Climate change impacts and adaptive strategies: lessons from the grapevine

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordThe cultivation of grapevines for winemaking, known as viticulture, is widely cited as a climate-sensitive agricultural system that has been used as an indicator of both historic and contemporary climate change. Numerous studies have questioned the viability of major viticulture regions under future climate projections. We review the methods used to study the impacts of climate change on viticulture in the light of what is known about the effects of climate and weather on the yields and quality of vineyard harvests. Many potential impacts of climate change on viticulture, particularly those associated with a change in climate variability or seasonal weather patterns, are rarely captured. Key biophysical characteristics of viticulture are often unaccounted for, including the variability of grapevine phenology and the exploitation of microclimatic niches that permit successful cultivation under suboptimal macroclimatic conditions. We consider how these same biophysical characteristics permit a variety of strategies by which viticulture can adapt to changing climatic conditions. The ability to realize these strategies, however, is affected by uneven exposure to risks across the winemaking sector, and the evolving capacity for decision-making within and across organizational boundaries. The role grape provenance plays in shaping perceptions of wine value and quality illustrates how conflicts of interest influence decisions about adaptive strategies within the industry. We conclude by considering what lessons can be taken from viticulture for studies of climate change impacts and the capacity for adaptation in other agricultural and natural systems

Reflexive practice and the making of elite business careers

Post-print version. Final version published by Sage; available online at http://mlq.sagepub.com/This paper develops a new perspective on reflexive practice in the making of elite business careers. It builds upon Bourdieu’s practice framework to examine how business leaders from elite and non-elite backgrounds develop and practice reflexivity in their everyday lives. The paper draws upon in-depth life-history interviews with members of the British business elite. Elites exhibited five types of reflexive behaviour, from which two modes of reflexive practice were derived: an accumulative mode, through which business leaders reflexively accumulate capital, positions and perspectives; and a re-constructive mode, through which they re-constitute the self in response to contingences, contexts and insights gathered. Our analysis suggests a link between reflexivity and career advancement, particularly in the case of non-privileged elites. Their greater experience of navigating the social landscape may facilitate perspective-taking, enhancing multipositionality, enabling such individuals to seize opportunities previously unthinkable

JNK signalling in cancer: In need of new, smarter therapeutic targets

Copyright © 2013 The British Pharmacological Society. This is the accepted version of the following article: Bubici, C. and Papa, S. (2014), JNK signalling in cancer: in need of new, smarter therapeutic targets. British Journal of Pharmacology, 171: 24–37, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/bph.12432/abstract.The JNKs are master protein kinases that regulate many physiological processes, including inflammatory responses, morphogenesis, cell proliferation, differentiation, survival and death. It is increasingly apparent that persistent activation of JNKs is involved in cancer development and progression. Therefore, JNKs represent attractive targets for therapeutic intervention with small molecule kinase inhibitors. However, evidence supportive of a tumour suppressor role for the JNK proteins has also been documented. Recent studies showed that the two major JNK proteins, JNK1 and JNK2, have distinct or even opposing functions in different types of cancer. As such, close consideration of which JNK proteins are beneficial targets and, more importantly, what effect small molecule inhibitors of JNKs have on physiological processes, are essential. A number of ATP-competitive and ATP-non-competitive JNK inhibitors have been developed, but have several limitations such as a lack of specificity and cellular toxicity. In this review, we summarize the accumulating evidence supporting a role for the JNK proteins in the pathogenesis of different solid and haematological malignancies, and discuss many challenges and scientific opportunities in the targeting of JNKs in cancer.Kay Kendall Leukemia Fund, Italian Association for Cancer Research and Foundation for Liver Research

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

Identification of Herbig Ae/Be Stars in the Small Magellanic Cloud

Protoplanetary disks orbiting intermediate-mass stars, Herbig Ae/Be stars, that have formed in a metal-poor environment may evolve differently than their Galactic cousins. A study of the planet-formation process in such an environment requires identification and characterization of a sample of candidates. We have observed several stars in the Small Magellanic Cloud, a nearby metal-poor dwarf galaxy, that have optical spectral properties of Herbig Ae/Be stars, including strong Hα emission, blue continuum excess, and spectral types ranging from early G to B. Infrared spectra of these sources from the Spitzer Space Telescope show strong excess emission indicating the presence of silicate dust, molecular and atomic gas, and polycyclic aromatic hydrocarbons. We present an analysis of the likelihood that these candidates are Herbig Ae/Be stars. This identification is the necessary first step to future investigations that will examine the role of metallicity in the evolution of protoplanetary disks

