National Center for Biological science
National Center for Biological science
National Center For Biological Science | Date: 2014-04-15
The present disclosure relates to a nucleic acid based sensor, comprising a sensing 5 module, a normalizing module and a targeting module. It also relates to a method of obtaining and targeting the sensor and its use to identify and optionally quantify a target in a specific cellular microenvironment.
Ghosh S.,National Center for Biological science |
Rao Laxmi T.,National Institute of Mental Health and Neuro Sciences |
Chattarji S.,National Center for Biological science
Journal of Neuroscience | Year: 2013
The cellular and molecular effects of stress on the amygdala are strikingly different compared with those in the hippocampus. Previous findings on stress-induced plasticity were based primarily on postmortem analysis within individual areas. However, little is known about how stress affects dynamic changes and interactions in neuronal activity between the two areas. Hence, we simultaneously monitored in vivo activity of neuronal populations located in hippocampal areas CA1 and CA3 and the lateral amygdala (LA) in rats during and after chronic immobilization stress. The amplitude of auditory-evoked potentials (AEPs) in the hippocampus increased transiently only after a single 2 h stress but not when it was repeated for 10 d. In contrast, both acute and chronic stress caused a persistent increase in AEPs in the LA. Chronic stress also elicited a sustained increase in the LA but a decrease in the hippocampus in the evoked power of gamma and beta frequencies. Moreover, beta and gamma synchrony was reduced between areas CA1 and CA3 but enhanced between the LA and hippocampus after chronic stress. Granger causality spectra revealed a strong directional influence from the LA to area CA1 that persisted throughout and even 10 d after chronic stress. However, directional coupling from hippocampal area CA3 to CA1 became weaker at the end of chronic stress. Thus, our findings suggest that the growing dominance of amygdalar activity over the hippocampus during and even after chronic stress may contribute to the enhanced emotional symptoms, alongside impaired cognitive function, seen in stress-related psychiatric disorders. © 2013 the authors.
Agashe D.,National Center for Biological science
PLoS Biology | Year: 2017
Organisms often encounter stressful conditions, some of which damage their DNA. In response, some organisms show a high expression of error-prone DNA repair machinery, causing a temporary increase in the genome-wide mutation rate. Although we now have a detailed map of the molecular mechanisms underlying such stress-induced mutagenesis (SIM), it has been hotly debated whether SIM alters evolutionary dynamics. Key to this controversy is our poor understanding about which stresses increase mutagenesis and their long-term consequences for adaptation. In a new study with Escherichia coli, Maharjan and Ferenci show that while only some nutritional stresses (phosphorous and carbon limitation) increase total mutation rates, each stress generates a unique spectrum of mutations. Their results suggest the potential for specific stresses to shape evolutionary dynamics and highlight the necessity for explicit tests of the long-term evolutionary impacts of SIM. © 2017 Deepa Agashe.
Ramaswami M.,Trinity College Dublin |
Ramaswami M.,National Center for Biological science
Neuron | Year: 2014
The ability of organisms to seamlessly ignore familiar, inconsequential stimuli improves their selective attention and response to salient features of the environment. Here, I propose that this fundamental but unexplained phenomenon substantially derives from the ability of any pattern of neural excitation to create an enhanced inhibitory (or "negative") image of itself through target-specific scaling of inhibitory inputs onto active excitatory neurons. Familiar stimuli encounter strong negative images and are therefore less likely to be transmitted to higher brain centers. Integrating historical and recent observations, the negative-image model described here provides a mechanistic framework for understanding habituation, which is connected to ideas on dynamic predictive coding. In addition, it suggests insights for understanding autism spectrum disorders. Video Abstract: Neural mechanisms to filter predicted or irrelevant stimuli are essential for normal cognitive function. In this Perspective, Ramaswami synthesizes observations from multiple subfields of neuroscience to propose a role for inhibitory potentiation in adaptive filtering, behavioral habituation, and related phenomena. © 2014 Elsevier Inc.
