Men, Women and Emotional Stress Responses

Psychoneuroendocrinology (November 2014) is publishing a fascinating paper authored by Sarah Lupis, Michelle Lerman and Jutta Wolf titled Anger responses to psychosocial stress predict heart rate and cortisol stress responses in men but not women.

473People can experience a wide range of emotions when under stress, including feelings of anger and fear. In recent years researchers have sought to understand how these emotion stress responses are linked to biological stress responses. In particular, some evidence suggests that anger and fear may be linked to cardiovascular changes in differential ways. It is less clear, however, how emotions during stress may predict increases in levels of the stress hormone cortisol. These deficits in our understanding are partly due to the methodological difficulties in measuring emotion in the context of stress. Much prior research has relied solely on retrospective self-report (after the stress has passed, a questionnaire asks a study participant to reflect on how he felt in the moment of stress). By this time, the participant may have forgotten how he felt, or may already be utilizing coping strategies to process those emotions. In addition, he may not feel comfortable reporting how the stressor made him feel, leading to less-than-honest responses. Unsurprisingly, prior research has not shown consistent links between these self-report measures and biological stress responses. In the current study, we therefore added facial coding of emotion expression to assess emotions occurring during stress. Our aim was to determine how expressions of anger and fear were linked to heart rate and cortisol stress responses.

We recruited 32 healthy Brandeis students and exposed them to a brief psychosocial stressor. A certified coder assessed facial expressions shown during the stressful situation. Heart rate and cortisol levels were measured throughout. After the stressor, the participants also self-reported how they felt during the stressor. A first notable finding showed that what participants self-reported feeling and the expressions they actually showed did not correlate. With regards to self-report, men who reported feeling fear showed blunted cortisol stress responses. Consistent with prior research, self-report was otherwise not associated with heart rate or cortisol stress responses. When looking at facial expressions, a consistent pattern appeared: men who showed more anger during the stressful situation also showed exaggerated heart rate and cortisol stress responses. For women, neither anger nor fear were linked to biological stress responses (see Figure).

Our findings first emphasize the importance of assessing emotion using multiple means. In this case, facial expressions revealed an emotion-stress link for males that would not be apparent using self-report alone. Facial coding may thus be a useful addition to current stress paradigms. Further, if men who react with anger in stressful situations do respond with exaggerated stress responses, it could have important down-stream health effects. Exaggerated, prolonged, or dysfunctional stress responses could, over time, lead to changes in basal stress systems. This kind of ‘allostatic load’ is associated with negative health outcomes including diabetes and cardiovascular disease. Anger and fear do not seem to drive these responses in females, and further study is needed to determine if similar relationships exist for a different set of emotions, perhaps self-conscious emotions like shame. By better understanding these relationships, more healthful ways of coping with stress can be developed, which is particularly important given that for many, stress has become an unavoidable part of daily life.

 

Chromosome Tethering in Yeast

On July 14, 2014, PLOS ONE  published a paper from the Haber and Kondev labs. The paper, Effect of chromosome tethering on nuclear organization in yeast, was authored by Baris Avsaroglu, Gabriel Bronk, Susannah Gordon-Messer, Jungoh Ham, Debra A. Bressan, James E. Haber, and Jane Kondev.

by Baris Avsaroglu

Chromosopone.0102474_350mes are folded into the cell nucleus in a non-random fashion. In yeast cells the Rabl model is used to describe the folded state of interphase chromosomes in terms of tethering interactions of the centromeres and the telomeres with the nuclear periphery. By combining theory and experiments, we assess the importance of chromosome tethering in determining the spatial location of genes within the interphase yeast nucleus. Using a well-established polymer model of yeast chromosomes to compute the spatial distributions of several genetic loci, we demonstrate that telomere tethering strongly affects the positioning of genes within the first 10 kb of the telomere. Further increasing the distance of the gene from the telomere reduces the effect of the attachment at the nuclear envelope exponentially fast with a characteristic distance of 20 kb. We test these predictions experimentally using fluorescently labeled genetic loci on chromosome III in wild type and in two mutant yeast strains with altered tethering interactions. For all the cases examined we find good agreement between theory and experiment. This study provides a quantitative test of the polymer model of yeast chromosomes, which can be used to predict long-ranged interactions between genetic loci relevant in transcription regulation and DNA recombination.

The “Fly on the Wall” Blog

fruit_fly_drawingBethany Christmann, a Neuroscience Ph.D. student in Leslie Griffith’s lab at Brandeis University has created a blog titled Fly on the Wall. The blog’s purpose is to introduce fly science to a broader audience of non-fly scientists. Check it out if you want to learn more about fly life, current research and how fruit fly research has already made huge contributions to understanding human biology and will continue to do so in the future.

Learn more about research in the Griffith Lab.

