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941.
Nicola Dalbeth Meaghan E House Gregory D Gamble Bregina Pool Anne Horne Lauren Purvis Angela Stewart Marilyn Merriman Murray Cadzow Amanda Phipps-Green Tony R Merriman 《Arthritis research & therapy》2014,16(1):R34
Introduction
Both genetic variation in ATP-binding cassette sub-family G member 2 (ABCG2) and intake of fructose-containing beverages are major risk factors for hyperuricemia and gout. This study aimed to test the hypothesis that the ABCG2 gout risk allele 141 K promotes the hyperuricaemic response to fructose loading.Methods
Healthy volunteers (n = 74) provided serum and urine samples immediately before and 30, 60, 120 and 180 minutes after ingesting a 64 g fructose solution. Data were analyzed based on the presence or absence of the ABCG2 141 K gout risk allele.Results
The 141 K risk allele was present in 23 participants (31%). Overall, serum urate (SU) concentrations during the fructose load were similar in those with and without the 141 K allele (PSNP = 0.15). However, the 141 K allele was associated with a smaller increase in SU following fructose intake (PSNP <0.0001). Those with the 141 K allele also had a smaller increase in serum glucose following the fructose load (PSNP = 0.002). Higher fractional excretion of uric acid (FEUA) at baseline and throughout the fructose load was observed in those with the 141 K risk allele (PSNP <0.0001). However, the change in FEUA in response to fructose was not different in those with and without the 141 K risk allele (PSNP = 0.39). The 141 K allele effects on serum urate and glucose were more pronounced in Polynesian participants and in those with a body mass index ≥25 kg/m2.Conclusions
In contrast to the predicted responses for a hyperuricemia/gout risk allele, the 141 K allele is associated with smaller increases in SU and higher FEUA following a fructose load. The results suggest that ABCG2 interacts with extra-renal metabolic pathways in a complex manner to regulate SU and gout risk.Clinical Trials Registration
The study was registered by the Australian Clinical Trials Registry (ACTRN12610001036000). 相似文献942.
Daniela Di Giuseppe Andrea Discacciati Nicola Orsini Alicja Wolk 《Arthritis research & therapy》2014,16(2):R61
Introduction
Although previous studies found that cigarette smoking is associated with risk of rheumatoid arthritis (RA), the dose-response relationship remains unclear. This meta-analysis quantitatively summarizes accumulated evidence regarding the association of lifelong exposure to cigarette smoking assessed as pack-years with the risk of RA.Methods
Relevant studies were identified by a search of MEDLINE and EMBASE from 1966 to October 2013, with no restrictions. Reference lists from retrieved articles were also reviewed. Studies that reported relative risks (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between pack-years of cigarette smoking and rheumatoid arthritis were included in a dose-response random-effects meta-regression analysis.Results
We included 3 prospective cohorts and 7 case-control studies in the meta-analysis. They included a total of 4,552 RA cases. There was no indication of heterogeneity (Pheterogeneity = 0.32) and publication bias did not affect the results. Compared to never smokers, the risk of developing RA increased by 26% (RR = 1.26, 95% CI 1.14 to 1.39) among those who smoked 1 to 10 pack-years and doubled among those with more than 20 pack-years (RR for 21 to 30 pack years = 1.94, 95% CI 1.65 to 2.27). The risk of RA was not increasing further for higher exposure levels (RR for >40 pack-years = 2.07, 95% CI 1.15 to 3.73). The risk of RA was statistically significantly higher among rheumatoid factor (RF)-positive RA cases (RR = 2.47, 95% CI 2.02 to 3.02) compared to RF-negative (RR = 1.58, 95% CI 1.15 to 2.18) when comparing the highest versus lowest category of pack-years for the individual studies.Conclusions
Lifelong cigarette smoking was positively associated with the risk of RA even among smokers with a low lifelong exposure. The risk of RA did not further increase with an exposure higher than 20 pack-years. 相似文献943.
Sahra Talamo Marco Peresani Matteo Romandini Rossella Duches Camille Jéquier Nicola Nannini Andreas Pastoors Andrea Picin Manuel Vaquero Gerd-Christian Weniger Jean-Jacques Hublin 《PloS one》2014,9(4)
In the northern Adriatic regions, which include the Venetian region and the Dalmatian coast, late Neanderthal settlements are recorded in few sites and even more ephemeral are remains of the Mid-Upper Palaeolithic occupations. A contribution to reconstruct the human presence during this time range has been produced from a recently investigated cave, Rio Secco, located in the northern Adriatic region at the foot of the Carnic Pre-Alps. Chronometric data make Rio Secco a key site in the context of recording occupation by late Neanderthals and regarding the diffusion of the Mid-Upper Palaeolithic culture in a particular district at the border of the alpine region. As for the Gravettian, its diffusion in Italy is a subject of on-going research and the aim of this paper is to provide new information on the timing of this process in Italy. In the southern end of the Peninsula the first occupation dates to around 28,000 14C BP, whereas our results on Gravettian layer range from 29,390 to 28,995 14C years BP. At the present state of knowledge, the emergence of the Gravettian in eastern Italy is contemporaneous with several sites in Central Europe and the chronological dates support the hypothesis that the Swabian Gravettian probably dispersed from eastern Austria. 相似文献
944.
