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111.
Enrique Quintero Marta Carrillo Maria-Liz Leoz Joaquin Cubiella Carla Gargallo Angel Lanas Luis Bujanda Antonio Z. Gimeno-García Manuel Hernández-Guerra David Nicolás-Pérez Inmaculada Alonso-Abreu Juan Diego Morillas Francesc Balaguer Alfonso Muriel 《PLoS medicine》2016,13(5)
BackgroundFirst-degree relatives (FDR) of patients with colorectal cancer have a higher risk of developing colorectal cancer than the general population. For this reason, screening guidelines recommend colonoscopy every 5 or 10 y, starting at the age of 40, depending on whether colorectal cancer in the index-case is diagnosed at <60 or ≥60 y, respectively. However, studies on the risk of neoplastic lesions are inconclusive. The aim of this study was to determine the risk of advanced neoplasia (three or more non-advanced adenomas, advanced adenoma, or invasive cancer) in FDR of patients with colorectal cancer compared to average-risk individuals (i.e., asymptomatic adults 50 to 69 y of age with no family history of colorectal cancer).ConclusionsIndividuals having two FDR with colorectal cancer showed an increased risk of advanced neoplasia compared to those with average-risk for colorectal cancer. Men had over 2-fold higher risk of advanced neoplasia than women, independent of family history. These data suggest that screening colonoscopy guidelines should be revised in the familial-risk population. 相似文献
112.
Carla D. G. Borges Stephen J. Hawkins Tasman P. Crowe C. Patrick Doncaster 《Ecology and evolution》2016,6(2):514-531
Grazing mollusks are used as a food resource worldwide, and limpets are harvested commercially for both local consumption and export in several countries. This study describes a field experiment to assess the effects of simulated human exploitation of limpets Patella vulgata on their population ecology in terms of protandry (age‐related sex change from male to female), growth, recruitment, migration, and density regulation. Limpet populations at two locations in southwest England were artificially exploited by systematic removal of the largest individuals for 18 months in plots assigned to three treatments at each site: no (control), low, and high exploitation. The shell size at sex change (L50: the size at which there is a 50:50 sex ratio) decreased in response to the exploitation treatments, as did the mean shell size of sexual stages. Size‐dependent sex change was indicated by L50 occurring at smaller sizes in treatments than controls, suggesting an earlier switch to females. Mean shell size of P. vulgata neuters changed little under different levels of exploitation, while males and females both decreased markedly in size with exploitation. No differences were detected in the relative abundances of sexual stages, indicating some compensation for the removal of the bigger individuals via recruitment and sex change as no migratory patterns were detected between treatments. At the end of the experiment, 0–15 mm recruits were more abundant at one of the locations but no differences were detected between treatments. We conclude that sex change in P. vulgata can be induced at smaller sizes by reductions in density of the largest individuals reducing interage class competition. Knowledge of sex‐change adaptation in exploited limpet populations should underpin strategies to counteract population decline and improve rocky shore conservation and resource management. 相似文献
113.
Antonella Muscella Carla Vetrugno Luca Giulio Cossa Giovanna Antonaci Francesco De Nuccio Sandra Angelica De Pascali Francesco Paolo Fanizzi Santo Marsigliante 《PloS one》2016,11(11)
Malignant pleural mesothelioma (MPM) is an aggressive malignancy highly resistant to chemotherapy. There is an urgent need for effective therapy inasmuch as resistance, intrinsic and acquired, to conventional therapies is common. Among Pt(II) antitumor drugs, [Pt(O,O′-acac)(γ-acac)(DMS)] (Ptac2S) has recently attracted considerable attention due to its strong in vitro and in vivo antiproliferative activity and reduced toxicity. The purpose of this study was to examine the efficacy of Ptac2S treatment in MPM. We employed the ZL55 human mesothelioma cell line in vitro and in a murine xenograft model in vivo, to test the antitumor activity of Ptac2S. Cytotoxicity assays and Western blottings of different apoptosis and survival proteins were thus performed. Ptac2S increases MPM cell death in vitro and in vivo compared with cisplatin. Ptac2S was more efficacious than cisplatin also in inducing apoptosis characterized by: (a) mitochondria depolarization, (b) increase of bax expression and its cytosol-to-mitochondria translocation and decrease of Bcl-2 expression, (c) activation of caspase-7 and -9. Ptac2S activated full-length PKC-δ and generated a PKC-δ fragment. Full-length PKC-δ translocated to the nucleus and membrane, whilst PKC-δ fragment concentrated to mitochondria. Ptac2S was also responsible for the PKC-ε activation that provoked phosphorylation of p38. Both PKC-δ and PKC-ε inhibition (by PKC–siRNA) reduced the apoptotic death of ZL55 cells. Altogether, our results confirm that Ptac2S is a promising therapeutic agent for malignant mesothelioma, providing a solid starting point for its validation as a suitable candidate for further pharmacological testing. 相似文献
114.
