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41.
Timm Intemann Kirsten Mehlig Stefaan De Henauw Alfonso Siani Tassos Constantinou Luis A. Moreno Dénes Molnár Toomas Veidebaum Iris Pigeot 《Biometrical journal. Biometrische Zeitschrift》2020,62(1):221-237
Modelling dietary data, and especially 24-hr dietary recall (24HDR) data, is a challenge. Ignoring the inherent measurement error (ME) leads to biased effect estimates when the association between an exposure and an outcome is investigated. We propose an adapted simulation extrapolation (SIMEX) algorithm for modelling dietary exposures. For this purpose, we exploit the ME model of the NCI method where we assume the assumption of normally distributed errors of the reported intake on the Box-Cox transformed scale and of unbiased recalls on the original scale. According to the SIMEX algorithm, remeasurements of the observed data with additional ME are generated in order to estimate the association between the level of ME and the resulting effect estimate. Subsequently, this association is extrapolated to the case of zero ME to obtain the corrected estimate. We show that the proposed method fulfils the key property of the SIMEX approach, that is, that the MSE of the generated data will converge to zero if the ME variance converges to zero. Furthermore, the method is applied to real 24HDR data of the I.Family study to correct the effects of salt and alcohol intake on blood pressure. In a simulation study, the method is compared with the NCI method resulting in effect estimates with either smaller MSE or smaller bias in certain situations. In addition, we found our method to be more informative and easier to implement. Therefore, we conclude that the proposed method is useful to promote the dissemination of ME correction methods in nutritional epidemiology. 相似文献
42.
Wibke Singer Annalisa Zuccotti Mirko Jaumann Sze Chim Lee Rama Panford-Walsh Hao Xiong Ulrike Zimmermann Christoph Franz Hyun-Soon Geisler Iris Köpschall Karin Rohbock Ksenya Varakina Sandrine Verpoorten Thomas Reinbothe Thomas Schimmang Lukas Rüttiger Marlies Knipper 《Molecular neurobiology》2013,47(1):261-279
Increasing evidence shows that hearing loss is a risk factor for tinnitus and hyperacusis. Although both often coincide, a causal relationship between tinnitus and hyperacusis has not been shown. Currently, tinnitus and hyperacusis are assumed to be caused by elevated responsiveness in subcortical circuits. We examined both the impact of different degrees of cochlear damage and the influence of stress priming on tinnitus induction. We used (1) a behavioral animal model for tinnitus designed to minimize stress, (2) ribbon synapses in inner hair cells (IHCs) as a measure for deafferentation, (3) the integrity of auditory brainstem responses (ABR) to detect differences in stimulus-evoked neuronal activity, (4) the expression of the activity-regulated cytoskeletal protein, Arc, to identify long-lasting changes in network activity within the basolateral amygdala (BLA), hippocampal CA1, and auditory cortex (AC), and (5) stress priming to investigate the influence of corticosteroid on trauma-induced brain responses. We observed that IHC ribbon loss (deafferentation) leads to tinnitus when ABR functions remain reduced and Arc is not mobilized in the hippocampal CA1 and AC. If, however, ABR waves are functionally restored and Arc is mobilized, tinnitus does not occur. Both central response patterns were found to be independent of a profound threshold loss and could be shifted by the corticosterone level at the time of trauma. We, therefore, discuss the findings in the context of a history of stress that can trigger either an adaptive or nonadaptive brain response following injury. 相似文献
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44.
Iris Postmus Stella Trompet Anton J. M. de Craen Brendan M. Buckley Ian Ford David J. Stott Naveed Sattar P. Eline Slagboom Rudi G. J. Westendorp J. Wouter Jukema 《Journal of lipid research》2013,54(2):561-566
Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) is a protein involved in LDL-cholesterol metabolism. The single-nucleotide polymorphism (SNP) rs11591147 has been associated with lower LDL-cholesterol and a lower risk of coronary heart disease. Because PCSK9 has high affinity to the LDL receptor, inhibiting PCSK9 is a testable therapeutic target for lipid-lowering therapy. Currently, several approaches to inhibit PCSK9 are under development, but it is unknown what the effects of those inhibitors will be on cognition or noncardiovascular clinical events. In this study, we assessed the association between rs11591147 and cognitive performance, activities of daily living (ADL), and noncardiovascular clinical events within 5,777 participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Rs11591147 was associated with 10% to 16% lower LDL cholesterol levels (P = 3.62 × 10−12), but was not associated with cognitive performance, ADL, or noncardiovascular clinical events in the PROSPER study. Our findings suggest that lower cholesterol levels due to genetic variation in the PCSK9 gene are not associated with cognitive performance, functional status, or noncardiovascular clinical events. 相似文献
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46.
