Search

Increasing evidence documents turnover of the resting-state blood-oxygen-level dependent signal (TBOLD) as a key measure of local cortical brain status. Here we evaluated contemporaneous and lagged associations between TBOLD and cognitive function in 711 participants in the Human Connectome Project on Aging (HCP-A; 316 males and 395 females, age range 36-90 years). We found that TBOLD was negatively associated with Montreal Cognitive Assessment (MoCA) Total scores and with performance on 2 subscales, Delayed Recall and Visuospatial/Executive Function, controlling for sex, age, and handedness. This negative association was largely documented across brain areas and was significantly stronger in the left hemisphere compared to the right. In addition, analyses evaluating forward lagged crosscorrelations between TBOLD and cognitive performance demonstrated that TBOLD predicted decrements in future performance on MoCA Total score, Delayed Recall, and Visuospatial/Executive Function subscales, controlling for sex and handedness. Taken together, we found that increased TBOLD is associated with decreased cognitive performance contemporaneously and in the future. On the hypothesis that increased TBOLD is the outcome of neuroinflammatory processes, these findings provide a mechanism linking neuroinflammation with decreased cognitive performance. [ABSTRACT FROM AUTHOR]

The blood oxygenation level-dependent (BOLD) activation reflects hemodynamic events mediated by neurovascular coupling. During task performance, the BOLD hemodynamic response in a relevant area is mainly driven by the high levels of synaptic activity (reflected in local field potentials, LFPs) but, in contrast, during a task-free, resting state, the contribution to BOLD of such neural events is small, as expected by the comparatively (to the task state) low level of neural events. Concomitant recording of BOLD and LFP at rest in animal experiments has estimated the neural contribution to BOLD to ∼10%. Such experiments have not been performed in humans. As an approximation, we recorded (in the same subject, n = 57 healthy participants) at a task-free, resting state the BOLD signal and, in a different session, the magnetoencephalographic (MEG) signal, which reflects purely neural (synaptic) events. We then calculated the turnover of these signals by computing the successive moment-to-moment difference in the BOLD and MEG time series and retaining the median of the absolute value of the differenced series (BOLD and TMEG, respectively). The correlation between normalized turnovers of BOLD (TBOLD) and turnovers of MEG (TMEG) was r = 0.336 (r2 = 0.113; P = 0.011). These results estimate that 11.3% of the variance in TBOLD can be explained by the variance in TMEG. This estimate is close to the aforementioned estimate obtained by direct recordings in animal experiments. NEW & NOTEWORTHY: Here, we report on a weak positive association between turnovers of blood oxygenation level-dependent (TBOLD) and magnetoencephalographic (TMEG) signals in 57 healthy human subjects in a resting, task-free state. More specifically, we found that the purely neural TMEG accounted for 11.1% of the TBOLD, a percentage remarkably close to that found between resting-state local field potentials (LFPs) and BOLD recorded concurrently in animal experiments. [ABSTRACT FROM AUTHOR]

Objective: Host immunogenetics (Human Leukocyte Antigen, HLA) play a critical role in the human immune response to melanoma, influencing both melanoma prevalence and immunotherapy outcomes. Beneficial outcomes hinge on the successful binding of epitopes of melanoma antigens to HLA Class I molecules for an effective engagement of cytotoxic CD8+ lymphocytes and subsequent elimination of the cancerous cell. This study evaluated the binding affinity and immunogenicity of HLA Class I to melanoma tumor antigens to identify alleles best suited to facilitate elimination of melanoma antigens. Methods: In this study, we used freely available software tools to determine in silico the binding affinity and immunogenicity of 2462 reported HLA Class I alleles to all linear nonamer epitopes of 11 known antigens expressed in melanoma tumors (TRP2, S100, Tyrosinase, TRP1, PMEL(17), MAGE1, MAGE4, CTA, BAGE, GAGE/SSX2, Melan). Results: We identified the following 9 HLA Class I alleles with very high immunogenicity and binding affinity against all 11 melanoma antigens: A*02:14, B*07:10, B*35:10, B*40:10, B*40:12, B*44:10, C*07:11, and C*07:13, and C*07:14. Conclusion: These 9 HLA alleles possess the potential to aid in the elimination of melanoma both by themselves and by enhancing the beneficial effect of immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Identification of early influences on cognitive decline is of paramount importance in order to stem the impacts of decrements in cognitive functioning and to potentially intervene. Thus, here we focused on 132 healthy adult women (age range 26-98 years) to (a) determine whether factors circulating in serum may exert neurotoxic effects in vitro, (b) evaluate associations between serum neurotoxicity and cognitive performance, and (c) assess the influence of human herpes virus (HHV) seroprevalence and other factors on apoptosis and cognitive performance. The results documented that the addition of serum from healthy adult women to neural cell cultures resulted in apoptosis, indicating the presence of circulating neurotoxic factors in the serum. Furthermore, apoptosis increased with age, and was associated with decreased cognitive performance. Stepwise regression evaluating the influence of 6 HHVs on apoptosis and cognitive function revealed that only HHV5 (cytomegalovirus; CMV) seropositivity was significantly associated with apoptosis and cognitive decline, controlling for age. These findings document neurotoxic effects of serum from healthy women across the adult lifespan and suggest a unique detrimental influence associated with CMV seropositivity. [ABSTRACT FROM AUTHOR]

Previous research has documented elevated risk of brain cancer in patients with multiple sclerosis (MS). Separately, human leukocyte antigen (HLA) has been implicated in protection or susceptibility for both conditions. The aim of the current study was to assess a possible role of shared immunogenetic influence on risk of MS and brain cancer. We first identified an immunogenetic profile for each condition based on the covariance between the population frequency of 127 high-resolution HLA alleles and the population prevalence of each condition in 14 Continental Western European countries and then evaluated the correspondence between MS and brain cancer immunogenetic profiles. Also, since each individual carries 12 HLA alleles (2 × 6 genes), we estimated HLA protection and susceptibility for MS and brain cancer at the individual level. We found that the immunogenetic profiles of MS and brain cancer were highly correlated overall (P <.001) and across all 6 HLA genes with the strongest association observed for DRB1, followed by DQB1 and HLA-A. These findings of immunogenetic overlap between MS and brain cancer are discussed in light of the role of HLA in the immune system response to viruses and other foreign antigens. [ABSTRACT FROM AUTHOR]