Disentangling perceptual awareness from nonconscious processing in rhesus monkeys (Macaca mulatta).

Scholars have long debated whether animals, which display impressive intelligent behaviors, are consciously aware or not. Yet, because many complex human behaviors and high-level functions can be performed without conscious awareness, it was long considered impossible to untangle whether animals are aware or just conditionally or nonconsciously behaving. Here, we developed an empirical approach to address this question. We harnessed a well-established cross-over double dissociation between nonconscious and conscious processing, in which people perform in completely opposite ways when they are aware of stimuli versus when they are not. To date, no one has explored if similar performance dissociations exist in a nonhuman species. In a series of seven experiments, we first established these signatures in humans using both known and newly developed nonverbal double-dissociation tasks and then identified similar signatures in rhesus monkeys (Macaca mulatta). These results provide robust evidence for two distinct modes of processing in nonhuman primates. This empirical approach makes it feasible to disentangle conscious visual awareness from nonconscious processing in nonhuman species; hence, it can be used to strip away ambiguity when exploring the processes governing intelligent behavior across the animal kingdom. Taken together, these results strongly support the existence of both nonconscious processing as well as functional human-like visual awareness in nonhuman animals.

The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA.

Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N(6)-methyladenosine (m(6)A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N(1)-methyladenosine (m(1)A), that occurs on thousands of different gene transcripts in eukaryotic cells, from yeast to mammals, at an estimated average transcript stoichiometry of 20% in humans. Employing newly developed sequencing approaches, we show that m(1)A is enriched around the start codon upstream of the first splice site: it preferentially decorates more structured regions around canonical and alternative translation initiation sites, is dynamic in response to physiological conditions, and correlates positively with protein production. These unique features are highly conserved in mouse and human cells, strongly indicating a functional role for m(1)A in promoting translation of methylated mRNA.

When emotion does and does not impair performance: a Garner theory of the emotional Stroop effect.

It takes people longer to name the ink colour of emotion or threat words than that of neutral words, the emotional Stroop effect (ESE). In three experiments with normal and patient populations, we show that the ESE is a special case of a generic attention model and effect entailed in Garner's speeded classification paradigm. Guided by the Garner model we demonstrate that task-irrelevant dimensions that differ in salience can produce the ESE and mimic it with neutral stimuli. When each word appears in a constant colour, as mandated in the correlation condition of the Garner design, the ESE is eliminated. This important result is consistent with the attention account of the ESE. We conclude that when emotion stimuli appear in a random fashion they interfere with task performance. However, when emotion stimuli are correlated with features of the ongoing task they help task performance not least due to their extreme salience.

Dynamic regulation of N6,2'-O-dimethyladenosine (m6Am) in obesity.

The prevalent m6Am mRNA cap modification was recently identified as a valid target for removal by the human obesity gene FTO along with the previously established m6A mRNA modification. However, the deposition and dynamics of m6Am in regulating obesity are unknown. Here, we investigate the liver m6A/m methylomes in mice fed on a high fat Western-diet and in ob/ob mice. We find that FTO levels are elevated in fat mice, and that genes which lost m6Am marking under obesity are overly downregulated, including the two fatty-acid-binding proteins FABP2, and FABP5. Furthermore, the cellular perturbation of FTO correspondingly affect protein levels of its targets. Notably, generally m6Am- but not m6A-methylated genes, are found to be highly enriched in metabolic processes. Finally, we deplete all m6A background via Mettl3 knockout, and unequivocally uncover the association of m6Am methylation with increased mRNA stability, translation efficiency, and higher protein expression. Together, these results strongly implicate a dynamic role for m6Am in obesity-related translation regulation.

Breaking the Ceiling of Human Maximal Life span.

While average human life expectancy has increased dramatically in the last century, the maximum life span has only modestly increased. These observations prompted the notion that human life span might have reached its maximal natural limit of ~115 years. To evaluate this hypothesis, we conducted a systematic analysis of all-cause human mortality throughout the 20th century. Our analyses revealed that, once cause of death is accounted for, there is a proportional increase in both median age of death and maximum life span. To examine whether pathway targeted aging interventions affected both median and maximum life span, we analyzed hundreds of interventions performed in multiple organisms (yeast, worms, flies, and rodents). Three criteria: median, maximum, and last survivor life spans were all significantly extended, and to a similar extent. Altogether, these findings suggest that targeting the biological/genetic causes of aging can allow breaking the currently observed ceiling of human maximal life span.

The Emotional Stroop Task: Assessing Cognitive Performance under Exposure to Emotional Content.

