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light sense [keywords]
- Contorted Polycyclic Aromatics. [JOURNAL ARTICLE]
- Acc Chem Res 2014 Dec 19.
Conspectus This Account describes a body of research in the design, synthesis, and assembly of molecular materials made from strained polycyclic aromatic molecules. The strain in the molecular subunits severely distorts the aromatic molecules away from planarity. We coined the term "contorted aromatics" to describe this class of molecules. Using these molecules, we demonstrate that the curved pi-surfaces are useful as subunits to make self-assembled electronic materials. We have created and continue to study two broad classes of these "contorted aromatics": discs and ribbons. The figure that accompanies this conspectus displays the three-dimensional surfaces of a selection of these "contorted aromatics". The disc-shaped contorted molecules have well-defined conformations that create concave pi-surfaces. When these disc-shaped molecules are substituted with hydrocarbon side chains, they self-assemble into columnar superstructures. Depending on the hydrocarbon substitution, they form either liquid crystalline films or macroscopic cables. In both cases, the columnar structures are photoconductive and form p-type, hole- transporting materials in field effect transistor devices. This columnar motif is robust, allowing us to form monolayers of these columns attached to the surface of dielectrics such as silicon oxide. We use ultrathin point contacts made from individual single-walled carbon nanotubes that are separated by a few nanometers to probe the electronic properties of short stacks of a few contorted discs. We find that these materials have high mobility and can sense electron-deficient aromatic molecules. The concave surfaces of these disc-shaped contorted molecules form ideal receptors for the molecular recognition and assembly with spherical molecules such as fullerenes. These interfaces resemble ball-and-socket joints, where the fullerene nests itself in the concave surface of the contorted disc. The tightness of the binding between the two partners can be increased by creating more hemispherically shaped contorted molecules. Given the electronic structure of these contorted discs and the fullerenes, this junction is a molecular version of a p-n junction. These ball-and-socket interfaces are ideal for photoinduced charge separation. Photovoltaic devices containing these molecular recognition elements demonstrate approximately two orders of magnitude increase in charge separation. The ribbon-shaped, contorted molecules can be conceptualized as ultranarrow pieces of graphene. The contortion causes them to wind into helical ribbons. These ribbons can be formed into the active layer of field effect transistors. We substitute the ribbons with di-imides and therefore are able to transport electrons. Furthermore, these materials absorb light strongly and have ideal energetic alignment of their orbitals with conventional p-type electronic polymers. In solar cells, these contorted ribbons with commercial donor polymers have record efficiencies for non-fullerene-based solar cells. An area of interest for future exploration is the merger of these highly efficient contorted ribbons with the well-defined interfaces of the ball-and-socket materials.
- Morphologic and physiologic retinal degeneration induced by intravenous delivery of vitamin A dimers in the leporid retina. [JOURNAL ARTICLE]
- Dis Model Mech 2014 Dec 12.
The eye uses vitamin A as a cofactor to sense light, during this process a fraction of vitamin A dimerizes forming vitamin A dimers. A striking chemical signature of retinas undergoing degeneration in major eye diseases such as age-related macular degeneration (AMD) and Stargardt disease, is the accumulation of these dimers in the retinal pigment epithelium (RPE) and Bruch's membrane (BM). However, it is not known whether dimers of vitamin A are merely secondary symptoms or primary insults that drive degeneration. Here, we present a chromatography free method to prepare gram quantities of the vitamin A dimer, A2E, and show that intravenous administration of A2E to the rabbit results in retinal degeneration. A2E damaged photoreceptors and RPE cells, triggered inflammation, induced remolding of the choroidal vasculature, and triggered a decline in the retina's response to light. Data suggest that vitamin A dimers are not bystanders, but can be primary drivers of retinal degeneration. Thus, preventing dimer formation could be a preemptive strategy to address serious forms of blindness.
- Quantification of riboflavin, flavin mononucleotide and flavin adenine dinucleotide in mammalian model cells by CE with LED-induced fluorescence detection. [JOURNAL ARTICLE]
- Electrophoresis 2014 Dec 8.
