Dopamine promotes cognitive effort by biasing the benefits versus costs of cognitive work.

Stimulants such as methylphenidate are increasingly used for cognitive enhancement but precise mechanisms are unknown. We found that methylphenidate boosts willingness to expend cognitive effort by altering the benefit-to-cost ratio of cognitive work. Willingness to expend effort was greater for participants with higher striatal dopamine synthesis capacity, whereas methylphenidate and sulpiride, a selective D2 receptor antagonist, increased cognitive motivation more for participants with lower synthesis capacity. A sequential sampling model informed by momentary gaze revealed that decisions to expend effort are related to amplification of benefit-versus-cost information attended early in the decision process, whereas the effect of benefits is strengthened with higher synthesis capacity and by methylphenidate. These findings demonstrate that methylphenidate boosts the perceived benefits versus costs of cognitive effort by modulating striatal dopamine signaling.

Molecular identification of the TCA alloantigen as the transferrin receptor on T-cells of a leukemic patient with serum from a monozygotic twin brother.

The transferrin receptor is encoded by a diallelic locus which had been described as the T-cell antigenic system TCA. Using a human lymphoblastoid T-cell line (HSB) which reportedly carries a transferrin receptor and which we showed to be TCA-2 positive by serology, it appeared that only a TCA-2 but not a TCA-1 specific alloantiserum had the capacity to precipitate a protein with a molecular weight of 94,000, which comigrated exactly with the Mr 94,000 protein precipitated by the rabbit anti-HSB and rabbit anti-SB antisera, as well as the transferrin receptor which was precipitated by a transferrin-antitransferrin complex. The positive sera and the latter complex were shown to cross-react in a binding assay. Conversely, a monospecific TCA-1 alloantiserum was shown to react with the Mr 94,000 protein of TCA-1-positive leukocyte suspensions. The allelomorphism of the transferrin receptor may be relevant for the eventual regulatory mechanism controlling cell proliferation, which would be essential at least for those cells that are supposed to play an immunological role like the TCA-positive cells which are described as T-cells probably involved in the process of immunosuppression. In addition, we found increasing amounts of autoantibodies with TCA-1 specificity in serum from a healthy individual (referred to as "donor" in this paper), whose brother at the same time suffered a chronic myeloid leukemia, probably associated with a retrovirus, and whose blood in contrast was shown to contain cytotoxic anti-TCB, from a diallelic locus expressed on theophylline-insensitive T-cells, and anti-B-cell activity.

Synthesis of a viral protein with molecular weight of 30,000 (p30) by leukemic cells and antibodies cross-reacting with Simian sarcoma virus p30 in serum of a chronic myeloid leukemia patient.

We studied a patient with a Philadelphia chromosome-positive chronic myeloid leukemia, who died in relapse after multiple transfusions and grafting with bone marrow from his monozygotic twin brother (referred to as "donor" in this paper). We present data indicating that this patient may have had a retro-virus infection that this virus is related to the group of exogenous primate type C retroviruses. Antibodies to simian sarcoma virus (SSV) M.W. 30,000 protein (p30) but not endogenous feline virus RD-114 could be found in patient but not donor serum. Patient but not donor cells were able to actively synthesize a p30 protein that could be precipitated with patient serum and rabbit anti-SSV p30 but not with donor serum or rabbit anti-RD 114 p30. Patient p30 resembles SSV p30 but not RD-114 p30 in peptide mapping by limited proteolysis and subsequent slab gel electrophoresis. Patient but not donor cells were able to actively synthesize a M.W. 78,000 protein that could be precipitated with goat anti-SSV. An enzyme with properties of reverse transcriptase was increased 30-fold ion patient cells when compared with donor and other control cells. Related to the presence of widespread infectious agents may be the finding that, in the course of the patient's disease, donor serum showed increasing amounts of possibly immunoregulatory (Cancer Research, submitted for publication) antibodies, reactive with autologous and, more effectively, with patient-derived cell membrane M. W. 80,000 protein (a possible idiotypic receptor structure) and M.W. 94,000 protein (a T-cell alloantigen).