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  • 1
    Publication Date: 2018-05-04
    Description: In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision have been unclear. In this work, combining cell-based in vitro gradient reconstitution, genetic rewiring, and mathematical modeling, we systematically analyzed the distinctive architectural features of the Sonic Hedgehog pathway. We found that the combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared with alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes and to compare the patterning behaviors of alternative, rewired pathway architectures offers a powerful way to understand and engineer multicellular patterning.
    Keywords: Development, Engineering
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2012-04-12
    Description: Observations with the Venus Express magnetometer and low-energy particle detector revealed magnetic field and plasma behavior in the near-Venus wake that is symptomatic of magnetic reconnection, a process that occurs in Earth's magnetotail but is not expected in the magnetotail of a nonmagnetized planet such as Venus. On 15 May 2006, the plasma flow in this region was toward the planet, and the magnetic field component transverse to the flow was reversed. Magnetic reconnection is a plasma process that changes the topology of the magnetic field and results in energy exchange between the magnetic field and the plasma. Thus, the energetics of the Venus magnetotail resembles that of the terrestrial tail, where energy is stored and later released from the magnetic field to the plasma.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, T L -- Lu, Q M -- Baumjohann, W -- Russell, C T -- Fedorov, A -- Barabash, S -- Coates, A J -- Du, A M -- Cao, J B -- Nakamura, R -- Teh, W L -- Wang, R S -- Dou, X K -- Wang, S -- Glassmeier, K H -- Auster, H U -- Balikhin, M -- New York, N.Y. -- Science. 2012 May 4;336(6081):567-70. doi: 10.1126/science.1217013. Epub 2012 Apr 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Chinese Academy of Sciences Key Laboratory of Geospace Environment, University of Science and Technology of China, Hefei 230026, China. tielong.zhang@oeaw.ac.at〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22491094" target="_blank"〉PubMed〈/a〉
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2018-11-09
    Description: Ribonuclease P (RNase P) is a universal ribozyme responsible for processing the 5'-leader of pre–transfer RNA (pre-tRNA). Here, we report the 3.5-angstrom cryo–electron microscopy structures of Saccharomyces cerevisiae RNase P alone and in complex with pre-tRNA Phe . The protein components form a hook-shaped architecture that wraps around the RNA and stabilizes RNase P into a "measuring device" with two fixed anchors that recognize the L-shaped pre-tRNA. A universally conserved uridine nucleobase and phosphate backbone in the catalytic center together with the scissile phosphate and the O3' leaving group of pre-tRNA jointly coordinate two catalytic magnesium ions. Binding of pre-tRNA induces a conformational change in the catalytic center that is required for catalysis. Moreover, simulation analysis suggests a two-metal-ion S N 2 reaction pathway of pre-tRNA cleavage. These results not only reveal the architecture of yeast RNase P but also provide a molecular basis of how the 5'-leader of pre-tRNA is processed by eukaryotic RNase P.
    Keywords: Biochemistry, Online Only
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2018-11-29
    Description: A plethora of bacterial allosteric transcription factors (aTFs) have been identified to sense a variety of small molecules. Introduction of a novel aTF-based approach to sense diverse small molecules in vitro will signify a broad series of detection applications. Here, we found that aTFs could interact with their nicked DNA binding sites. Building from this new finding, we designed and implemented a novel aTF-based nicked DNA template–assisted signal transduction system (aTF-NAST) by using the competition between aTFs and T4 DNA ligase to bind to the nicked DNA. This aTF-NAST could reliably and modularly transduce the signal of small molecules recognized by aTFs to the ligated DNA signal, thus enabling the small molecules to be measured via various mature and robust DNA detection methods. Coupling this aTF-NAST with three DNA detection methods, we demonstrated nine novel biosensors for the detection of an antiseptic 4-hydroxybenzoic acid, a disease marker uric acid and an antibiotic tetracycline. These biosensors show impressive sensitivity and robustness in real-life analysis, highlighting the great potential of our aTF-NAST for biosensing applications.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 5
    Publication Date: 2011-08-13
    Description: We report classes of electronic systems that achieve thicknesses, effective elastic moduli, bending stiffnesses, and areal mass densities matched to the epidermis. Unlike traditional wafer-based technologies, laminating such devices onto the skin leads to conformal contact and adequate adhesion based on van der Waals interactions alone, in a manner that is mechanically invisible to the user. We describe systems incorporating electrophysiological, temperature, and strain sensors, as well as transistors, light-emitting diodes, photodetectors, radio frequency inductors, capacitors, oscillators, and rectifying diodes. Solar cells and wireless coils provide options for power supply. We used this type of technology to measure electrical activity produced by the heart, brain, and skeletal muscles and show that the resulting data contain sufficient information for an unusual type of computer game controller.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Dae-Hyeong -- Lu, Nanshu -- Ma, Rui -- Kim, Yun-Soung -- Kim, Rak-Hwan -- Wang, Shuodao -- Wu, Jian -- Won, Sang Min -- Tao, Hu -- Islam, Ahmad -- Yu, Ki Jun -- Kim, Tae-il -- Chowdhury, Raeed -- Ying, Ming -- Xu, Lizhi -- Li, Ming -- Chung, Hyun-Joong -- Keum, Hohyun -- McCormick, Martin -- Liu, Ping -- Zhang, Yong-Wei -- Omenetto, Fiorenzo G -- Huang, Yonggang -- Coleman, Todd -- Rogers, John A -- New York, N.Y. -- Science. 2011 Aug 12;333(6044):838-43. doi: 10.1126/science.1206157.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Materials Science and Engineering, Beckman Institute for Advanced Science and Technology, and Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21836009" target="_blank"〉PubMed〈/a〉
    Keywords: Adhesiveness ; Dermis ; Elastic Modulus ; Elastomers ; Electric Power Supplies ; Electrocardiography/instrumentation/methods ; Electrodes ; Electrodiagnosis/*instrumentation/*methods ; Electroencephalography/instrumentation/methods ; Electromyography/instrumentation/methods ; *Epidermis ; Humans ; Mechanical Phenomena ; Monitoring, Physiologic/*instrumentation/*methods ; Nanostructures ; *Semiconductors
