Explore the vast range of titles available.

Many biological processes are executed and regulated through the molecular interactions of proteins and nucleic acids. Proximity labeling (PL) is a technology for tagging the endogenous interaction partners of specific protein ‘baits’, via genetic fusion to promiscuous enzymes that catalyze the generation of diffusible reactive species in living cells. Tagged molecules that interact with baits can then be enriched and identified by mass spectrometry or nucleic acid sequencing. Here we review the development of PL technologies and highlight studies that have applied PL to the discovery and analysis of molecular interactions. In particular, we focus on the use of PL for mapping protein–protein, protein–RNA and protein–DNA interactions in living cells and organisms.This Review describes proximity labeling methods that make use of peroxidases (APEX) or biotin ligases (TurboID, BioID), and their applications to studying protein–protein and protein–nucleic acid interactions in living systems.

Neural processing occurs across a range of temporal scales. To facilitate this, the brain uses fast-changing representations reflecting momentary sensory input alongside more temporally extended representations, which integrate across both short and long temporal windows. The temporal flexibility of these representations allows animals to behave adaptively. Short temporal windows facilitate adaptive responding in dynamic environments, while longer temporal windows promote the gradual integration of information across time. In the cognitive and motor domains, the brain sets overarching goals to be achieved within a long temporal window, which must be broken down into sequences of actions and precise movement control processed across much shorter temporal windows. Previous human neuroimaging studies and large-scale artificial network models have ascribed different processing timescales to different cortical regions, linking this to each region’s position in an anatomical hierarchy determined by patterns of inter-regional connectivity. However, even within cortical regions, there is variability in responses when studied with single-neuron electrophysiology. Here, we review a series of recent electrophysiology experiments that demonstrate the heterogeneity of temporal receptive fields at the level of single neurons within a cortical region. This heterogeneity appears functionally relevant for the computations that neurons perform during decision-making and working memory. We consider anatomical and biophysical mechanisms that may give rise to a heterogeneity of timescales, including recurrent connectivity, cortical layer distribution, and neurotransmitter receptor expression. Finally, we reflect on the computational relevance of each brain region possessing a heterogeneity of neuronal timescales. We argue that this architecture is of particular importance for sensory, motor, and cognitive computations.

Competing accounts propose that working memory (WM) is subserved either by persistent activity in single neurons or by dynamic (time-varying) activity across a neural population. Here, we compare these hypotheses across four regions of prefrontal cortex (PFC) in an oculomotor-delayed-response task, where an intervening cue indicated the reward available for a correct saccade. WM representations were strongest in ventrolateral PFC neurons with higher intrinsic temporal stability (time-constant). At the population-level, although a stable mnemonic state was reached during the delay, this tuning geometry was reversed relative to cue-period selectivity, and was disrupted by the reward cue. Single-neuron analysis revealed many neurons switched to coding reward, rather than maintaining task-relevant spatial selectivity until saccade. These results imply WM is fulfilled by dynamic, population-level activity within high time-constant neurons. Rather than persistent activity supporting stable mnemonic representations that bridge subsequent salient stimuli, PFC neurons may stabilise a dynamic population-level process supporting WM. Working memory (WM) is represented in persistent activity of single neurons as well as a dynamic population code. Here, the authors find that neurons flexibly switch their coding according to current attention while those with stable resting activity maintain WM representations through dynamic activity patterns.

Scholars have long looked to family composition to understand child well-being. The study of family instability, or the experience of repeated changes in parents' union status during childhood, represents a recent advance in this field that takes into account the dynamic nature of contemporary family organization and considers its implications for children's adjustment and development. We review some of the structural and cultural factors that have contributed to rising levels of family instability and highlight the emergence of national data to measure it. We then review the perspective that guides much of the scholarship on family instability and critically assess the contributions of this work to the understanding of child well-being. We close by suggesting new directions for research, with a call for work that broadens the conceptualization and measurement of contemporary children's family systems and home environments as well as the mechanisms that explain why-or whether-instability matters.

