Recent studies suggest the hypothesis that a shared neural ensemble may link distinct memories encoded close in time1–13. According to the memory allocation hypothesis1,2, learning triggers a temporary increase in neuronal excitability14–16 that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Accordingly, we report that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week. Multiple convergent findings indicate that this overlap of neuronal ensembles links two contextual memories. First, fear paired with one context is transferred to a neutral context when the two are acquired within a day but not across a week. Second, the first memory strengthens the second memory within a day but not across a week. Older mice, known to have lower CA1 excitability16,17, do not show the overlap between ensembles, the transfer of fear between contexts, or the strengthening of the second memory. Finally, in aged animals, increasing cellular excitability and activating a common ensemble of CA1 neurons during two distinct context exposures rescued the deficit in linking memories. Taken together, these findings demonstrate that contextual memories encoded close in time are linked by directing storage into overlapping ensembles. Alteration of these processes by aging could affect the temporal structure of memories, thus impairing efficient recall of related information.
Both arylsulfonyl and alkylsulfonyl azides can be effectively activated by the cobalt(II) complexes of D 2symmetric chiral amidoporphyrins for enantioselective radical 1,5-C−H amination to stereoselectively construct 5-membered cyclic sulfonamides. In addition to C−H bonds with varied electronic properties, the Co(II)-based metalloradical system features chemoselective amination of allylic C−H bonds and is compatible with heteroaryl groups, producing functionalized 5membered chiral cyclic sulfonamides in high yields with high enantioselectivities. The unique profile of reactivity and selectivity of the Co(II)-catalyzed C−H amination is attributed to its underlying stepwise radical mechanism, which is supported by several lines of experimental evidence.
PurposeWe evaluated the concordance between core needle biopsy (CNB) and surgical specimens on examining intrinsic biological subtypes and receptor status, and determined the accuracy of CNB as a basic diagnostic method.MethodsWe analyzed breast cancer patients with paired CNB and surgical specimen samples during 2014. We used monoclonal antibodies for nuclear staining, and estrogen receptor (ER) and progesterone receptor (PR) status evaluation. A positive test was defined as staining greater than or equal to 1% of tumor cells. Human epidermal growth factor receptor 2 (HER2) was graded by immunohistochemistry and scored as 0 to 3+ according to the recommendations of the American Society of Clinical Oncology/College of American Pathologists. Ki-67 immunostaining was performed using the monoclonal antibody Ki-67, and the results were divided at 10% intervals. The cutoff value for high Ki-67 was defined as 20%. Concordance analysis of ER, PR, HER2, Ki-67, and five intrinsic biological subtypes was performed on CNB and surgical specimens. Statistical analysis for concordance was calculated using κ-tests.ResultsWe found very good agreement for ER and PR with a concordance of 96.7% for ER (κ=0.903), and 94.3% for PR (κ=0.870). HER2 and Ki-67 showed concordance rates of 84.8% (κ=0.684) and 83.5% (κ=0.647), respectively, which were interpreted as good agreement. Five subgroups analysis showed 85.8% agreement and κ-value of 0.786, also indicating good agreement.ConclusionCNB showed high diagnostic accuracy compared with surgical specimens, and good agreement for ER, PR, HER2, and Ki-67. Our findings reaffirmed the recommendation of CNB as an initial procedure for breast cancer diagnosis, and the assessment of receptor status and intrinsic biological subtypes to determine further treatment plans.
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