Chao-Wu Xiao Carla M. Wood Eleonora Swist Reiko Nagasaka Kurtis Sarafin Claude Gagnon Lois Fernandez Sylvie Faucher Hong-Xing Wu Laura Kenney Walisundera M. N. Ratnayake 《PloS one》2016,11(1)
Objectives
This study compared cardio-metabolic disease risk factors and their associations with serum vitamin D and omega-3 status in South Asian (SAC) and White Canadians (WC) living in Canada’s capital region.Methods
Fasting blood samples were taken from 235 SAC and 279 WC aged 20 to 79 years in Ottawa, and 22 risk factors were measured.Results
SAC men and women had significantly higher fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), apolipoprotein B (ApoB), ratios of total (TC) to HDL cholesterol (HDLC) and ApoB to ApoA1, leptin, E-selectin, P-selectin, ICAM-1 and omega-3 (p < 0.05), but lower HDLC, ApoA1, vitamin D levels than WC (p < 0.05). SAC women had higher CRP and VEGF than WC women. Adequate (50–74.9 nmol/L) or optimal (≥ 75 nmol/L) levels of 25(OH)D were associated with lower BMI, glucose, insulin, HOMA-IR, TG, TC, low density lipoprotein cholesterol (LDLC), ApoB/ApoA1 ratio, CRP, leptin, and higher HDLC, ApoA1, omega-3 index, L-selectin levels in WC, but not in SAC. Intermediate (>4%-<8%) or high (≥ 8%) levels of omega-3 indices were related to lower E-selectin, P-selectin, ICAM-1 and higher HDLC, 25(OH)D levels in WC, but not in SAC. The BMIs of ≤ 25 kg/m2 were related to lower LDLC, ApoB, VEGF, creatinine and higher 25(OH)D in WC, but not in SAC.Conclusions
The associations of vitamin D, omega-3 status, BMI and risk factors were more profound in the WC than SAC. Compared to WC, vitamin D status and omega-3 index may not be good predictive risk factors for the prevalence of CVD and diabetes in SAC. 相似文献115.
Jilson L. Almeida-Junior Leonardo Gil-Santana Carolina A. M. Oliveira Simone Castro Aparecida S. Cafezeiro Carla Daltro Eduardo M. Netto Hardy Kornfeld Bruno B. Andrade 《PloS one》2016,11(4)
BackgroundDiabetes mellitus (DM) has been associated with increased risk for pulmonary tuberculosis (PTB) in endemic settings but it is unknown whether PTB risk is also increased by pre-DM. Here, we prospectively examined the association between glucose metabolism disorder (GMD) and PTB in patients with respiratory symptoms at a tuberculosis primary care reference center in Brazil.MethodsOral glucose tolerance test was performed and levels of fasting plasma glucose and glycohemoglobin (HbA1c) were measured in a cohort of 892 individuals presenting with respiratory symptoms of more than two weeks duration. Patients were also tested for PTB with sputum cultures. Prevalence of pre-DM and DM (based on HbA1c) was estimated and tested for association with incident PTB. Other TB risk factors including smoking history were analyzed.ResultsThe majority of the study population (63.1%) exhibited GMD based on HbA1c ≥5.7%. Patients with GMD had higher prevalence of PTB compared to normoglycemic patients. Individuals with DM exhibited increased frequency of TB-related symptoms and detection of acid-fast bacilli in sputum smears. Among patients with previous DM diagnosis, sustained hyperglycemia (HbA1c ≥7.0%) was associated with increased TB prevalence. Smoking history alone was not significantly associated with TB in our study population but the combination of smoking and HbA1c ≥7.0% was associated with 6 times higher odds for PTB.ConclusionsSustained hyperglycemia and pre-DM are independently associated with active PTB. This evidence raises the question whether improving glycemic control in diabetic TB patients would reduce the risk of TB transmission and simultaneously reduce the clinical burden of disease. A better understanding of mechanisms underlying these associations, especially those suggesting that pre-DM may be a factor driving susceptibility to TB is warranted. 相似文献
116.