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 6
    Publication Date: 2013-03-16
    Description: Recent discoveries of large leg feathers in some theropods have implications for our understanding of the evolution of integumentary features on the avialan leg, and particularly of their relevance for the origin of avialan flight. Here we report 11 basal avialan specimens that will greatly improve our knowledge of leg integumentary features among early birds. In particular, they provide solid evidence for the existence of enlarged leg feathers on a variety of basal birds, suggest that extensively scaled feet might have appeared secondarily at an early stage in ornithuromorph evolution, and demonstrate a distal-to-proximal reduction pattern for leg feathers in avialan evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zheng, Xiaoting -- Zhou, Zhonghe -- Wang, Xiaoli -- Zhang, Fucheng -- Zhang, Xiaomei -- Wang, Yan -- Wei, Guangjin -- Wang, Shuo -- Xu, Xing -- New York, N.Y. -- Science. 2013 Mar 15;339(6125):1309-12. doi: 10.1126/science.1228753.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Geology and Paleontology, Linyi University, Linyi City, Shandong, China. ty4291666@163.com〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23493711" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Birds/*anatomy & histology ; Feathers/*anatomy & histology ; *Fossils ; Hindlimb/*anatomy & histology ; Wings, Animal/*anatomy & histology
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
    Publication Date: 2018-05-25
    Description: Prion-like RNA binding proteins (RBPs) such as TDP43 and FUS are largely soluble in the nucleus but form solid pathological aggregates when mislocalized to the cytoplasm. What keeps these proteins soluble in the nucleus and promotes aggregation in the cytoplasm is still unknown. We report here that RNA critically regulates the phase behavior of prion-like RBPs. Low RNA/protein ratios promote phase separation into liquid droplets, whereas high ratios prevent droplet formation in vitro. Reduction of nuclear RNA levels or genetic ablation of RNA binding causes excessive phase separation and the formation of cytotoxic solid-like assemblies in cells. We propose that the nucleus is a buffered system in which high RNA concentrations keep RBPs soluble. Changes in RNA levels or RNA binding abilities of RBPs cause aberrant phase transitions.
    Keywords: Cell Biology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
    Publication Date: 2018-07-12
    Description: Beige adipocytes can be induced from white adipocytes and precursors upon stimulation by cold temperatures and act like brown adipocytes to increase energy expenditure. Most in vivo studies examining the mechanisms for the induction of beige adipocytes have focused on subcutaneous white adipose tissue (sWAT; benign fat) in the mouse. How intra-abdominal WAT (aWAT; malignant fat) develops into beige adipocytes remains obscure, largely because there is a lack of a good animal model for the induction of beige adipocytes from aWAT. To better understand the development of beige adipocytes from mammalian WATs, especially aWAT, we induced beige adipocytes from bat aWAT and mouse sWAT by exposure to cold temperatures and analyzed their molecular signatures. RNA sequencing followed by whole genome–wide expression analysis shows that beige adipocytes induced from bat aWAT, rather than sWAT, have molecular signatures resembling those of mouse sWAT-induced beige adipocytes and exhibit dynamic profiles similar to those of classical brown adipocytes. In addition, we identified molecular markers that were highly enriched in beige adipocytes and conserved between bat aWAT and mouse sWAT, a set that included the genes Uqcrc1 and Letm1 . Furthermore, knockdown of Uqcrc1 and Letm1 expression shows that they are required not only for beige adipocyte differentiation but also for preadipocyte maturation. This study presents a new model for research into the induction of beige adipocytes from aWAT in vivo, which, when combined with models where beige adipocytes are induced from sWAT, provides insight into therapeutic approaches for combating obesity-related diseases in humans.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 9
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    American Association for the Advancement of Science (AAAS)
    In: Science
    Publication Date: 2018-09-07
    Description: Mutations in two genes, PKD1 and PKD2 , account for most cases of autosomal dominant polycystic kidney disease, one of the most common monogenetic disorders. Here we report the 3.6-angstrom cryo–electron microscopy structure of truncated human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet noncanonical, transient receptor potential (TRP) channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular half, S6a, resembling pore helix 1 in a typical TRP channel. Three positively charged, cavity-facing residues on S6b may block cation permeation. In addition to the VGIC, a five–transmembrane helix domain and a cytosolic PLAT domain were resolved in PKD1. The PKD1-PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins.
    Keywords: Biochemistry, Online Only
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    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
    Publication Date: 2018-10-26
    Description: Clinical observations indicate that the paramedian region of the thalamus is a critical node for controlling wakefulness. However, the specific nucleus and neural circuitry for this function remain unknown. Using in vivo fiber photometry or multichannel electrophysiological recordings in mice, we found that glutamatergic neurons of the paraventricular thalamus (PVT) exhibited high activities during wakefulness. Suppression of PVT neuronal activity caused a reduction in wakefulness, whereas activation of PVT neurons induced a transition from sleep to wakefulness and an acceleration of emergence from general anesthesia. Moreover, our findings indicate that the PVT–nucleus accumbens projections and hypocretin neurons in the lateral hypothalamus to PVT glutamatergic neurons’ projections are the effector pathways for wakefulness control. These results demonstrate that the PVT is a key wakefulness-controlling nucleus in the thalamus.
    Keywords: Neuroscience
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Geosciences , Computer Science , Medicine , Natural Sciences in General , Physics
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