Isabelle M. C?té Emily S. Darling Luis Malpica-Cruz Nicola S. Smith Stephanie J. Green Jocelyn Curtis-Quick Craig Layman 《PloS one》2014,9(4)
As a result of being hunted, animals often alter their behaviour in ways that make future encounters with predators less likely. When hunting is carried out for conservation, for example to control invasive species, these behavioural changes can inadvertently impede the success of future efforts. We examined the effects of repeated culling by spearing on the behaviour of invasive predatory lionfish (Pterois volitans/miles) on Bahamian coral reef patches. We compared the extent of concealment and activity levels of lionfish at dawn and midday on 16 coral reef patches off Eleuthera, The Bahamas. Eight of the patches had been subjected to regular daytime removals of lionfish by spearing for two years. We also estimated the distance at which lionfish became alert to slowly approaching divers on culled and unculled reef patches. Lionfish on culled reefs were less active and hid deeper within the reef during the day than lionfish on patches where no culling had occurred. There were no differences at dawn when removals do not take place. Lionfish on culled reefs also adopted an alert posture at a greater distance from divers than lionfish on unculled reefs. More crepuscular activity likely leads to greater encounter rates by lionfish with more native fish species because the abundance of reef fish outside of shelters typically peaks at dawn and dusk. Hiding deeper within the reef could also make remaining lionfish less likely to be encountered and more difficult to catch by spearfishers during culling efforts. Shifts in the behaviour of hunted invasive animals might be common and they have implications both for the impact of invasive species and for the design and success of invasive control programs. 相似文献
945.
Nicola Tambasco Marco Muti Pietro Chiarini Roberto Tarducci Stefano Caproni Anna Castrioto Pasquale Nigro Lucilla Parnetti Pietro Floridi Aroldo Rossi Paolo Calabresi 《PloS one》2014,9(5)
Background and Purpose
Wearing-off is one of the most frequent problems encountered by levodopa-treated patients. Entacapone, a peripheral inhibitor of catechol-O-methyltransferase (COMT), reduces this motor complication by prolonging the effect of levodopa. We sought to understand the impact of COMT-inhibition on movement execution in PD patients with wearing-off by comparing functional magnetic resonance imaging (f-MRI) activation patterns prior to and during entacapone treatment. Our hypothesis was to determine whether changes in cortical activation are associated to COMT-inhibitor treatment.Methods
Nine levodopa-treated non-demented PD patients with wearing-off were prospectively studied in two f-MRI session, prior to and during entacapone treatment. A group of control subjects were also studied for comparison.Results
The patients significantly improved under COMT-inhibitor treatment based on home diaries. F-MRI results showed that at baseline the patients presented a bilateral activation of the primary motor, controlateral premotor cortex and supplementary motor area, as well as ipsilateral cerebellum. During treatment with entacapone, PD patients showed reductions in the activations of these cortical areas and a decreased activation in the ipsilateral cerebellum.Conclusions
Our preliminary findings indicate that f-MRI is able to detect cortical activation changes during long-term modulation of dopaminergic treatment in PD patients with wearing-off, and thus, this technique could be further investigated in advanced PD patients. 相似文献946.