Anna-Lena Volckmar Chung Ting Han Carolin Pütter Stefan Haas Carla I. G. Vogel Nadja Knoll Christoph Struve Maria G?bel Katharina Haas Nikolas Herrfurth Ivonne Jarick Harald Grallert Annette Schürmann Hadi Al-Hasani Johannes Hebebrand Sascha Sauer Anke Hinney 《PloS one》2016,11(2)
Introduction
Genes involved in body weight regulation that were previously investigated in genome-wide association studies (GWAS) and in animal models were target-enriched followed by massive parallel next generation sequencing.Methods
We enriched and re-sequenced continuous genomic regions comprising FTO, MC4R, TMEM18, SDCCAG8, TKNS, MSRA and TBC1D1 in a screening sample of 196 extremely obese children and adolescents with age and sex specific body mass index (BMI) ≥ 99th percentile and 176 lean adults (BMI ≤ 15th percentile). 22 variants were confirmed by Sanger sequencing. Genotyping was performed in up to 705 independent obesity trios (extremely obese child and both parents), 243 extremely obese cases and 261 lean adults.Results and Conclusion
We detected 20 different non-synonymous variants, one frame shift and one nonsense mutation in the 7 continuous genomic regions in study groups of different weight extremes. For SNP Arg695Cys (rs58983546) in TBC1D1 we detected nominal association with obesity (pTDT = 0.03 in 705 trios). Eleven of the variants were rare, thus were only detected heterozygously in up to ten individual(s) of the complete screening sample of 372 individuals. Two of them (in FTO and MSRA) were found in lean individuals, nine in extremely obese. In silico analyses of the 11 variants did not reveal functional implications for the mutations. Concordant with our hypothesis we detected a rare variant that potentially leads to loss of FTO function in a lean individual. For TBC1D1, in contrary to our hypothesis, the loss of function variant (Arg443Stop) was found in an obese individual. Functional in vitro studies are warranted. 相似文献117.
Carla Minguet-Parramona Yizhou Wang Adrian Hills Silvere Vialet-Chabrand Howard Griffiths Simon Rogers Tracy Lawson Virgilio L. Lew Michael R. Blatt 《Plant physiology》2016,170(1):33-42
Oscillations in cytosolic-free Ca2+ concentration ([Ca2+]i) have been proposed to encode information that controls stomatal closure. [Ca2+]i oscillations with a period near 10 min were previously shown to be optimal for stomatal closure in Arabidopsis (Arabidopsis thaliana), but the studies offered no insight into their origins or mechanisms of encoding to validate a role in signaling. We have used a proven systems modeling platform to investigate these [Ca2+]i oscillations and analyze their origins in guard cell homeostasis and membrane transport. The model faithfully reproduced differences in stomatal closure as a function of oscillation frequency with an optimum period near 10 min under standard conditions. Analysis showed that this optimum was one of a range of frequencies that accelerated closure, each arising from a balance of transport and the prevailing ion gradients across the plasma membrane and tonoplast. These interactions emerge from the experimentally derived kinetics encoded in the model for each of the relevant transporters, without the need of any additional signaling component. The resulting frequencies are of sufficient duration to permit substantial changes in [Ca2+]i and, with the accompanying oscillations in voltage, drive the K+ and anion efflux for stomatal closure. Thus, the frequency optima arise from emergent interactions of transport across the membrane system of the guard cell. Rather than encoding information for ion flux, these oscillations are a by-product of the transport activities that determine stomatal aperture.Stomata in the leaf epidermis are the main pathway both for CO2 entry for photosynthesis and for foliar water loss by transpiration. Guard cells surround the stomatal pore and regulate the aperture, balancing the often conflicting demands for CO2 and water conservation. Guard cells open and close the pore by expanding