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A proposed unified interphase nucleus chromosome structure: Preliminary preponderance of evidence.

ABSTRACT: Cryoelectron tomography of the cell nucleus using scanning transmission electron microscopy and deconvolution processing technology has highlighted a large-scale, 100- to 300-nm interphase chromosome structure, which is present throughout the nucleus. This study further documents and analyzes these chromosome structures. The paper is divided into four parts: 1) evidence (preliminary) for a unified interphase chromosome structure; 2) a proposed unified interphase chromosome architecture; 3) organization as chromosome territories (e.g., fitting the 46 human chromosomes into a 10-μm-diameter nucleus); and 4) structure unification into a polytene chromosome architecture and lampbrush chromosomes. Finally, the paper concludes with a living light microscopy cell study showing that the G1 nucleus contains very similar structures throughout. The main finding is that this chromosome structure appears to coil the 11-nm nucleosome fiber into a defined hollow structure, analogous to a Slinky helical spring [https://en.wikipedia.org/wiki/Slinky; motif used in Bowerman et al., eLife 10, e65587 (2021)]. This Slinky architecture can be used to build chromosome territories, extended to the polytene chromosome structure, as well as to the structure of lampbrush chromosomes.

SUBMITTER: Sedat J

PROVIDER: S-EPMC9245672 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aims:Dysfunctional brain reward circuitry, particularly in the nucleus accumbens (NAcc), has been proposed as a risk factor for alcohol use disorder (AUD). This risk factor may be evident in binge drinkers (BD), who are at high risk for developing AUD. We examined whole-brain and NAcc reactivity to reward in BD compared to non-binge drinkers (NBD), hypothesizing that groups would differ in their neural reactivity and connectivity. Methods:Healthy BD (N = 27) and NBD (N = 23)-none meeting AUD criteria-completed a reward-guessing game, the 'Doors' task, during functional magnetic resonance imaging. We conducted an exploratory whole-brain search for group differences, but given our a priori hypotheses, we also extracted activation from the NAcc to examine reactivity during reward (Win > Loss) and functional connectivity (FC) to the prefrontal cortex. Results:Compared to NBD, BD exhibited greater activation in both the right and left NAcc during reward relative to loss. Additionally, NBD drinkers exhibited positive FC between the NAcc and dorsal anterior cingulate (dACC) whereas the BD showed negative FC between these regions. Furthermore, less NAcc-dACC FC was related to more past month alcohol use. Conclusions:Our results provide preliminary evidence that BD exhibit greater NAcc activation during reward receipt relative to loss. This is consistent with the broader AUD literature and suggests aberrant neural reactivity may precede disorder onset. In addition, BD exhibited less NAcc-dACC FC, perhaps reflecting deficient regulation of activation to rewards compared to losses. This profile of reward brain circuitry could represent neural correlates of vulnerability for AUD. Short summary:Healthy binge drinkers, at risk for alcohol use disorder, exhibited greater nucleus accumbens activation during reward relative to loss. In addition, binge drinkers exhibited reduced connectivity between the nucleus accumbens and dorsal anterior cingulate, which was associated with more past month alcohol use.

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A proposed unified interphase nucleus chromosome structure: Preliminary preponderance of evidence.

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