The emotional Stroop effect (ESE) is the result of longer naming latencies to ink colors of emotion words than to ink colors of neutral words. The difference shows that people are affected by the emotional content conveyed by the carrier words even though they are irrelevant to the color-naming task at hand. The ESE has been widely deployed with patient populations, as well as with non-selected populations, because the emotion words can be selected to match the tested pathology. The ESE is a powerful tool, yet it is vulnerable to various threats to its validity. This report refers to potential sources of confounding and includes a modal experiment that provides the means to control for them. The most prevalent threat to the validity of existing ESE studies is sustained effects and habituation wrought about by repeated exposure to emotion stimuli. Consequently, the order of exposure to emotion and neutral stimuli is of utmost importance. We show that in the standard design, only one specific order produces the ESE.

Speeded naming or naming speed? The automatic effect of object speed on performance.

We test the hypothesis that naming an object depicted in a picture and reading aloud an object's name are affected by the object's speed. We contend that the mental representations of everyday objects and situations include their speed, and that the latter influences behavior in instantaneous and systematic ways. An important corollary is that high-speed objects are named faster than low-speed objects, although object speed is irrelevant to the naming task at hand. The results of a series of 7 studies with pictures and words support these predictions.

FTO: linking m6A demethylation to adipogenesis.

Polymorphism of the FTO gene encoding an N(6)-methyladenosine (m(6)A) RNA demethylase was robustly associated with human obesity; however, the mechanism by which FTO affects metabolism, considering its emerging role in RNA modification, is still poorly understood. A new study published in Cell Research reports novel functions implicating FTO in the regulation of mRNA alternative splicing in the control of adipogenesis.

Stem cells. m6A mRNA methylation facilitates resolution of naïve pluripotency toward differentiation.

Naïve and primed pluripotent states retain distinct molecular properties, yet limited knowledge exists on how their state transitions are regulated. Here, we identify Mettl3, an N(6)-methyladenosine (m(6)A) transferase, as a regulator for terminating murine naïve pluripotency. Mettl3 knockout preimplantation epiblasts and naïve embryonic stem cells are depleted for m(6)A in mRNAs, yet are viable. However, they fail to adequately terminate their naïve state and, subsequently, undergo aberrant and restricted lineage priming at the postimplantation stage, which leads to early embryonic lethality. m(6)A predominantly and directly reduces mRNA stability, including that of key naïve pluripotency-promoting transcripts. This study highlights a critical role for an mRNA epigenetic modification in vivo and identifies regulatory modules that functionally influence naïve and primed pluripotency in an opposing manner.

Pitch memory and exposure effects.

Recent studies indicate that the ability to represent absolute pitch values in long-term memory, long believed to be the possession of a small minority of trained musicians endowed with "absolute pitch," is in fact shared to some extent by a considerable proportion of the population. The current study examined whether this newly discovered ability affects aspects of music and auditory cognition, particularly pitch learning and evaluation. Our starting points are two well-established premises: (1) frequency of occurrence has an influence on the way we process stimuli; (2) in Western music, some pitches and musical keys are much more frequent than others. Based on these premises, we hypothesize that if absolute pitch values are indeed represented in long-term memory, pitch frequency of occurrence in music would significantly affect cognitive processes, in particular pitch learning and evaluation. Two experiments were designed to test this hypothesis in participants with no absolute pitch, most with little or no musical training. Experiment 1 demonstrated a faster response and a learning advantage for frequent pitches over infrequent pitches in an identification task. In Experiment 2, participants evaluated infrequent pitches as more pleasing than frequent pitches when presented in isolation. These results suggest that absolute pitch representation in memory may play a substantial, hitherto unacknowledged role in auditory (and specifically musical) cognition.

Is the emotional Stroop task a special case of mood induction? Evidence from sustained effects of attention under emotion.

Sustained effects of emotion are well known in everyday experience. Surprisingly, such effects are seldom recorded in laboratory studies of the emotional Stroop task, in which participants name the color of emotion and neutral words. Color performance is more sluggish with emotion words than with neutral words, the emotional Stroop effect (ESE). The ESE is not sensitive to the order in which the two groups of words are presented, so the effect of exposure to emotion words does not extend to disrupting performance in a subsequent block with neutral words. We attribute this absence of a sustained effect to habituation engendered by excessive repetition of the experimental stimuli. In a series of four experiments, we showed that sustained effects do occur when habituation is removed, and we also showed that the massive exposure to negative stimuli within the ESE paradigm induces a commensurately negative mood. A novel perspective is offered, in which the ESE is considered a special case of mood induction.