Collateral fattening in body composition autoregulation: its determinants and significance for obesity predisposition

Collateral fattening refers to the process whereby excess fat is deposited as a result of the body’s attempt to counter a deficit in lean mass through overeating. Its demonstration and significance to weight regulation and obesity can be traced to work on energy budget strategies in growing mammals and birds, and to men recovering from experimental starvation. The cardinal features of collateral fattening rests upon (i) the existence of a feedback system between lean tissue and appetite control, with lean tissue deficit driving hyperphagia, and (ii) upon the occurrence of a temporal desynchronization in the recovery of body composition, with complete recovery of fat mass preceeding that of lean mass. Under these conditions, persistent hyperphagia driven by the need to complete the recovery of lean tissue will result in the excess fat deposition (hence collateral fattening) and fat overshooting. After reviewing the main lines of evidence for the phenomenon of collateral fattening in body composition autoregulation, this article discusses the causes and determinants of the desynchronization in fat and lean tissue recovery leading to collateral fattening and fat overshooting, and points to their significance in the mechanisms by which dieting, developmental programming and sedentariness predispose to obesity

Conversion of Vertical Banded Gastroplasty to Roux-en-Y Gastric Bypass Results in Restoration of the Positive Effect on Weight Loss and Co-morbidities: Evaluation of 101 Patients

BACKGROUND: Vertical banded gastroplasty (VBG) is a widely used restrictive procedure in bariatric surgery. However, the re-operation rate after this operation is high. In the case of VBG failure, a conversion to Roux-en-Y gastric bypass (RYGBP) is an option. A study was undertaken to evaluate the results of the conversion from VBG to RYGBP. METHODS: 101 patients had conversion from VBG to RYGBP. Patients were separated into 3 groups, based on the indication for conversion: weight regain (group 1), excessive weight loss (group 2) and severe eating difficulties (group 3). Data for the study were collected by retrospective analysis of prospectively recorded data. RESULTS: Weight regain (group 1) was the reason for conversion in 73.3% of patients. Staple-line disruption was the most important cause for the weight regain (74.3%). Excessive weight loss (group 2) affected 14% of patients and was caused by outlet stenosis in 78.6% of patients. The remaining 13% had severe eating difficulties as a result of outlet stenosis (46.1%), pouch dilatation (30.8%) and pouch diverticula (23.1%). Mean BMI before conversion to RYGBP was 40.5, 22.3 and 29.8 kg/m2 in group 1, 2 and 3, respectively. Minor or major direct postoperative complications were observed in 2.0% to 7.0%. Long-term complications were more frequent, and consisted mainly of anastomotic stenosis (22.7%) and incisional hernia (16.8%). Follow-up after conversion was achieved in all patients (100%), with a mean period of 38 +/- 29 months. BMI decreased from 40.5 to 30.1 kg/m2, increased from 22.3 to 25.3 kg/m2. and decreased slightly from 29.8 to 29.0 kg/m2 in group 1, 2 and 3, respectively. All patients in group 3 noticed an improvement in eating difficulties. CONCLUSION: Complications after conversion from failed VBG to RYGBP are substantial and need to be considered. However, the conversion itself is a successful operation in terms of effect on body weight and treating eating difficulties after VBG

Bacterial Biodiversity-Ecosystem Functioning Relations Are Modified by Environmental Complexity

Peer reviewedPublisher PD

No evidence for association with APOL1 kidney disease risk alleles and Human African Trypanosomiasis in two Ugandan populations:

Human African trypanosomiasis (HAT) manifests as an acute form caused by Trypanosoma brucei rhodesiense (Tbr) and a chronic form caused by Trypanosoma brucei gambiense (Tbg). Previous studies have suggested a host genetic role in infection outcomes, particularly for APOL1. We have undertaken a candidate gene association studies (CGAS) in a Ugandan Tbr and a Tbg HAT endemic area, to determine whether polymorphisms in IL10, IL8, IL4, HLAG, TNFA, TNX4LB, IL6, IFNG, MIF, APOL1, HLAA, IL1B, IL4R, IL12B, IL12R, HP, HPR, and CFH have a role in HAT