelial cells via a mechanism involving the activation of ataxia telangiectasia and Rad3-related kinase (ATR) via its phosphorylation at Ser(428). This activation of ATR appeared to result from THIF-induced increases in intracellular oxidative stress, a depletion of cellular GSH and an increase in DNA strand breakage. THIF treatment also led to an inhibition of cdc2, which was accompanied by the phosphorylation of both p53 (Ser(15)) and Chk1 (Ser(296)) and the de-activation of cdc25C phosphatase. We suggest the anti-proliferative actions of THIF may be mediated by initial oxidative DNA damage, activation of ATR and downstream regulation of the p53 and Chk1 pathways leading to cell cycle arrest in G2-M. This may represent one mechanism by which genistein exerts its cellular activity in vivo. (c) 2007 Elsevier Inc. All rights reserved.

Role of oxygen radicals in DNA damage and cancer incidence

The development of cancer in humans and animals is a multistep process. The complex series of cellular and molecular changes participating in cancer development are mediated by a diversity of endogenous and exogenous stimuli. One type of endogenous damage is that arising from intermediates of oxygen (dioxygen) reduction - oxygen-free radicals (OFR), which attacks not only the bases but also the deoxyribosyl backbone of DNA. Thanks to improvements in analytical techniques, a major achievement in the understanding of carcinogenesis in the past two decades has been the identification and quantification of various adducts of OFR with DNA. OFR are also known to attack other cellular components such as lipids, leaving behind reactive species that in turn can couple to DNA bases. Endogenous DNA lesions are genotoxic and induce mutations. The most extensively studied lesion is the formation of 8-OH-dG. This lesion is important because it is relatively easily formed and is mutagenic and therefore is a potential biomarker of carcinogenesis. Mutations that may arise from formation of 8-OH-dG involve GC. TA transversions. In view of these findings, OFR are considered as an important class of carcinogens. The effect of OFR is balanced by the antioxidant action of non-enzymatic antioxidants as well as antioxidant enzymes. Non-enzymatic antioxidants involve vitamin C, vitamin E, carotenoids (CAR), selenium and others. However, under certain conditions, some antioxidants can also exhibit a pro-oxidant mechanism of action. For example, beta-carotene at high concentration and with increased partial pressure of dioxygen is known to behave as a pro-oxidant. Some concerns have also been raised over the potentially deleterious transition metal ion-mediated (iron, copper) pro-oxidant effect of vitamin C. Clinical studies mapping the effect of preventive antioxidants have shown surprisingly little or no effect on cancer incidence. The epidemiological trials together with in vitro experiments suggest that the optimal approach is to reduce endogenous and exogenous sources of oxidative stress, rather than increase intake of anti-oxidants. In this review, we highlight some major achievements in the study of DNA damage caused by OFR and the role in carcinogenesis played by oxidatively damaged DNA. The protective effect of antioxidants against free radicals is also discussed.

Adult skeletal muscle stem cell migration is mediated by a blebbing/amoeboid mechanism

Adult skeletal muscle possesses a resident stem cell population called satellite cells which are responsible for tissue repair following damage. Satellite cell migration is crucial in promoting rapid tissue regeneration but is a poorly understood process. Furthermore, the mechanisms facilitating satellite cell movement have yet to be elucidated. Here the process of satellite cell migration has been investigated revealing that they undergo two distinct phases of movement; firstly under the basal lamina and then rapidly increasing their velocity when on the myofibre surface. Most significantly we show that satellite cells move using a highly dynamic blebbing based mechanism and not via lamellopodia mediated propulsion. We show that nitric oxide and non-canonical Wnt signalling pathways are necessary for regulating the formation of blebs and the migration of satellite cells. In summary, we propose that the formation of blebs and their necessity for satellite cell migration has significant implications in the future development of therapeutic regimes aimed at promoting skeletal muscle regeneration.

Language in calculation: A core mechanism?