Correlates of value are routinely observed in the prefrontal cortex (PFC) during reward-guided decision making. In previous work (Hunt et al., 2015), we argued that PFC correlates of chosen value are a consequence of varying rates of a dynamical evidence accumulation process. Yet within PFC, there is substantial variability in chosen value correlates across individual neurons. Here we show that this variability is explained by neurons having different temporal receptive fields of integration, indexed by examining neuronal spike rate autocorrelation structure whilst at rest. We find that neurons with protracted resting temporal receptive fields exhibit stronger chosen value correlates during choice. Within orbitofrontal cortex, these neurons also sustain coding of chosen value from choice through the delivery of reward, providing a potential neural mechanism for maintaining predictions and updating stored values during learning. These findings reveal that within PFC, variability in temporal specialisation across neurons predicts involvement in specific decision-making computations.

This study investigated the association between family instability and children's problem behavior during the transition to first grade. In a sample (n = 1,015) drawn from the NICHD Study of Early Child Care and Youth Development, we found that a quarter of sample members experienced at least one family transition between birth and age 6. Instability was also related to family structure at birth: those born into cohabiting parent families experienced the most instability, followed by those born into single mother families and finally, those in two-biological married parent families. Children who experienced instability had higher teacher and observer reports of problem behaviors than those from stable family structures. Finally, differences in problem behavior associated with family instability varied by family structure at birth and the emotional, social and material resources in the family.

Mitochondria are energy-producing organelles that conduct other key cellular tasks. Thus, mitochondrial damage may impair various aspects of tissue functioning. Mitochondria generate oxygen- and nitrogen-derived oxidants, being themselves major oxidation targets. Dysfunctional mitochondria seem to contribute to the pathophysiology of hypertension, cardiac failure, the metabolic syndrome, obesity, diabetes mellitus, renal disease, atherosclerosis, and aging. Mitochondrial proteins and metabolic intermediates participate in various cellular processes, apart from their well-known roles in energy metabolism. This emphasizes the participation of dysfunctional mitochondria in disease, notwithstanding that most evidences supporting this concept come from animal and cultured-cell studies. Mitochondrial oxidant production is altered by several factors related to vascular pathophysiology. Among these, angiotensin-II stimulates mitochondrial oxidant release leading to energy metabolism depression. By lowering mitochondrial oxidant production, angiotensin-II inhibition enhances energy production and protects mitochondrial structure. This seems to be one of the mechanisms underlying the benefits of angiotensin-II inhibition in hypertension, diabetes, and aging rodent models. If some of these findings can be reproduced in humans, they would provide a new perspective on the implications that RAS-blockade can offer as a therapeutic strategy. This review intends to present available information pointing to mitochondria as targets for therapeutic Ang-II blockade in human renal and CV disease.

The social and human capital that educational attainment provides women enables them to better navigate their children's passages through school. In this study, we examine a key mechanism in this intergenerational process: mothers' selection of early child care. Analyses of the NICHD Study of Early Child Care and Youth Development revealed that maternal education was positively associated with configurations of child-care characteristics (i.e., type, quality, quantity) most closely linked to children's school readiness. This association was not solely a function of mother's income or employment status, persisted despite controls for many observable confounds (e.g., maternal cognitive and psychological skills, paternal characteristics), and, according to post-hoc indices, was fairly robust in terms of unobservable confounds.

This study examined whether the transition into adolescence, proxied by pubertal timing, shaped the transition into adulthood, proxied by union formation behaviors, among contemporary American women. In a sample drawn from Add Health (n = 7,523), early maturing girls reported an accelerated transition to marriage and cohabitation in young adulthood, net of family structure history, academic achievement in high school, and parental education. The link between pubertal timing and cohabitation was strongest among socioeconomically advantaged women; no socio-economic differences were identified for marriage. The tendency for early maturers to have more pronounced romantic orientations during adolescence partially explained their transitions to marriage. In all, the persistence of the pubertal timing effect into young adulthood suggests that early maturers accelerated entrance into the romantic market in adolescence has a cascading, long-term impact on the shape of their lives in young adulthood.