Institution
Cold Spring Harbor Laboratory
Nonprofit•Cold Spring Harbor, New York, United States•
About: Cold Spring Harbor Laboratory is a nonprofit organization based out in Cold Spring Harbor, New York, United States. It is known for research contribution in the topics: Gene & Genome. The organization has 3772 authors who have published 6603 publications receiving 1010873 citations. The organization is also known as: CSHL.
Papers published on a yearly basis
Papers
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TL;DR: Exome sequencing of 343 families, each with a single child on the autism spectrum and at least one unaffected sibling, reveals de novo small indels and point substitutions, which suggest FMRP-associated genes are especially dosage-sensitive targets of cognitive disorders.
1,354 citations
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TL;DR: The current understanding of p53 illustrates how apoptosis can be integrated into a larger tumor suppressor network controlled by different signals, environmental factors, and cell type.
Abstract: The p53 tumor suppressor acts to integrate multiple stress signals into a series of diverse antiproliferative responses. One of the most important p53 functions is its ability to activate apoptosis, and disruption of this process can promote tumor progression and chemoresistance. p53 apparently promotes apoptosis through transcription-dependent and -independent mechanisms that act in concert to ensure that the cell death program proceeds efficiently. Moreover, the apoptotic activity of p53 is tightly controlled, and is influenced by a series of quantitative and qualitative events that influence the outcome of p53 activation. Interestingly, other p53 family members can also promote apoptosis, either in parallel or in concert with p53. Although incomplete, our current understanding of p53 illustrates how apoptosis can be integrated into a larger tumor suppressor network controlled by different signals, environmental factors, and cell type. Understanding this network in more detail will provide insights into cancer and other diseases, and will identify strategies to improve their therapeutic treatment.
1,344 citations
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Cornell University1, United States Department of Agriculture2, North Carolina State University3, University of Missouri4, University of Wisconsin-Madison5, Monsanto6, Beijing Normal University7, University of Illinois at Urbana–Champaign8, Purdue University9, Spanish National Research Council10, International Maize and Wheat Improvement Center11, Cold Spring Harbor Laboratory12, Kansas State University13
TL;DR: A simple additive model accurately predicts flowering time for maize, in contrast to the genetic architecture observed in the selfing plant species rice and Arabidopsis.
Abstract: Flowering time is a complex trait that controls adaptation of plants to their local environment in the outcrossing species Zea mays (maize). We dissected variation for flowering time with a set of 5000 recombinant inbred lines (maize Nested Association Mapping population, NAM). Nearly a million plants were assayed in eight environments but showed no evidence for any single large-effect quantitative trait loci (QTLs). Instead, we identified evidence for numerous small-effect QTLs shared among families; however, allelic effects differ across founder lines. We identified no individual QTLs at which allelic effects are determined by geographic origin or large effects for epistasis or environmental interactions. Thus, a simple additive model accurately predicts flowering time for maize, in contrast to the genetic architecture observed in the selfing plant species rice and Arabidopsis.
1,342 citations
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TL;DR: A loss-of-function model unravels the active function of MALAT1 as a regulator of gene expression governing hallmarks of lung cancer metastasis with this ncRNA serving as both predictive marker and therapeutic target.
Abstract: The long non-coding RNA MALAT1, also known as MALAT-1 or NEAT2, is a highly conserved nuclear ncRNA and a predictive marker for metastasis development in lung cancer. To uncover its functional importance, we developed a MALAT1 knockout model in human lung tumor cells by genomically integrating RNA destabilizing elements using Zinc Finger Nucleases. The achieved 1000-fold MALAT1 silencing provides a unique loss-of-function model. Proposed mechanisms of action include regulation of splicing or gene expression. In lung cancer, MALAT1 does not alter alternative splicing but actively regulates gene expression including a set of metastasis-associated genes. Consequently, MALAT1-deficient cells are impaired in migration and form fewer tumor nodules in a mouse xenograft. Antisense oligonucleotides blocking MALAT1 prevent metastasis formation after tumor implantation. Thus, targeting MALAT1 with antisense oligonucleotides provides a potential therapeutic approach to prevent lung cancer metastasis with MALAT1 serving as both, predictive marker and therapeutic target. Lastly, regulating gene expression, but not alternative splicing is the critical function of MALAT1 in lung cancer metastasis. In summary, ten years after the discovery of the lncRNA MALAT1 as a biomarker for lung cancer metastasis, our loss-of-function model unravels the active function of MALAT1 as a regulator of gene expression governing hallmarks of lung cancer metastasis.
1,342 citations
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TL;DR: Although inhibition is typically as strong as excitation, it is not necessary to establish tuning, even in the receptive field surround, and Balanced inhibition might serve to increase the temporal precision and thereby reduce the randomness of cortical operation, rather than to increase noise as has been proposed previously.
Abstract: Neurons in the primary auditory cortex are tuned to the intensity and specific frequencies of sounds, but the synaptic mechanisms underlying this tuning remain uncertain. Inhibition seems to have a functional role in the formation of cortical receptive fields, because stimuli often suppress similar or neighbouring responses, and pharmacological blockade of inhibition broadens tuning curves. Here we use whole-cell recordings in vivo to disentangle the roles of excitatory and inhibitory activity in the tone-evoked responses of single neurons in the auditory cortex. The excitatory and inhibitory receptive fields cover almost exactly the same areas, in contrast to the predictions of classical lateral inhibition models. Thus, although inhibition is typically as strong as excitation, it is not necessary to establish tuning, even in the receptive field surround. However, inhibition and excitation occurred in a precise and stereotyped temporal sequence: an initial barrage of excitatory input was rapidly quenched by inhibition, truncating the spiking response within a few (1-4) milliseconds. Balanced inhibition might thus serve to increase the temporal precision and thereby reduce the randomness of cortical operation, rather than to increase noise as has been proposed previously.
1,341 citations
Authors
Showing all 3800 results
Name | H-index | Papers | Citations |
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Phillip A. Sharp | 172 | 614 | 117126 |
Gregory J. Hannon | 165 | 421 | 140456 |
Ian A. Wilson | 158 | 971 | 98221 |
Marco A. Marra | 153 | 620 | 184684 |
Michael E. Greenberg | 148 | 316 | 114317 |
Tom Maniatis | 143 | 318 | 299495 |
Detlef Weigel | 142 | 516 | 84670 |
Kim Nasmyth | 142 | 294 | 59231 |
Arnold J. Levine | 139 | 485 | 116005 |
Joseph E. LeDoux | 139 | 478 | 91500 |
Gerald R. Fink | 138 | 316 | 70868 |
Ramnik J. Xavier | 138 | 597 | 101879 |
Harold E. Varmus | 137 | 496 | 76320 |
David A. Jackson | 136 | 1095 | 68352 |
Scott W. Lowe | 134 | 396 | 89376 |