Although there is evidence that exact calculation recruits left hemisphere perisylvian language systems, recent work has shown that exact calculation can be retained despite severe damage to these networks. In this study, we sought to identify a “core” network for calculation and hence to determine the extent to which left hemisphere language areas are part of this network. We examined performance on addition and subtraction problems in two modalities: one using conventional two-digit problems that can be easily encoded into language; the other using novel shape representations. With regard to numerical problems, our results revealed increased left fronto-temporal activity in addition, and increased parietal activity in subtraction, potentially reflecting retrieval of linguistically encoded information during addition. The shape problems elicited activations of occipital, parietal and dorsal temporal regions, reflecting visual reasoning processes. A core activation common to both calculation types involved the superior parietal lobule bilaterally, right temporal sub-gyral area, and left lateralized activations in inferior parietal (BA 40), frontal (BA 6/8/32) and occipital (BA 18) regions. The large bilateral parietal activation could be attributed to visuo-spatial processing in calculation. The inferior parietal region, and particularly the left angular gyrus, was part of the core calculation network. However, given its activation in both shape and number tasks, its role is unlikely to reflect linguistic processing per se. A possibility is that it serves to integrate right hemisphere visuo-spatial and left hemisphere linguistic and executive processing in calculation.

Characterising loss and damage from climate change

Policy-makers are creating mechanisms to help developing countries cope with loss and damage from climate change, but the negotiations are largely neglecting scientific questions about what the impacts of climate change actually are. Mitigation efforts have failed to prevent the continued increase of anthropogenic greenhouse gas (GHG) emissions. Adaptation is now unlikely to be sufficient to prevent negative impacts from current and future climate change1. In this context, vulnerable nations argue that existing frameworks to promote mitigation and adaptation are inadequate, and have called for a third international mechanism to deal with residual climate change impacts, or “loss and damage”2. In 2013, the United Nations Framework Convention on Climate Change (UNFCCC) responded to these calls and established the Warsaw International Mechanism (WIM) to address loss and damage from the impacts of climate change in developing countries3. An interim Executive Committee of party representatives has been set up, and is currently drafting a two-year workplan comprising meetings, reports, and expert groups; and aiming to enhance knowledge and understanding of loss and damage, strengthen dialogue among stakeholders, and promote enhanced action and support. Issues identified as priorities for the WIM thus far include: how to deal with non-economic losses, such as loss of life, livelihood, and cultural heritage; and linkages between loss and damage and patterns of migration and displacement2. In all this, one fundamental issue still demands our attention: which losses and damages are relevant to the WIM? What counts as loss and damage from climate change?

Implications of event attribution for loss and damage policy

The United Nations Framework Convention on Climate Change (UNFCCC) has established the Warsaw International Mechanism (WIM) to deal with loss and damage associated with climate change impacts, including extreme events, in developing countries. It is not yet known whether events will need to be attributed to anthropogenic climate change to be considered under the WIM. Attribution is possible for some extreme events- a climate model assessment can estimate how greenhouse gas emissions have affected the likelihood of their occurrence. Dialogue between scientists and stakeholders is required to establish whether, and how, this science could play a role in the WIM.

Stakeholder perceptions of event attribution in the loss and damage debate

In 2013 the Warsaw International Mechanism (WIM) for loss and damage (L&D) associated with climate change impacts was established under the United Nations Framework Convention on Climate Change (UNFCCC). For scientists, L&D raises ques- tions around the extent that such impacts can be attributed to anthropogenic climate change, which may generate complex results and be controversial in the policy arena. This is particularly true in the case of probabilistic event attribution (PEA) science, a new and rapidly evolving field that assesses whether changes in the probabilities of extreme events are attributable to GHG emissions. If the potential applications of PEA are to be considered responsibly, dialogue between scientists and policy makers is fundamental. Two key questions are considered here through a literature review and key stakeholder interviews with representatives from the science and policy sectors underpinning L&D. These provided the opportunity for in-depth insights into stakeholders’ views on firstly, how much is known and understood about PEA by those associated with the L&D debate? Secondly, how might PEA inform L&D and wider climate policy? Results show debate within the climate science community, and limited understanding among other stakeholders, around the sense in which extreme events can be attributed to climate change. However, stake- holders do identify and discuss potential uses for PEA in the WIM and wider policy, but it remains difficult to explore precise applications given the ambiguity surrounding L&D. This implies a need for stakeholders to develop greater understandings of alternative conceptions of L&D and the role of science, and also identify how PEA can best be used to support policy, and address associated challenges.