and contracting through the uptake and loss, respectively, of osmotic solutes, notably of K+, Cl−, and malate2− (Mal2−; Pandey et al., 2007; Kim et al., 2010; Roelfsema and Hedrich, 2010; Lawson and Blatt, 2014). These transport processes comprise the final effectors of a regulatory network that coordinates transport across the plasma membrane and tonoplast, and maintains the homeostasis of the guard cell. A number of well-defined signals—including light, CO2, drought and the water stress hormone abscisic acid (ABA)—act on this network, altering transport, solute content, turgor and cell volume, and ultimately stomatal aperture.Much research has focused on stomatal closure, underscoring both Ca2+-independent and Ca2+-dependent signaling. Of the latter, elevated cytosolic-free Ca2+ concentration ([Ca2+]i) inactivates inward-rectifying K+ channels (IK,in) to prevent K+ uptake and activates Cl− (anion) channels (ICl) at the plasma membrane to depolarize the membrane and engage K+ efflux through outward-rectifying K+ channels (IK,out; Keller et al., 1989; Blatt et al., 1990; Thiel et al., 1992; Lemtiri-Chlieh and MacRobbie, 1994). ABA, and most likely CO2 (Kim et al., 2010), elevate [Ca2+]i by facilitating Ca2+ entry at the plasma membrane to trigger Ca2+ release from endomembrane stores, a process often described as Ca2+-induced Ca2+ release (Grabov and Blatt, 1998, 1999). The hormone promotes Ca2+ influx by activating Ca2+ channels (ICa) at the plasma membrane, even in isolated membrane patches (Hamilton et al., 2000, 2001), which is linked to reactive oxygen species (Kwak et al., 2003; Wang et al., 2013). In parallel, cADP-ribose and nitric oxide promote endomembrane Ca2+ release and [Ca2+]i elevation (Leckie et al., 1998; Neill et al., 2002; Garcia-Mata et al., 2003; Blatt et al., 2007). Best estimates indicate that endomembrane release accounts for more than 95% of the Ca2+ entering the cytosol to raise [Ca2+]i (Chen et al., 2012; Wang et al., 2012).One feature of stomatal response to ABA, and indeed to a range of stimuli both hormonal as well as external, is its capacity for oscillations both in membrane voltage and [Ca2+]i. Guard cell [Ca2+]i at rest is typically around 100 to 200 nm, as it is in virtually all living cells. In response to ABA, [Ca2+]i can rise above 1 μm—and locally, most likely above 10 μm—often in cyclic transients of tens of seconds to several minutes’ duration in association with oscillations in voltage and stomatal closure (Gradmann et al., 1993; McAinsh et al., 1995; Webb et al., 1996; Grabov and Blatt, 1998, 1999; Staxen et al., 1999; Allen et al., 2001). In principle, cycling in voltage and [Ca2+]i arises as closure is accelerated with a controlled release of K+, Cl−, and Mal2− from the guard cell and is subject to extracellular ion concentrations (Gradmann et al., 1993; Chen et al., 2012). However, it has been proposed that these, and similar oscillations in a variety of plant cell models, serve as physiological signals in their own right (McAinsh et al., 1995; Ehrhardt et al., 1996; Taylor et al., 1996). In support of such a signaling role, experiments designed to impose [Ca2+]i (and voltage) oscillations in guard cells have yielded an optimal frequency for closure with a period near 10 min (Allen et al., 2001). Nonetheless, the studies offer no mechanistic explanation for this optimum that could validate a causal role in signaling, and none has been forthcoming since. Here we address questions of how such optimal frequencies in [Ca2+]i oscillation arise and their relevance for stomatal closure, using quantitative systems analysis of guard cell transport and homeostasis. Our findings indicate that oscillations in voltage and [Ca2+]i, and their optima associated with stomatal closure, are most simply explained as emerging from the interactions between ion transporters that drive stomatal closure. Thus, we conclude that these oscillations do not control, but are a by-product of the transport that determines stomatal aperture. 相似文献
118.