Cultured mammalian cells are model systems in basic biology research, production platforms of proteins for medical use, and testbeds in synthetic biology. Flavin cofactors, in particular flavin mononucleotide and flavin adenine dinucleotide, are critical for cellular redox reactions and sense light in naturally-occurring photoreceptors and optogenetic tools. Here, we quantified flavin contents of commonly used mammalian cell lines. We compared three procedures for extraction of free and non-covalently protein-bound flavins and verified successful extraction using fluorescence spectroscopy. For separation, two CE methods with different BGEs were established and detection was performed by LED-induced fluorescence resulting in low detection limits (LODs 0.5 to 3.8 nM). Riboflavin, flavin mononucleotide and flavin adenine dinucleotide contents varied significantly between cell lines. Riboflavin (3.1 to 14 amol/cell) and flavin adenine dinucleotide (2.2 to 17.0 amol/cell) were predominant flavins, while flavin mononucleotide (0.46 to 3.4 amol/cell) was found at markedly lower levels. Observed flavin contents agree with those previously extracted from mammalian tissues, yet reduced forms of riboflavin were detected that were previously not described in tissues. Quantification of flavins in mammalian cell lines may allow a better understanding of cellular redox reactions and optogenetic tools. This article is protected by copyright. All rights reserved.
- The complete mitochondrial genome of the hybrid of Megalobrama amblycephala (♀) × Megalobrama terminalis (♂). [JOURNAL ARTICLE]
- Mitochondrial DNA 2014 Dec 8.:1-2.
Abstract In this study, we determined the complete mitochondrial DNA sequence of the hybrid of Megalobrama amblycephala (♀) × Megalobrama terminalis (♂) for the first time. The complete mitochondrial genome of the hybrid bream was sequenced to be 16,623 bp in size in accordance with the female parent, M. amblycephala. The genome contained 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 2 main non-coding regions (the control region and the origin of the light strand replication). Sequence alignment between the mitochondrial genomes of the hybrid and its female parent showed that a total of 23 mutation sites were found in 10 genes or regions, in particular, six sense mutations in four protein-coding genes (including COX1, ATP6, ND6 and Cytb). The genome information presented here may play an important role in further study on the genetic mechanisms of mitochondrial DNA in hybrids.
- Shedding light on the chloroplast as a remote control of nuclear gene expression. [JOURNAL ARTICLE]
- Plant Signal Behav 2014 Oct 31.:0.
Abstract Plants rely on a sophisticated light sensing and signaling system that allows them to respond to environmental changes. Photosensory protein systems -phytochromes, cryptochromes, phototropins, and ultraviolet (UV)-B photoreceptors- have evolved to let plants monitor light conditions and regulate different levels of gene expression and developmental processes. However, even though photoreceptor proteins are best characterized and deeply studied, it is also known that chloroplasts are able to sense light conditions and communicate the variations to the nucleus that adjust its transcriptome to the changing environment. The redox state of components of the photosynthetic electron transport chain works as a sensor of photosynthetic activity and can affect nuclear gene expression by a retrograde signaling pathway. Recently, our group showed that a retrograde signaling pathway can modulate the alternative splicing process, revealing a novel layer of gene expression control by chloroplast retrograde signaling.
- Modulation of Physical Activity to Optimize Pain Sensation following an Intra-Articular Corticosteroid Injection in Patients with Knee Osteoarthritis. [Journal Article]
- ScientificWorldJournal 2014.:209165.
Background.Intra-articular corticosteroid injection is often used to relieve pain caused by knee osteoarthritis. This study aims to assess the impact after an intra-articular corticosteroid injection treatment on objective and subjective measurement of physical function in knee osteoarthritis patients. Methods. Fourteen patients with unilateral knee osteoarthritis participated in this open-label uncontrolled trial. The intra-articular corticosteroid injection was given at the end of the second week. Physical activity was objectively measured by an accelerometer worn by the participants for eight weeks. Symptoms, quality of life and spatiotemporal parameters of gait were assessed every two weeks.
Results.From the injection until six weeks later, pain and stiffness were reduced by approximately 60%. Patients' daily physical activity time was significantly improved after injection: participation in light and moderate physical activities increased during four and two weeks, respectively.
Conclusions.The beneficial effects after the intra-articular corticosteroid injection are visible in the duration and intensity of the knee osteoarthritis patients' daily physical activity. However, these effects declined gradually two weeks after injection. Modulating the intensity and duration of physical activity would allow patients to optimize pain sensation over a longer period following an intra-articular corticosteroid injection. Trial Registration. This trial was registered with ClinicalTrials: NCT02049879.
- Piezo2 is the major transducer of mechanical forces for touch sensation in mice. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- Nature 2014 Dec 4; 516(7529):121-5.