Suvrathan A.,National Center for Biological science |
Chattarji S.,National Center for Biological science
Current Opinion in Neurobiology | Year: 2011
Fragile X syndrome (FXS) is the most commonly inherited form of mental impairment and autism. Current understanding of the molecular and cellular mechanisms underlying FXS symptoms is derived mainly from studies on the hippocampus and cortex. However, FXS is also associated with strong emotional symptoms, which are likely to involve changes in the amygdala. Unfortunately, the synaptic basis of amygdalar dysfunction in FXS remains largely unexplored. Here we describe recent findings from mouse models of FXS that have identified synaptic defects in the basolateral amygdala that are in many respects distinct from those reported earlier in the hippocampus. Long-term potentiation and surface expression of AMPA-receptors are impaired. Further, presynaptic defects are seen at both excitatory and inhibitory synapses. Remarkably, some of these synaptic defects in the amygdala are also amenable to pharmacological rescue. These results also underscore the need to modify the current hippocampus-centric framework to better explain FXS-related synaptic dysfunction in the amygdala. © 2011 Elsevier Ltd.
Krishnan Y.,National Center for Biological science |
Bathe M.,Massachusetts Institute of Technology
Trends in Cell Biology | Year: 2012
Recent advances in nucleic acid sequencing, structural, and computational technologies have resulted in dramatic progress in our understanding of nucleic acid structure and function in the cell. This knowledge, together with the predictable base-pairing of nucleic acids and powerful synthesis and expression capabilities now offers the unique ability to program nucleic acids to form precise 3D architectures with diverse applications in synthetic and cell biology. The unique modularity of structural motifs that include aptamers, DNAzymes, and ribozymes, together with their well-defined construction rules, enables the synthesis of functional higher-order nucleic acid complexes from these subcomponents. As we illustrate here, these highly programmable, smart complexes are increasingly enabling researchers to probe and program the cell in a sophisticated manner that moves well beyond the use of nucleic acids for conventional genetic manipulation alone. © 2012 Elsevier Ltd.
Saha S.,National Center for Biological science
Nature Nanotechnology | Year: 2015
The concentration of chloride ions in the cytoplasm and subcellular organelles of living cells spans a wide range (5–130 mM), and is tightly regulated by intracellular chloride channels or transporters. Chloride-sensitive protein reporters have been used to study the role of these chloride regulators, but they are limited to a small range of chloride concentrations and are pH-sensitive. Here, we show that a DNA nanodevice can precisely measure the activity and location of subcellular chloride channels and transporters in living cells in a pH-independent manner. The DNA nanodevice, called Clensor, is composed of sensing, normalizing and targeting modules, and is designed to localize within organelles along the endolysosomal pathway. It allows fluorescent, ratiometric sensing of chloride ions across the entire physiological regime. We used Clensor to quantitate the resting chloride concentration in the lumen of acidic organelles in Drosophila melanogaster. We showed that lumenal lysosomal chloride, which is implicated in various lysosomal storage diseases, is regulated by the intracellular chloride transporter DmClC-b. © 2015 Nature Publishing Group
Mayor S.,National Center for Biological science
Cell | Year: 2011
Caveolae are protein-driven membrane invaginations that regulate both the physical and chemical composition of the plasma membrane. Sinha et al. (2011) now show that caveolae are membrane reservoirs that are used to rapidly buffer against changes in membrane tension. © 2011 Elsevier Inc.
Bhalla U.S.,National Center for Biological science
Current Opinion in Neurobiology | Year: 2014
Neurons perform far more computations than the conventional framework of summation and propagation of electrical signals from dendrite to soma to axon. There is an enormous and largely hidden layer of molecular computation, and many aspects of neuronal plasticity have been modeled in chemical terms. Memorable events impinge on a neuron as special input patterns, and the neuron has to decide if it should 'remember' this event. This pattern-decoding decision is mediated by kinase cascades and signaling networks over millisecond to hour-long timescales. The process of cellular memory itself is rooted in molecular changes that give rise to life-long, stable physiological changes. Modeling studies show how cascades of synaptic molecular switches can achieve this, despite stochasticity and molecular turnover. Such biochemically detailed models form a valuable conceptual framework to assimilate the complexities of chemical signaling in neuronal computation. © 2013 .
National Center For Biological Science | Date: 2015-09-16
Disclosed are nucleic acid-based molecular switches that respond to changes in pH. The switches may be used in DNA nanodevices. The switches may also act as sensors for measuring the pH of a sample, including cells, regions thereof, and whole organisms. The switch includes an A-motif that forms at acidic pH. Also disclosed are compositions and methods for measuring the pH of cells or regions thereof, such as vesicles, the nucleus, mitochondrial matrix, or the Golgi lumen.