Daniela Valenti Domenico De Rasmo Anna Signorile Leonardo Rossi Lidia de Bari Iris Scala Barbara Granese Sergio Papa Rosa Anna Vacca 《生物化学与生物物理学报:疾病的分子基础》2013,1832(4):542-552
A critical role for mitochondrial dysfunction has been proposed in the pathogenesis of Down's syndrome (DS), a human multifactorial disorder caused by trisomy of chromosome 21, associated with mental retardation and early neurodegeneration. Previous studies from our group demonstrated in DS cells a decreased capacity of the mitochondrial ATP production system and overproduction of reactive oxygen species (ROS) in mitochondria. In this study we have tested the potential of epigallocatechin-3-gallate (EGCG) – a natural polyphenol component of green tea – to counteract the mitochondrial energy deficit found in DS cells. We found that EGCG, incubated with cultured lymphoblasts and fibroblasts from DS subjects, rescued mitochondrial complex I and ATP synthase catalytic activities, restored oxidative phosphorylation efficiency and counteracted oxidative stress. These effects were associated with EGCG-induced promotion of PKA activity, related to increased cellular levels of cAMP and PKA-dependent phosphorylation of the NDUFS4 subunit of complex I. In addition, EGCG strongly promoted mitochondrial biogenesis in DS cells, as associated with increase in Sirt1-dependent PGC-1α deacetylation, NRF-1 and T-FAM protein levels and mitochondrial DNA content.In conclusion, this study shows that EGCG is a promoting effector of oxidative phosphorylation and mitochondrial biogenesis in DS cells, acting through modulation of the cAMP/PKA- and sirtuin-dependent pathways. EGCG treatment promises thus to be a therapeutic approach to counteract mitochondrial energy deficit and oxidative stress in DS. 相似文献
47.
Victor Vendrell Citlali Vázquez-Echeverría Iris López-Hernández Beatriz Durán Alonso Salvador Martinez Cristina Pujades Thomas Schimmang 《Mechanisms of development》2013,130(2-3):160-168
Fgf and Wnt signalling have been shown to be required for formation of the otic placode in vertebrates. Whereas several Fgfs including Fgf3, Fgf8 and Fgf10 have been shown to participate during early placode induction, Wnt signalling is required for specification and maintenance of the otic placode, and dorsal patterning of the otic vesicle. However, the requirement for specific members of the Wnt gene family for otic placode and vesicle formation and their potential interaction with Fgf signalling has been poorly defined. Due to its spatiotemporal expression during placode formation in the hindbrain Wnt8a has been postulated as a potential candidate for its specification. Here we have examined the role of Wnt8a during formation of the otic placode and vesicle in mouse embryos. Wnt8a expression depends on the presence of Fgf3 indicating a serial regulation between Fgf and Wnt signalling during otic placode induction and specification. Wnt8a by itself however is neither essential for placode specification nor redundantly required together with Fgfs for otic placode and vesicle formation. Interestingly however, Wnt8a and Fgf3 are redundantly required for expression of Fgf15 in the hindbrain indicating additional reciprocal interactions between Fgf and Wnt signalling. Further reduction of Wnt signalling by the inactivation of Wnt1 in a Wnt8a mutant background revealed a redundant requirement for both genes during morphogenesis of the dorsal portion of the otic vesicle. 相似文献
48.