p22phox C242T SNP inhibits inflammatory oxidative damage to endothelial cells and vessels

Background— T NADPH oxidase, by generating reactive oxygen species, is involved in the pathophysiology of many cardiovascular diseases and represents a therapeutic target for the development of novel drugs. A single-nucleotide polymorphism (SNP) C242T of the p22phox subunit of NADPH oxidase has been reported to be negatively associated with coronary heart disease (CHD) and may predict disease prevalence. However, the underlying mechanisms remain unknown. Methods and Results— Using computer molecular modelling we discovered that C242T SNP causes significant structural changes in the extracellular loop of p22phox and reduces its interaction stability with Nox2 subunit. Gene transfection of human pulmonary microvascular endothelial cells showed that C242T p22phox reduced significantly Nox2 expression but had no significant effect on basal endothelial O2.- production or the expression of Nox1 and Nox4. When cells were stimulated with TNFα (or high glucose), C242T p22phox inhibited significantly TNFα-induced Nox2 maturation, O2.- production, MAPK and NFκB activation and inflammation (all p<0.05). These C242T effects were further confirmed using p22phox shRNA engineered HeLa cells and Nox2-/- coronary microvascular endothelial cells. Clinical significance was investigated using saphenous vein segments from non CHD subjects after phlebectomies. TT (C242T) allele was common (prevalence of ~22%) and compared to CC, veins bearing TT allele had significantly lower levels of Nox2 expression and O2.- generation in response to high glucose challenge. Conclusions— C242T SNP causes p22phox structural changes that inhibit endothelial Nox2 activation and oxidative response to TNFα or high glucose stimulation. C242T SNP may represent a natural protective mechanism against inflammatory cardiovascular diseases.

Polymer-drug conjugates for combination anticancer therapy: investigating the mechanism of action.

We developed a family of polymer-drug conjugates carrying the combination of the anticancer agent epirubicin (EPI) and nitric oxide (NO). EPI-PEG-(NO)8, carrying the highest content of NO, displayed greater activity in Caco-2 cells while it decreased toxicity against endothelium cells and cardiomyocytes with respect to free EPI. FACS and confocal microscopy confirmed conjugates internalization. Light scattering showed formation of micelle whose size correlated with internalization rate. EPI-PEG-(NO)8 showed increased bioavailability in mice compared to free EPI.

The formation mechanism of the Bonin high in August

The Bonin high is a subtropical anticyclone that is predominant near Japan in the summer. This anticyclone is associated with an equivalent-barotropic structure, often extending throughout the entire troposphere. Although the equivalent-barotropic structure of the Bonin high has been known for years among synopticians because of its importance to the summer climate in east Asia, there are few dynamical explanations for such a structure. The present paper attempts to provide a formation mechanism for the deep ridge near Japan. We propose a new hypothesis that this equivalent-barotropic ridge near Japan is formed as a result of the propagation of stationary Rossby waves along the Asian jet in the upper troposphere (‘the Silk Road pattern’). First, the monthly mean climatology is examined in order to demonstrate this hypothesis. It is shown that the enhanced Asian jet in August is favourable for the propagation of stationary Rossby waves and that the regions of descent over the eastern Mediterranean Sea and the Aral Sea act as two major wave sources. Second, a primitive-equation model is used to simulate the climatology of August. The model successfully simulates the Bonin high with an equivalent-barotropic structure. The upper-tropospheric ridge is found to be enhanced by a height anomaly of more than 80 m at 200 hPa, when a wave packet arrives. Sensitivity experiments are conducted to show that the removal of the diabatic cooling over the Asian jet suppresses the Silk Road pattern and formation of an equivalent-barotropic ridge near Japan, while the removal of the diabatic heating in the western Pacific does not. Copyright © 2003 Royal Meteorological Society