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light sense [keywords]
- Potential implications of the bystander effect on TCP and EUD when considering target volume dose heterogeneity. [JOURNAL ARTICLE]
- Int J Radiat Biol 2014 Jul 9.:1-21.
Abstract Purpose: In light of in vitro evidence suggesting that radiation induced bystander effects may enhance non-local cell killing, there is potential for impact on radiotherapy treatment planning paradigms such as the goal of delivering a uniform dose throughout the clinical target volume (CTV). This work applies a bystander effect model to calculate equivalent uniform dose (EUD) and tumour control probability (TCP) for external beam prostate treatment and compares the results with a more common model where local response is dictated exclusively by local absorbed dose. The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. Materials and methods: EUD and TCP of a prostate cancer target volume under conditions of increasing dose heterogeneity were calculated using two models: one incorporating bystander effects derived from previously published in vitro bystander data (McMahon et al., 2013a, McMahon et al., 2012); and one using a common linear-quadratic (LQ) response that relies exclusively on local absorbed dose. Dose through the CTV was modelled as a normal distribution, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). Also, a representative clinical dose distribution was examined as cold (low dose) sub-volumes were systematically introduced. Results: The bystander model suggests a moderate degree of dose heterogeneity throughout a target volume will yield as good or better outcome compared to a uniform dose in terms of EUD and TCP. For a typical intermediate risk prostate prescription of 78 Gy over 39 fractions maxima in EUD and TCP as a function of increasing SD occurred at SD ∼ 5 Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. Small, but potentially significant differences in the outcome metrics between the models were identified in the clinically-derived dose distribution as cold sub-volumes were introduced. Conclusions: In terms of EUD and TCP, the bystander model demonstrates the potential to deviate from the common local LQ model predictions as dose heterogeneity through a prostate CTV varies. The results suggest, at least in a limiting sense, the potential for allowing some degree of dose heterogeneity within a CTV, although further investigation of the assumptions of the bystander model are warranted.
- Field-omics-understanding large-scale molecular data from field crops. [Journal Article]
- Front Plant Sci 2014.:286.
The recent advances in gene expression analysis as well as protein and metabolite quantification enable genome-scale capturing of complex biological processes at the molecular level in crop field trials. This opens up new possibilities for understanding the molecular and environmental complexity of field-based systems and thus shedding light on the black box between genotype and environment, which in agriculture always is influenced by a multi-stress environment and includes management interventions. Nevertheless, combining different types of data obtained from the field and making biological sense out of large datasets remain challenging. Here we highlight the need to create a cross-disciplinary platform for innovative experimental design, sampling and subsequent analysis of large-scale molecular data obtained in field trials. For these reasons we put forward the term field-omics: "Field-omics strives to couple information from genomes, transcriptomes, proteomes, metabolomes and metagenomes to the long-established practice in crop science of conducting field trials as well as to adapt current strategies for recording and analysing field data to facilitate integration with '-omics' data."
- Role of the Dopaminergic System in the Development of Myopia in Children and Adolescents. [JOURNAL ARTICLE]
- J Child Neurol 2014 Jul 4.
This review summarizes the experimental evidence that supports the role of dopamine in the regulation of ocular axial growth. The most important functions attributed to dopamine are light adaptation and regulation of the retinal circadian rhythm. An increase of the retinal levels of dopamine activates D1 and D2 dopaminergic receptors present throughout the retina, generating a signal that inhibits axial growth once the eye has reached emmetropization. Researchers induced form-deprivation myopia in animal models in order to assess the different changes of ocular axial growth. Other studies have shown that phenylethylamine is an endogenous precursor-neurotransmitter capable of modulating the activity of dopamine. Considering the role of the dopaminergic system in the development of myopia (in children and adolescents) and the fact that phenylethylamine improves the consequences of a dopamine deficit, it would be interesting to study the effect of phenylethylamine on the regulation of axial growth, which represents the genesis of myopia.
- Audio-visual feedback improves the BCI performance in the navigational control of a humanoid robot. [Journal Article]
- Front Neurorobot 2014.:20.