Velemir Ninkovic Iris Dahlin Andja Vucetic Olivera Petrovic-Obradovic Robert Glinwood Ben Webster 《PloS one》2013,8(7)
Changes in plant volatile emission can be induced by exposure to volatiles from neighbouring insect-attacked plants. However, plants are also exposed to volatiles from unattacked neighbours, and the consequences of this have not been explored. We investigated whether volatile exchange between undamaged plants affects volatile emission and plant-insect interaction. Consistently greater quantities of two terpenoids were found in the headspace of potato previously exposed to volatiles from undamaged onion plants identified by mass spectrometry. Using live plants and synthetic blends mimicking exposed and unexposed potato, we tested the olfactory response of winged aphids, Myzus persicae. The altered potato volatile profile deterred aphids in laboratory experiments. Further, we show that growing potato together with onion in the field reduces the abundance of winged, host-seeking aphids. Our study broadens the ecological significance of the phenomenon; volatiles carry not only information on whether or not neighbouring plants are under attack, but also information on the emitter plants themselves. In this way responding plants could obtain information on whether the neighbouring plant is a competitive threat and can accordingly adjust their growth towards it. We interpret this as a response in the process of adaptation towards neighbouring plants. Furthermore, these physiological changes in the responding plants have significant ecological impact, as behaviour of aphids was affected. Since herbivore host plants are potentially under constant exposure to these volatiles, our study has major implications for the understanding of how mechanisms within plant communities affect insects. This knowledge could be used to improve plant protection and increase scientific understanding of communication between plants and its impact on other organisms. 相似文献
49.
Huifang Hao Yutaka Maeda Takuya Fukazawa Tomoki Yamatsuji Munenori Takaoka Xiao-Hong Bao Junji Matsuoka Tatsuo Okui Tsuyoshi Shimo Nagio Takigawa Yasuko Tomono Motowo Nakajima Iris M. Fink-Baldauf Sandra Nelson William Seibel Ruben Papoian Jeffrey A. Whitsett Yoshio Naomoto 《PloS one》2013,8(8)
Midkine (MDK) is a heparin-binding growth factor that is highly expressed in many malignant tumors, including lung cancers. MDK activates the PI3K pathway and induces anti-apoptotic activity, in turn enhancing the survival of tumors. Therefore, the inhibition of MDK is considered a potential strategy for cancer therapy. In the present study, we demonstrate a novel small molecule compound (iMDK) that targets MDK. iMDK inhibited the cell growth of MDK-positive H441 lung adenocarcinoma cells that harbor an oncogenic KRAS mutation and H520 squamous cell lung cancer cells, both of which are types of untreatable lung cancer. However, iMDK did not reduce the cell viability of MDK-negative A549 lung adenocarcinoma cells or normal human lung fibroblast (NHLF) cells indicating its specificity. iMDK suppressed the endogenous expression of MDK but not that of other growth factors such as PTN or VEGF. iMDK suppressed the growth of H441 cells by inhibiting the PI3K pathway and inducing apoptosis. Systemic administration of iMDK significantly inhibited tumor growth in a xenograft mouse model in vivo. Inhibition of MDK with iMDK provides a potential therapeutic approach for the treatment of lung cancers that are driven by MDK. 相似文献
50.
The extent of whole‐genome copy number alterations predicts aggressive features in primary melanomas
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Greta Gandolfi Caterina Longo Elvira Moscarella Iris Zalaudek Valentina Sancisi Margherita Raucci Gloria Manzotti Mila Gugnoni Simonetta Piana Giuseppe Argenziano Alessia Ciarrocchi 《Pigment cell & melanoma research》2016,29(2):163-175
Recent evidence indicates that melanoma comprises distinct types of tumors and suggests that specific morphological features may help predict its clinical behavior. Using a SNP‐array approach, we quantified chromosomal copy number alterations (CNA) across the whole genome in 41 primary melanomas and found a high degree of heterogeneity in their genomic asset. Association analysis correlating the number and relative length of CNA with clinical, morphological, and dermoscopic attributes of melanoma revealed that features of aggressiveness were strongly linked to the overall amount of genomic damage. Furthermore, we observed that melanoma progression and survival were mainly affected by a low number of large chromosome losses and a high number of small gains. We identified the alterations most frequently associated with aggressive melanoma, and by integrating our data with publicly available gene expression profiles, we identified five genes which expression was found to be necessary for melanoma cells proliferation. In conclusion, this work provides new evidence that the phenotypic heterogeneity of melanoma reflects a parallel genetic diversity and lays the basis to define novel strategies for a more precise prognostic stratification of patients. 相似文献