Moshe Shay Ben-Haim

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 N6-methyladenosine (m6A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N1-methyladenosine (m1A), 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 m1A 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 m1A in promoting translation of methylated mRNA.

FTO: linking m6A demethylation to adipogenesis

Polymorphism of the FTO gene encoding an N-methyladenosine (mA) 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.

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.

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 Garners 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.

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.

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.

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 objects name are affected by the objects 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.