Carla D. Jorge Nuno Borges Irina Bagyan Andreas Bilstein Helena Santos 《Extremophiles : life under extreme conditions》2016,20(3):251-259
Protein misfolding, aggregation and deposition in the brain, in the form of amyloid, are implicated in the etiology of several neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and prion diseases. Drugs available on the market reduce the symptoms, but they are not a cure. Therefore, it is urgent to identify promising targets and develop effective drugs. Preservation of protein native conformation and/or inhibition of protein aggregation seem pertinent targets for drug development. Several studies have shown that organic solutes, produced by extremophilic microorganisms in response to osmotic and/or heat stress, prevent denaturation and aggregation of model proteins. Among these stress solutes, mannosylglycerate, mannosylglyceramide, di-myo-inositol phosphate, diglycerol phosphate and ectoine are effective in preventing amyloid formation by Alzheimer’s Aβ peptide and/or α-synuclein in vitro. Moreover, mannosylglycerate is a potent inhibitor of Aβ and α-synuclein aggregation in living cells, and mannosylglyceramide and ectoine inhibit aggregation and reduce prion peptide-induced toxicity in human cells. This review focuses on the efficacy of stress solutes from hyper/thermophiles and ectoines to prevent amyloid formation in vitro and in vivo and their potential application in drug development against protein misfolding diseases. Current and envisaged applications of these extremolytes in neurodegenerative diseases and healthcare will also be addressed. 相似文献
119.
Decker Helena Piermartiri Tetsade C. B. Nedel Cláudia B. Romão Luciana F. Francisco Sheila S. Dal-Cim Tharine Boeck Carina R. Moura-Neto Vivaldo Tasca Carla I. 《Purinergic signalling》2019,15(4):439-450
Purinergic Signalling - The guanine-based purines (GBPs) have essential extracellular functions such as modulation of glutamatergic transmission and trophic effects on neurons and astrocytes. We... 相似文献
120.
Sierk de Jong Mark Staples Carla Grobler Vassilis Daioglou Robert Malina Steven Barrett Ric Hoefnagels Andr Faaij Martin Junginger 《Global Change Biology Bioenergy》2019,11(2):427-443
The climate impact of bioenergy is commonly quantified in terms of CO2 equivalents, using a fixed 100‐year global warming potential as an equivalency metric. This method has been criticized for the inability to appropriately address emissions timing and the focus on a single impact metric, which may lead to inaccurate or incomplete quantification of the climate impact of bioenergy production. In this study, we introduce Dynamic Relative Climate Impact (DRCI) curves, a novel approach to visualize and quantify the climate impact of bioenergy systems over time. The DRCI approach offers the flexibility to analyze system performance for different value judgments regarding the impact category (e.g., emissions, radiative forcing, and temperature change), equivalency metric, and analytical time horizon. The DRCI curves constructed for fourteen bioenergy systems illustrate how value judgments affect the merit order of bioenergy systems, because they alter the importance of one‐time (associated with land use change emissions) versus sustained (associated with carbon debt or foregone sequestration) emission fluxes and short‐ versus long‐lived climate forcers. Best practices for bioenergy production (irrespective of value judgments) include high feedstock yields, high conversion efficiencies, and the application of carbon capture and storage. Furthermore, this study provides examples of production contexts in which the risk of land use change emissions, carbon debt, or foregone sequestration can be mitigated. For example, the risk of indirect land use change emissions can be mitigated by accompanying bioenergy production with increasing agricultural yields. Moreover, production contexts in which the counterfactual scenario yields immediate or additional climate impacts can provide significant climate benefits. This paper is accompanied by an Excel‐based calculation tool to reproduce the calculation steps outlined in this paper and construct DRCI curves for bioenergy systems of choice. 相似文献