15 research outputs found
Molecular Constraints on Synaptic Tagging and Maintenance of Long-Term Potentiation: A Predictive Model
Protein synthesis-dependent, late long-term potentiation (LTP) and depression
(LTD) at glutamatergic hippocampal synapses are well characterized examples of
long-term synaptic plasticity. Persistent increased activity of the enzyme
protein kinase M (PKM) is thought essential for maintaining LTP. Additional
spatial and temporal features that govern LTP and LTD induction are embodied in
the synaptic tagging and capture (STC) and cross capture hypotheses. Only
synapses that have been "tagged" by an stimulus sufficient for LTP and learning
can "capture" PKM. A model was developed to simulate the dynamics of key
molecules required for LTP and LTD. The model concisely represents
relationships between tagging, capture, LTD, and LTP maintenance. The model
successfully simulated LTP maintained by persistent synaptic PKM, STC, LTD, and
cross capture, and makes testable predictions concerning the dynamics of PKM.
The maintenance of LTP, and consequently of at least some forms of long-term
memory, is predicted to require continual positive feedback in which PKM
enhances its own synthesis only at potentiated synapses. This feedback
underlies bistability in the activity of PKM. Second, cross capture requires
the induction of LTD to induce dendritic PKM synthesis, although this may
require tagging of a nearby synapse for LTP. The model also simulates the
effects of PKM inhibition, and makes additional predictions for the dynamics of
CaM kinases. Experiments testing the above predictions would significantly
advance the understanding of memory maintenance.Comment: v3. Minor text edits to reflect published versio
Seroprevalence and immunological memory against SARS-CoV-2 in lung cancer patients : the SOLID study
At present, we did not find any articles that studied seroprevalence and its persistence several months later in lung cancer patients in the setting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Most patients with coronavirus disease 2019 (COVID-19) go on to develop antibodies (Abs) against viral proteins. However, it is not known how long these Abs last nor whether cancer treatments could affect the duration of immune response. This prospective, longitudinal, multicenter serological study in the setting of SARS-CoV-2 infection was carried out in 50 Spanish hospitals. Eligibility criterion was the diagnosis of any lung cancer. The determination of anti-SARS-CoV-2 IgG Abs was performed by qualitative immuno-enzymatic assay using enzyme-linked immunosorbent assay (ELISA) kit from NovaLisa whose Abs target the recombinant antigen N of the nucleocapsid of SARS-CoV-2. The first Ab determination was performed between April 21 and June 3, 2020. The second Ab determination was performed in all previously seropositive patients, between September 10 and November 20, 2020. Study objectives were to prospectively determine seroprevalence in unselected lung cancer patients during the first wave of the pandemic; the persistence of immunity; protection or lack thereof against reinfection; and the influence of treatments on maintenance or loss of immunity. Of 1,500 patients, 128 were seropositive, overall prevalence of 8.5% seropositivity [95% confidence interval (CI): 7.2-10.1%]. Seventy-five percent were in active cancer treatment. Forty-seven point seven percent of IgG positive participants had experienced a symptomatic illness suspected of being infected with SARS-CoV-2 (95% CI: 38.8-56.6%). A second determination was performed on average 4.5 months later [interquartile range (IQR), 4.0-5.0 months] and obtained for 104 of the initially seropositive patients (81%), it could not be obtained in 24 patients, the majority due to death caused by disease progression (73%). In the second determination, IgG was not detected in 30.8% of patients. The severity of the infection, the need for hospitalization (P=0.032) and the presence of symptoms at diagnosis (P=0.02) were associated with persistence of immunity in the second determination. No variables or treatments received were associated with Abs loss. Immunity against SARS-CoV-2 does not appear to be compromised by treatment and persists beyond 4 months. Neither do mortality rates appear to be particularly high in this unselected population. ClinicalTrials.gov identifier: NCT04407143