Neural evidence for advantaged representation of first items in memory

Visual areas activated during perception can retain specific information held in memory without the presence of physical stimuli via distributed activity patterns. Neuroimaging studies have shown that the delay-period representation of information in visual areas is modulated by factors such as memory load and task demands, raising the possibility of serial position as another potential modulator. Specifically, enhanced representation of first items during the post-encoding delay period may serve as a mechanism underlying the well-established but not well-understood primacy effect – the mnemonic advantage of first items. To test this hypothesis, 13 males and 16 females performed a human fMRI task, wherein each trial consisted of the sequential encoding of two stimuli (a famous face and landscape, order counterbalanced), followed by a distracting task, a delay period, and then a cued recall of one of the items. Participants exhibited the expected behavioral primacy effect, manifested as faster recall of the first items. In order to elucidate the still debated neural underpinnings of this effect, using multivariate decoding, a classifier was trained on data collected during encoding to differentiate stimulus categories (i.e., faces vs. landscapes) and tested on data collected during the post-encoding period. Greater reactivation of first versus second items was observed in the ventral occipito-temporal cortex during the entire post-encoding period but not during encoding. Moreover, trial-level analyses revealed that the degree of first-item neural advantage during the post-encoding delay predicted the behavioral primacy effect. These findings highlight the role of item reinstatement in ventral occipito-temporal cortex in the primacy effect and are discussed in the context of the uniqueness of the very first item and event boundaries, illuminating putative neural mechanisms underlying the effect

Feasibly of CD24/CD11b as a Screening Test for Hematological Malignancies

An estimated 1.24 million blood cancer cases occur annually worldwide, accounting for approximately 6% of all cancer cases. Currently, there are no standardized hematology cancer screening tests that are recommended for the general population. CD24 is a mucin-like cell surface molecule and P-selectin ligand, which plays a significant role in the maturation of B-lymphocytes and was found to be overexpressed in a number of hematological malignancies. Our primary aim was to assess the sensitivity and specificity of the CD24/CD11b-based blood test for the detection of hematological malignancies. Our cohort included 488 subjects with positive hematological cancer diagnosis (n = 122) and healthy subjects (n = 366). CD24/CD11b expression in peripheral blood leukocytes (PBLs) obtained from blood samples of participants was analyzed by flow cytometry. Our results demonstrated that the average levels of CD24/CD11b in healthy patients (21.7 ± 9.0) were statistically significantly lower compared to levels of CD24/CD11b in cancer patients (29.5 ± 18.7, p < 0.001). The highest levels of CD24/CD11b were found in multiple myeloma (39.1 ± 23.6), followed by chronic myeloid leukemia (33.0 ± 13.7) and non-Hodgkin lymphoma (32.3 ± 13.3). The test had an overall sensitivity for hematologic cancers of 78.5% (95% CI, 70.7–86.3%) and specificity of 80.2% (95% CI, 76.1–84.3%). In conclusion, our findings indicate the feasibility of a CD24/CD11b-based blood test as a screening test of hematological malignancies

Human genetics and neuropathology suggest a link between miR-218 and amyotrophic lateral sclerosis pathophysiology

Motor neuron-specific microRNA-218 (miR-218) has recently received attention because of its roles in mouse development. However, miR-218 relevance to human motor neuron disease was not yet explored. Here, we demonstrate by neuropathology that miR-218 is abundant in healthy human motor neurons. However, in amyotrophic lateral sclerosis (ALS) motor neurons, miR-218 is down-regulated and its mRNA targets are reciprocally up-regulated (derepressed). We further identify the potassium channel Kv10.1 as a new miR-218 direct target that controls neuronal activity. In addition, we screened thousands of ALS genomes and identified six rare variants in the human miR-218-2 sequence. miR-218 gene variants fail to regulate neuron activity, suggesting the importance of this small endogenous RNA for neuronal robustness. The underlying mechanisms involve inhibition of miR-218 biogenesis and reduced processing by DICER. Therefore, miR-218 activity in motor neurons may be susceptible to failure in human ALS, suggesting that miR-218 may be a potential therapeutic target in motor neuron disease