The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals. It is postulated that mechanically activated cation channels initiate touch sensation, but the identity of these molecules in mammals has been elusive. Piezo2 is a rapidly adapting, mechanically activated ion channel expressed in a subset of sensory neurons of the dorsal root ganglion and in cutaneous mechanoreceptors known as Merkel-cell-neurite complexes. It has been demonstrated that Merkel cells have a role in vertebrate mechanosensation using Piezo2, particularly in shaping the type of current sent by the innervating sensory neuron; however, major aspects of touch sensation remain intact without Merkel cell activity. Here we show that mice lacking Piezo2 in both adult sensory neurons and Merkel cells exhibit a profound loss of touch sensation. We precisely localize Piezo2 to the peripheral endings of a broad range of low-threshold mechanoreceptors that innervate both hairy and glabrous skin. Most rapidly adapting, mechanically activated currents in dorsal root ganglion neuronal cultures are absent in Piezo2 conditional knockout mice, and ex vivo skin nerve preparation studies show that the mechanosensitivity of low-threshold mechanoreceptors strongly depends on Piezo2. This cellular phenotype correlates with an unprecedented behavioural phenotype: an almost complete deficit in light-touch sensation in multiple behavioural assays, without affecting other somatosensory functions. Our results highlight that a single ion channel that displays rapidly adapting, mechanically activated currents in vitro is responsible for the mechanosensitivity of most low-threshold mechanoreceptor subtypes involved in innocuous touch sensation. Notably, we find that touch and pain sensation are separable, suggesting that as-yet-unknown mechanically activated ion channel(s) must account for noxious (painful) mechanosensation.
- Natural photoreceptors and their application to synthetic biology. [REVIEW]
- Trends Biotechnol 2014 Nov 12.
The ability to perturb living systems is essential to understand how cells sense, integrate, and exchange information, to comprehend how pathologic changes in these processes relate to disease, and to provide insights into therapeutic points of intervention. Several molecular technologies based on natural photoreceptor systems have been pioneered that allow distinct cellular signaling pathways to be modulated with light in a temporally and spatially precise manner. In this review, we describe and discuss the underlying design principles of natural photoreceptors that have emerged as fundamental for the rational design and implementation of synthetic light-controlled signaling systems. Furthermore, we examine the unique challenges that synthetic protein technologies face when applied to the study of neural dynamics at the cellular and network level.
- Passivity analysis for memristor-based recurrent neural networks with discrete and distributed delays. [JOURNAL ARTICLE]
- Neural Netw 2014 Oct 30.:49-58.
In this paper, based on the knowledge of memristor and recurrent neural networks (RNNs), the model of the memristor-based RNNs with discrete and distributed delays is established. By constructing proper Lyapunov functionals and using inequality technique, several sufficient conditions are given to ensure the passivity of the memristor-based RNNs with discrete and distributed delays in the sense of Filippov solutions. The passivity conditions here are presented in terms of linear matrix inequalities, which can be easily solved by using Matlab Tools. In addition, the results of this paper complement and extend the earlier publications. Finally, numerical simulations are employed to illustrate the effectiveness of the obtained results.
- LIGHT/TNFSF14 increases osteoclastogenesis and decreases osteoblastogenesis in multiple myeloma-bone disease. [JOURNAL ARTICLE]
- Oncotarget 2014 Nov 12.
LIGHT, a TNF superfamily member, is involved in T-cell homeostasis and erosive bone disease associated with rheumatoid arthritis. Herein, we investigated whether LIGHT has a role in Multiple Myeloma (MM)-bone disease. We found that LIGHT was overproduced by CD14+ monocytes, CD8+ T-cells and neutrophils of peripheral blood and bone marrow (BM) from MM-bone disease patients. We also found that LIGHT induced osteoclastogenesis and inhibited osteoblastogenesis. In cultures from healthy-donors, LIGHT induced osteoclastogenesis in RANKL-dependent and -independent manners. In the presence of a sub-optimal RANKL concentration, LIGHT and RANKL synergically stimulated osteoclast formation, through the phosphorylation of Akt, NFκB and JNK pathways. In cultures of BM samples from patients with bone disease, LIGHT inhibited the formation of CFU-F and CFU-OB as well as the expression of osteoblastic markers including collagen-I, osteocalcin and bone sialoprotein-II. LIGHT indirectly inhibited osteoblastogenesis in part through sclerostin expressed by monocytes. In conclusion, our findings for the first time provide evidence for a role of LIGHT in MM-bone disease development.