 

Patching Up Broken Chromosomes

Olga Tsaponina and James Haber’s recent paper “Frequent Interchromosomal Template Switches during Gene Conversion in S. cerevisiae” was published online by Molecular Cell on July 24, 2014.

by James Haber

“The process of copying DNA every time our cells divide is exceptionally accurate, but in copying 6,000,000,000 base pairs of the genome mistakes do occur, including both mutations and the formation of chromosome breaks. These breaks must be repaired to maintain the integrity of our chromosomes.  In our recent paper we have demonstrated that the mechanism of patching up a broken chromosome is associated with a surprisingly high level of alterations of the sequence.  Many of these changes result from “slippage” of the DNA polymerases copying the DNA during the repair process; for example in copying a sequence of 4 Gs, the polymerase occasionally jumps over one, to lose a base from the sequence (a frameshift mutation).

graphical_abstract_350In this paper we focused on more dramatic slippage events in which the copying machinery jumped from one chromosome to a related but divergent sequence on another chromosome and then jumped back, creating a chimeric sequence.  These interchromosomal template switches (ICTS) occur at a low rate when the distant sequence is only 71% identical, but if we make that segment 100% identical we could find such jumps 10,000 times more frequently, in about 1 in 300 events.  This result reveals how unstable the copying machinery in DNA repair is compared to normal DNA replication. This was very surprising and provides an explanation for many complex rearrangements associated with cancers.  In carrying out this work we identified the first protein that is needed to permit these frequent jumps: a chromatin remodeling enzyme known as Rdh54 that previously did not have a well-defined role in DNA repair in somatic cells.

Finally, we learned a new role for the proteins that survey the genome for mismatched bases that arise during replication and found that one of these proteins, Msh6, is required to specify which strand of DNA containing a mismatch is the “good one” that should be used as the template to correct the mismatch.

This work was supported by the National Institutes of Health General Medical Institute”.

Art Wingfield Festschrift – “Age, Hearing, and Speech Comprehension”

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On July 22nd, 70 colleagues, friends, and students gathered for a festschrift in honor of Art Wingfield, the Nancy Lurie Marks Professor of Neuroscience. The theme of the day was Age, Hearing, and Speech Comprehension, reflecting Art’s research interests.

Brandeis_072214_064In addition to a scientific program composed of talks centered on this topic, the day also featured former students, collaborators, and colleagues sharing stories about Art. These included Stefanie Kuchinsky (2003) who completed a senior honors project in Art’s lab, former postdoc Marianne Fallon, former students Cindy Lahar and Sarah Wayland, and colleagues from the Department of Psychology (Jim Lackner and Paul Dizio).

The day ended with the surprise announcement of the establishment of an annual travel award in Art’s name that will support a graduate student in psychology or neuroscience to travel to a scientific conference, and dinner in town. A great time was had by all!

More information, photos, and stories can be found at www.artwingfieldfest.com.

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Images: Heratch Photography

How regulatory sequences evolve in fruit flies

An IMP-Brandeis collaboration reveals the evolution of regulatory sequences in Drosophilids

By Yuliya Sytnikova and Nelson Lau

Enhancers are cis-regulatory DNA sequences that influence the promoters of genes, but identifying enhancers is not a straightforward process. Previously, the Stark lab developed a method for genome-wide enhancer detection called STARR-seq, (Arnold, Gerlach et al. 2013), that allowed them to identify thousands of enhancer sequences around the Drosophila melanogaster genome. In the most recent issue of Nature Genetics, a collaboration between the Stark lab of the IMP (Institute of Molecular Pathology) in Vienna, Austria, and the Lau lab at Brandeis University examines this hypothesis by studying the conservation of enhancer regulatory regions during Drosophilid fly evolution.

To ask if enhancers from D. melanogaster enhancers are also conserved in other Drosophila species in their sequences and locations, the Stark lab extended the STARR-Seq approach to D.yakuba and D.ananassae, which are separated from D.melanogaster by 11 and 40 million years ago, respectively (Arnold, Gerlach et al. 2014). Interestingly, this study also revealed hundreds of new sequences that gained enhancer function differentially between D.yakuba, D.ananassae, and D.melanogaster.

However, to test if these new sequences meaningfully direct different gene expression changes, the Lau lab conducted a targeted mRNA profiling experiment in purified endogenous follicle cells from D.yakuba and D.ananassae. The Stark lab had initiated the STARR-Seq analysis in an Ovarian Somatic Cell (OSC) line, which originated from the follicle cells of D.melanogaster, therefore the profiling of endogenous follicle cells from D.yakuba and D.ananassae was critical. The Lau lab achieved this using a methodology they developed for profiling Piwi-interacting RNAs from these cells (Matts, Synikova et al. 2013).

Figure 6: Evolution of enhancer activity in OSCs and gene expression in follicle cells in vivo.

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Arnold CD, Gerlach D, Spies D, Matts JA, Sytnikova YA, Pagani M, Lau NC, Stark A. Nat Genet. 2014 Jun 8. doi: 10.1038/ng.3009. [Epub ahead of print] Quantitative genome-wide enhancer activity maps for five Drosophila species show functional enhancer conservation and turnover during cis-regulatory evolution.

Matts JA, Sytnikova Y, Chirn GW, Igloi GL, Lau NC. Methods Mol Biol. 2014;1093:123-36. doi: 10.1007/978-1-62703-694-8_10. Small RNA library construction from minute biological samples.

 

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