Advancement in brain computer interfaces (BCI) technology allows people to actively interact in the world through surrogates. Controlling real humanoid robots using BCI as intuitively as we control our body represents a challenge for current research in robotics and neuroscience. In order to successfully interact with the environment the brain integrates multiple sensory cues to form a coherent representation of the world. Cognitive neuroscience studies demonstrate that multisensory integration may imply a gain with respect to a single modality and ultimately improve the overall sensorimotor performance. For example, reactivity to simultaneous visual and auditory stimuli may be higher than to the sum of the same stimuli delivered in isolation or in temporal sequence. Yet, knowledge about whether audio-visual integration may improve the control of a surrogate is meager. To explore this issue, we provided human footstep sounds as audio feedback to BCI users while controlling a humanoid robot. Participants were asked to steer their robot surrogate and perform a pick-and-place task through BCI-SSVEPs. We found that audio-visual synchrony between footsteps sound and actual humanoid's walk reduces the time required for steering the robot. Thus, auditory feedback congruent with the humanoid actions may improve motor decisions of the BCI's user and help in the feeling of control over it. Our results shed light on the possibility to increase robot's control through the combination of multisensory feedback to a BCI user.
- Spatio-temporally precise activation of engineered receptor tyrosine kinases by light. [JOURNAL ARTICLE]
- EMBO J 2014 Jul 1.
Receptor tyrosine kinases (RTKs) are a large family of cell surface receptors that sense growth factors and hormones and regulate a variety of cell behaviours in health and disease. Contactless activation of RTKs with spatial and temporal precision is currently not feasible. Here, we generated RTKs that are insensitive to endogenous ligands but can be selectively activated by low-intensity blue light. We screened light-oxygen-voltage (LOV)-sensing domains for their ability to activate RTKs by light-activated dimerization. Incorporation of LOV domains found in aureochrome photoreceptors of stramenopiles resulted in robust activation of the fibroblast growth factor receptor 1 (FGFR1), epidermal growth factor receptor (EGFR) and rearranged during transfection (RET). In human cancer and endothelial cells, light induced cellular signalling with spatial and temporal precision. Furthermore, light faithfully mimicked complex mitogenic and morphogenic cell behaviour induced by growth factors. RTKs under optical control (Opto-RTKs) provide a powerful optogenetic approach to actuate cellular signals and manipulate cell behaviour.
- The neural correlates of social connection. [JOURNAL ARTICLE]
- Cogn Affect Behav Neurosci 2014 Jul 2.
Cultivating social connection has long been a goal of psychology, philosophy, religion, and public policy. Yet the psychological and neural responses that accompany a feeling of connection to others remain unclear. In the present study, we used functional neuroimaging to shed light on the neural correlates of self- and other-focused processes during the successful self-generation of feelings of social connection. To do this, we used a trait judgment task to localize functional activation related to self-focused thought. We then examined brain responses during guided exercises designed both to encourage feeling love and connection from others (i.e., self-focused) and to generate feelings of love and connection toward others (i.e., other-focused). Our results indicated that generating feelings of social connection recruited a portion of the medial prefrontal cortex (MPFC) implicated in thinking about both the self and others. Within this larger area, we observed distinct profiles of activation within different subregions. Although rostral anterior cingulate cortex was more strongly activated by other-focused components of the task, a more dorsal portion of MPFC was comparatively more active during primarily self-focused components of the task. Somewhat surprisingly, stronger feelings of social connection were not associated with greater activation in the anterior cingulate, but rather with less activation in the dorsal region of the MPFC related to self-focused thought. These results are consistent with the possibility that reducing certain kinds of self-focused thought might yield a greater sense of social connection to and care for others.
- Engineering adenylate cyclases regulated by near-infrared window light. [JOURNAL ARTICLE]
- Proc Natl Acad Sci U S A 2014 Jun 30.