Georges Habineza Ndikuyeze Anita Gaurnier-Hausser Reema Patel Albert S. Baldwin Michael J. May Patrick Flood Erika Krick Kathleen J. Propert Nicola J. Mason 《PloS one》2014,9(5)
Activated B-Cell (ABC) Diffuse Large B-Cell Lymphoma (DLBCL) is a common, aggressive and poorly chemoresponsive subtype of DLBCL, characterized by constitutive canonical NF-κB signaling. Inhibition of NF-κB signaling leads to apoptosis of ABC-DLBCL cell lines, suggesting targeted disruption of this pathway may have therapeutic relevance. The selective IKK inhibitor, NEMO Binding Domain (NBD) peptide effectively blocks constitutive NF-κB activity and induces apoptosis in ABC-DLBCL cells in vitro. Here we used a comparative approach to determine the safety and efficacy of systemic NBD peptide to inhibit constitutive NF-κB signaling in privately owned dogs with spontaneous newly diagnosed or relapsed ABC-like DLBCL. Malignant lymph nodes biopsies were taken before and twenty-four hours after peptide administration to determine biological effects. Intravenous administration of <2 mg/kg NBD peptide was safe and inhibited constitutive canonical NF-κB activity in 6/10 dogs. Reductions in mitotic index and Cyclin D expression also occurred in a subset of dogs 24 hours post peptide and in 3 dogs marked, therapeutically beneficial histopathological changes were identified. Mild, grade 1 toxicities were noted in 3 dogs at the time of peptide administration and one dog developed transient subclinical hepatopathy. Long term toxicities were not identified. Pharmacokinetic data suggested rapid uptake of peptide into tissues. No significant hematological or biochemical toxicities were identified. Overall the results from this phase I study indicate that systemic administration of NBD peptide is safe and effectively blocks constitutive NF-κB signaling and reduces malignant B cell proliferation in a subset of dogs with ABC-like DLBCL. These results have potential translational relevance for human ABC-DLBCL. 相似文献
947.
Ailbhe M. McDermott Nicola Miller Deirdre Wall Lorcan M. Martyn Graham Ball Karl J. Sweeney Michael J. Kerin 《PloS one》2014,9(1)
Introduction
Breast cancer is a common disease with distinct tumor subtypes phenotypically characterized by ER and HER2/neu receptor status. MiRNAs play regulatory roles in tumor initiation and progression, and altered miRNA expression has been demonstrated in a variety of cancer states presenting the potential for exploitation as cancer biomarkers. Blood provides an excellent medium for biomarker discovery. This study investigated systemic miRNAs differentially expressed in Luminal A-like (ER+PR+HER2/neu-) breast cancer and their effectiveness as oncologic biomarkers in the clinical setting.Methods
Blood samples were prospectively collected from patients with Luminal A-like breast cancer (n = 54) and controls (n = 56). RNA was extracted, reverse transcribed and subjected to microarray analysis (n = 10 Luminal A-like; n = 10 Control). Differentially expressed miRNAs were identified by artificial neural network (ANN) data-mining algorithms. Expression of specific miRNAs was validated by RQ-PCR (n = 44 Luminal A; n = 46 Control) and potential relationships between circulating miRNA levels and clinicopathological features of breast cancer were investigated.Results
Microarray analysis identified 76 differentially expressed miRNAs. ANN revealed 10 miRNAs for further analysis (miR-19b, miR-29a, miR-93, miR-181a, miR-182, miR-223, miR-301a, miR-423-5p, miR-486-5 and miR-652). The biomarker potential of 4 miRNAs (miR-29a, miR-181a, miR-223 and miR-652) was confirmed by RQ-PCR, with significantly reduced expression in blood of women with Luminal A-like breast tumors compared to healthy controls (p = 0.001, 0.004, 0.009 and 0.004 respectively). Binary logistic regression confirmed that combination of 3 of these miRNAs (miR-29a, miR-181a and miR-652) could reliably differentiate between cancers and controls with an AUC of 0.80.Conclusion
This study provides insight into the underlying molecular portrait of Luminal A-like breast cancer subtype. From an initial 76 miRNAs, 4 were validated with altered expression in the blood of women with Luminal A-like breast cancer. The expression profiles of these 3 miRNAs, in combination with mammography, has potential to facilitate accurate subtype-specific breast tumor detection. 相似文献948.
Don A. Driscoll Sam C. Banks Philip S. Barton Karen Ikin Pia Lentini David B. Lindenmayer Annabel L. Smith Laurence E. Berry Emma L. Burns Amanda Edworthy Maldwyn J. Evans Rebecca Gibson Rob Heinsohn Brett Howland Geoff Kay Nicola Munro Ben C. Scheele Ingrid Stirnemann Dejan Stojanovic Nici Sweaney Nélida R. Villase?or Martin J. Westgate 《PloS one》2014,9(4)
Dispersal knowledge is essential for conservation management, and demand is growing. But are we accumulating dispersal knowledge at a pace that can meet the demand? To answer this question we tested for changes in dispersal data collection and use over time. Our systematic review of 655 conservation-related publications compared five topics: climate change, habitat restoration, population viability analysis, land planning (systematic conservation planning) and invasive species. We analysed temporal changes in the: (i) questions asked by dispersal-related research; (ii) methods used to study dispersal; (iii) the quality of dispersal data; (iv) extent that dispersal knowledge is lacking, and; (v) likely consequences of limited dispersal knowledge. Research questions have changed little over time; the same problems examined in the 1990s are still being addressed. The most common methods used to study dispersal were occupancy data, expert opinion and modelling, which often provided indirect, low quality information about dispersal. Although use of genetics for estimating dispersal has increased, new ecological and genetic methods for measuring dispersal are not yet widely adopted. Almost half of the papers identified knowledge gaps related to dispersal. Limited dispersal knowledge often made it impossible to discover ecological processes or compromised conservation outcomes. The quality of dispersal data used in climate change research has increased since the 1990s. In comparison, restoration ecology inadequately addresses large-scale process, whilst the gap between knowledge accumulation and growth in applications may be increasing in land planning. To overcome apparent stagnation in collection and use of dispersal knowledge, researchers need to: (i) improve the quality of available data using new approaches; (ii) understand the complementarities of different methods and; (iii) define the value of different kinds of dispersal information for supporting management decisions. Ambitious, multi-disciplinary research programs studying many species are critical for advancing dispersal research. 相似文献
949.
