376 research outputs found
Trascriptional down regulation of poly(ADP-ribose)polymerase gene expression by E1A binding to pRB proteins protects murine keratinocytes from radiation induced apoptosis.
SEOM clinical guidelines in hereditary breast and ovarian cancer (2019)
Mutations in BRCA1 and BRCA2 high penetrance genes account for most hereditary breast and ovarian cancer, although other new high-moderate penetrance genes included in multigene panels have increased the genetic diagnosis of hereditary breast and ovarian cancer families by 50%. Multigene cancer panels provide new challenges related to increased frequency of variants of uncertain significance, new gene-specific cancer risk assessments, and clinical recommendations for carriers of mutations of new genes. Although clinical criteria for genetic testing continue to be largely based on personal and family history with around a 10% detection rate, broader criteria are being applied with a lower threshold for detecting mutations when there are therapeutic implications for patients with breast or ovarian cancer. In this regard, new models of genetic counselling and testing are being implemented following the registration of PARP inhibitors for individuals who display BRCA mutations. Massive sequencing techniques in tumor tissue is also driving a paradigm shift in genetic testing and potential identification of germline mutations. In this paper, we review the current clinical criteria for genetic testing, as well as surveillance recommendations in healthy carriers, risk reduction surgical options, and new treatment strategies in breast cancer gene-mutated carriers
Axon swellings produced in vivo in isolated segments of nerves
Within 3–5 hrs after cutting rat and cat sciatic nerves into segments which had no connection with the cell body, club-shaped axon swellings were observed at both ends of the segments. The swollen portion of these axons showed increased histochemical reactions for DPN-diaphorase, lactic dehydrogenase, malic dehydrogenase, succinic dehydrogenase, and protein; the increase lasted for 24–48 hrs after the nerve was cut. The swollen axons were morphologically and histochemically similar to, but never as markedly changed, as those observed in the proximal stumps of severed nerves. The development of axon swellings was prevented by depolarization of the entire segment with KCl; however, if KCl was applied selectively to the stumps of the segment, it appeared to intensify rather than prevent the swelling. It was also noted that the extent of axon swelling was inversely proportional to the length of the segment. These observations suggested that the development and extent of axon swelling was related to the intensity of local injury currents in the tissue. Innerhalb von 3–5 Std nach Zerschneidung des Nervus ischiadicus von Ratten und Katzen in Segmente, die keine Verbindung mit dem Zellkörper besitzen, sind zylinderförmige Axonschwellungen an beiden Enden der Segmente zu beobachten. Der angeschwollene Teil dieser Axone zeigt verstärkte histochemische Reaktionen auf DPN-Diaphorase, Milchsäure-Dehydrogenase, Apfelsäure-Dehydrogenase, Bernsteinsäure-Dehydrogenase und Protein; dieser Anstieg hält 24–48 Std nach der Durchtrennung des Nervs an. Die Axonschwellungen sind sowohl morphologisch als auch histochemisch ähnlich — jedoch niemals in gleich starker Ausprägung — jenen, die in den proximalen Stümpfen von verletzten Nerven beobachtet werden.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47224/1/401_2004_Article_BF00684398.pd
Three-dimensional reconstruction of synapses and dendritic spines in the rat and ground squirrel hippocampus: New structural-functional paradigms for synaptic function
Published data are reviewed along with our own data on synaptic plasticity and rearrangements of synaptic organelles in the central nervous system. Contemporary laser scanning and confocal microscopy techniques are discussed, along with the use of serial ultrathin sections for in vivo and in vitro studies of dendritic spines, including those addressing relationships between morphological changes and the efficiency of synaptic transmission, especially in conditions of the long-term potentiation model. Different categories of dendritic spines and postsynaptic densities are analyzed, as are the roles of filopodia in originating spines. The role of serial ultrathin sections for unbiased quantitative stereological analysis and three-dimensional reconstruction is assessed. The authors data on the formation of more than two synapses on single mushroom spines on neurons in hippocampal field CA1 are discussed. Analysis of these data provides evidence for new paradigms in both the organization and functioning of synapses
Genetically-Directed, Cell Type-Specific Sparse Labeling for the Analysis of Neuronal Morphology
Background: In mammals, genetically-directed cell labeling technologies have not yet been applied to the morphologic analysis of neurons with very large and complex arbors, an application that requires extremely sparse labeling and that is only rendered practical by limiting the labeled population to one or a few predetermined neuronal subtypes. Methods and Findings: In the present study we have addressed this application by using CreER technology to noninvasively label very small numbers of neurons so that their morphologies can be fully visualized. Four lines of IRES-CreER knock-in mice were constructed to permit labeling selectively in cholinergic or catecholaminergic neurons [choline acetyltransferase (ChAT)-IRES-CreER or tyrosine hydroxylase (TH)-IRES-CreER], predominantly in projection neurons [neurofilament light chain (NFL)-IRES-CreER], or broadly in neurons and some glia [vesicle-associated membrane protein2 (VAMP2)-IRES-CreER]. When crossed to the Z/AP reporter and exposed to 4-hydroxytamoxifen in the early postnatal period, the number of neurons expressing the human placental alkaline phosphatase reporter can be reproducibly lowered to fewer than 50 per brain. Sparse Cre-mediated recombination in ChAT-IRES-CreER;Z/AP mice shows the full axonal and dendritic arbors of individual forebrain cholinergic neurons, the first time that the complete morphologies of these very large neurons have been revealed in any species. Conclusions: Sparse genetically-directed, cell type-specific neuronal labeling with IRES-creER lines should prove useful fo
Finding the engram.
Many attempts have been made to localize the physical trace of a memory, or engram, in the brain. However, until recently, engrams have remained largely elusive. In this Review, we develop four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram. Recent \u27capture\u27 studies use novel approaches to tag populations of neurons that are active during memory encoding, thereby allowing these engram-associated neurons to be manipulated at later times. We propose that findings from these capture studies represent considerable progress in allowing us to observe, erase and express the engram
Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex
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The Invariance Hypothesis Implies Domain-Specific Regions in Visual Cortex
Is visual cortex made up of general-purpose information processing machinery, or does it consist of a collection of specialized modules? If prior knowledge, acquired from learning a set of objects is only transferable to new objects that share properties with the old, then the recognition system’s optimal organization must be one containing specialized modules for different object classes. Our analysis starts from a premise we call the invariance hypothesis: that the computational goal of the ventral stream is to compute an invariant-to-transformations and discriminative signature for recognition. The key condition enabling approximate transfer of invariance without sacrificing discriminability turns out to be that the learned and novel objects transform similarly. This implies that the optimal recognition system must contain subsystems trained only with data from similarly-transforming objects and suggests a novel interpretation of domain-specific regions like the fusiform face area (FFA). Furthermore, we can define an index of transformation-compatibility, computable from videos, that can be combined with information about the statistics of natural vision to yield predictions for which object categories ought to have domain-specific regions in agreement with the available data. The result is a unifying account linking the large literature on view-based recognition with the wealth of experimental evidence concerning domain-specific regions.National Science Foundation (U.S.). Science and Technology Center (Award CCF-1231216)National Science Foundation (U.S.) (Grant NSF-0640097)National Science Foundation (U.S.) (Grant NSF-0827427)United States. Air Force Office of Scientific Research (Grant FA8650-05-C-7262)Eugene McDermott Foundatio
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