Bacteriophytochromes sense light in the near-infrared window, the spectral region where absorption by mammalian tissues is minimal, and their chromophore, biliverdin IXα, is naturally present in animal cells. These properties make bacteriophytochromes particularly attractive for optogenetic applications. However, the lack of understanding of how light-induced conformational changes control output activities has hindered engineering of bacteriophytochrome-based optogenetic tools. Many bacteriophytochromes function as homodimeric enzymes, in which light-induced conformational changes are transferred via α-helical linkers to the rigid output domains. We hypothesized that heterologous output domains requiring homodimerization can be fused to the photosensory modules of bacteriophytochromes to generate light-activated fusions. Here, we tested this hypothesis by engineering adenylate cyclases regulated by light in the near-infrared spectral window using the photosensory module of the Rhodobacter sphaeroides bacteriophytochrome BphG1 and the adenylate cyclase domain from Nostoc sp. CyaB1. We engineered several light-activated fusion proteins that differed from each other by approximately one or two α-helical turns, suggesting that positioning of the output domains in the same phase of the helix is important for light-dependent activity. Extensive mutagenesis of one of these fusions resulted in an adenylate cyclase with a sixfold photodynamic range. Additional mutagenesis produced an enzyme with a more stable photoactivated state. When expressed in cholinergic neurons in Caenorhabditis elegans, the engineered adenylate cyclase affected worm behavior in a light-dependent manner. The insights derived from this study can be applied to the engineering of other homodimeric bacteriophytochromes, which will further expand the optogenetic toolset.
- Rotation, oscillation and hydrodynamic synchronization of optically trapped oblate spheroidal microparticles. [JOURNAL ARTICLE]
- Opt Express 2014 Jun 30; 22(13):16207-16221.
While the behavior of optically trapped dielectric spherical particles has been extensively studied, the behavior of non-spherical particles remains mainly unexplored. In this work we focus on the dynamics of oblate spheroidal particles trapped in a tightly focused elliptically-polarized vortex beam. In our experiments we used polystyrene spheroids of aspect ratio of major to minor axes equal to 2.55 and of a volume equal to a sphere of diameter 1.7μm. We demonstrate that such particles can be trapped in three dimensions, with the minor axis oriented perpendicular to both the beam polarization (linear) and the beam propagation, can spin in a circularly polarized beam and an optical vortex beam around the axis parallel with the beam propagation. We also observed that these particles can exhibit a periodic motion in the plane transversal to the beam propagation. We measured that the transfer of the orbital angular momentum from the vortex beam to the spheroid gives rise to torques one order of magnitude stronger comparing to the circularly polarized Gaussian beam. We employed a phase-only spatial light modulator to generate several vortex beam traps with one spheroid in each of them. Due to independent setting of beams parameters we controlled spheroids frequency and sense of rotation and observed hydrodynamic phase and frequency locking of rotating spheroids. These optically driven spheroids offer a simple alternative approach to the former techniques based on birefringent, absorbing or chiral microrotors.
- [Preliminary analysis of bitter substances in spica of Prunella vulgaris]. [English Abstract, Journal Article]
- Zhongguo Zhong Yao Za Zhi 2014 Feb; 39(3):423-6.
Volatile oil components and the contents and types of amino acid in spica of Prunella vulgaris were analysed by GC-MS and amino acid analyzer. Esters, fatty acids, aromatic hydrocarbon, ketone and several alcohol compounds were identified by mass spectrum comparison. In these ingredients, beta-ionone smelled aroma of cedar, raspberry, nerolidol showed weak sweet soft orange blossom flavor, neroli tasted sweet and fresh, nerolidol tasted sweet with light aroma of wood, hexadecanal showed a weak aroma of flowers and wax, alpha-sinensal had rich and fresh sweet orange flavor. To some extent, these types of aromatic substances can affect the taste of herbal tea or decoction made of Spica Prunellae. Among amino acids detected, natural amino acids accounted for a larger proportion, and those natural amino acids showed bitterness, slight bitterness, sourness (freshness), sweetness, slight sweetness, sourness (slight freshness). The results indicated that bitter and slightly bitter amino acids have the greatest impacts on the sense of Spica Prunellae.
- Frontotemporal dementia and its subtypes: a genome-wide association study. [Journal Article]
- Lancet Neurol 2014 Jul; 13(7):686-99.
Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with FTD and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with FTD and 4308 controls), we did separate association analyses for each FTD subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and FTD overlapping with motor neuron disease [FTD-MND]), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10(-8)) single-nucleotide polymorphisms.We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10(-8)). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, HLA locus (immune system), for rs9268877 (p=1·05 × 10(-8); odds ratio=1·204 [95% CI 1·11-1·30]), rs9268856 (p=5·51 × 10(-9); 0·809 [0·76-0·86]) and rs1980493 (p value=1·57 × 10(-8), 0·775 [0·69-0·86]) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural FTD subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10(-7); 0·814 [0·71-0·92]). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis.Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD.The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center.