Erin Bargerstock Vikram Puvenna Philip Iffland Tatiana Falcone Mohammad Hossain Stephen Vetter Shumei Man Leah Dickstein Nicola Marchi Chaitali Ghosh Juliana Carvalho-Tavares Damir Janigro 《PloS one》2014,9(7)
S100B is a reporter of blood-brain barrier (BBB) integrity which appears in blood when the BBB is breached. Circulating S100B derives from either extracranial sources or release into circulation by normal fluctuations in BBB integrity or pathologic BBB disruption (BBBD). Elevated S100B matches the clinical presence of indices of BBBD (gadolinium enhancement or albumin coefficient). After repeated sub-concussive episodes, serum S100B triggers an antigen-driven production of anti-S100B autoantibodies. We tested the hypothesis that the presence of S100B in extracranial tissue is due to peripheral cellular uptake of serum S100B by antigen presenting cells, which may induce the production of auto antibodies against S100B. To test this hypothesis, we used animal models of seizures, enrolled patients undergoing repeated BBBD, and collected serum samples from epileptic patients. We employed a broad array of techniques, including immunohistochemistry, RNA analysis, tracer injection and serum analysis. mRNA for S100B was segregated to barrier organs (testis, kidney and brain) but S100B protein was detected in immunocompetent cells in spleen, thymus and lymph nodes, in resident immune cells (Langerhans, satellite cells in heart muscle, etc.) and BBB endothelium. Uptake of labeled S100B by rat spleen CD4+ or CD8+ and CD86+ dendritic cells was exacerbated by pilocarpine-induced status epilepticus which is accompanied by BBBD. Clinical seizures were preceded by a surge of serum S100B. In patients undergoing repeated therapeutic BBBD, an autoimmune response against S100B was measured. In addition to its role in the central nervous system and its diagnostic value as a BBBD reporter, S100B may integrate blood-brain barrier disruption to the control of systemic immunity by a mechanism involving the activation of immune cells. We propose a scenario where extravasated S100B may trigger a pathologic autoimmune reaction linking systemic and CNS immune responses. 相似文献
950.
Nicola Saino Maria Romano Diego Rubolini Roberto Ambrosini Andrea Romano Manuela Caprioli Alessandra Costanzo Gaia Bazzi 《PloS one》2014,9(5)
Physiological trade-offs mediated by limiting energy, resources or time constrain the simultaneous expression of major functions and can lead to the evolution of temporal separation between demanding activities. In birds, plumage renewal is a demanding activity, which accomplishes fundamental functions, such as allowing thermal insulation, aerodynamics and socio-sexual signaling. Feather renewal is a very expensive and disabling process, and molt is often partitioned from breeding and migration. However, trade-offs between feather renewal and breeding have been only sparsely studied. In barn swallows (Hirundo rustica) breeding in Italy and undergoing molt during wintering in sub-Saharan Africa, we studied this trade-off by removing a tail feather from a large sample of individuals and analyzing growth bar width, reflecting feather growth rate, and length of the growing replacement feather in relation to the stage in the breeding cycle at removal and clutch size. Growth bar width of females and length of the growing replacement feather of both sexes were smaller when the original feather had been removed after clutch initiation. Importantly, in females both growth bar width and replacement feather length were negatively predicted by clutch size, and more strongly so for large clutches and when feather removal occurred immediately after clutch completion. Hence, we found strong, coherent evidence for a trade-off between reproduction, and laying effort in particular, and the ability to generate new feathers. These results support the hypothesis that the derived condition of molting during wintering in long-distance migrants is maintained by the costs of overlapping breeding and molt. 相似文献