Torsten Hägerstrand's work was influential to the emergence of human geography as a theoretically sophisticated social science. Focusing on the materiality of everyday life, and the complex ...ecological webs through which human society is made, his writings offered an original set of tools to think about the how and where of communal life. Nonetheless, in much of the North American and British academy, Hägerstrand's work has been relegated to a disciplinary footnote; a writer whose work has been overtaken by more recent developments in social theory. This article re-evaluates the contemporary relevance of Hägerstrand's thought. Drawing on examples, it explores how the social time-space diagramming developed by Hägerstrand might be productively reinterpreted and reconfigured. Rather than thinking of Hägerstrand's work as being made redundant by subsequent theoretical advances, this paper demonstrates how his work still offers social scientists useful tools to describe the worlds they study.
Mycofactocin (MFT) is a putative ribosomally synthesized and post-translationally modified (RiPP) redox cofactor. The biosynthesis of MFT is encoded by the gene cluster mftABCDEF. While processing of ...the precursor peptide by MftB, MftC, and MftE has been shown to result in the formation of the small molecule 3-amino-5-(p-hydroxyphenyl)methyl-4,4-dimethyl-2-pyrrolidinone (AHDP), no activity has been shown for the putative dehydrogenase MftD and the putative glycosyltransferase MftF. In addition, evidence demonstrating that MFT is a redox cofactor has only been limited to the requirement of mft genes for ethanol assimilation in Mycobacterium smegmatis mc2155. Here, we demonstrate that MftD catalyzes the oxidative deamination of AHDP, forming an α-keto moiety on the resulting molecule, which we call pre-mycofactocin (PMFT). We characterize PMFT by 1D and 2D NMR spectroscopy techniques and by high-resolution mass spectrometry data to solve its structure. We further characterized PMFT by cyclic voltammetry and found its midpoint potential to be ∼255 mV. Lastly, we demonstrate that PMFT is a biologically active redox cofactor that oxidizes NADH bound by M. smegmatis carveol dehydrogenase (MsCDH) and can be used by MsCDH in the oxidation of carveol. These data demonstrate for the first time that PMFT functions as a biologically active redox mediator and provides the most direct evidence to date that MFT is a RiPP-derived redox cofactor.
Three-dimensional (3D) organization of the human genome plays an essential role in all DNA-templated processes, including gene transcription, gene regulation, and DNA replication. Computational ...modeling can be an effective way of building high-resolution genome structures and improving our understanding of these molecular processes. However, it faces significant challenges as the human genome consists of over 6 × 10
base pairs, a system size that exceeds the capacity of traditional modeling approaches. In this perspective, we review the progress that has been made in modeling the human genome. Coarse-grained models parameterized to reproduce experimental data via the maximum entropy optimization algorithm serve as effective means to study genome organization at various length scales. They have provided insight into the principles of whole-genome organization and enabled de novo predictions of chromosome structures from epigenetic modifications. Applications of these models at a near-atomistic resolution further revealed physicochemical interactions that drive the phase separation of disordered proteins and dictate chromatin stability in situ. We conclude with an outlook on the opportunities and challenges in studying chromosome dynamics.
The brains of humans and other mammals are highly vulnerable to interruptions in blood flow and decreases in oxygen levels. Here we describe the restoration and maintenance of microcirculation and ...molecular and cellular functions of the intact pig brain under ex vivo normothermic conditions up to four hours post-mortem. We have developed an extracorporeal pulsatile-perfusion system and a haemoglobin-based, acellular, non-coagulative, echogenic, and cytoprotective perfusate that promotes recovery from anoxia, reduces reperfusion injury, prevents oedema, and metabolically supports the energy requirements of the brain. With this system, we observed preservation of cytoarchitecture; attenuation of cell death; and restoration of vascular dilatory and glial inflammatory responses, spontaneous synaptic activity, and active cerebral metabolism in the absence of global electrocorticographic activity. These findings demonstrate that under appropriate conditions the isolated, intact large mammalian brain possesses an underappreciated capacity for restoration of microcirculation and molecular and cellular activity after a prolonged post-mortem interval.
The health consequences of marital dissolution are well known, but little work has examined the impact of health on the risk of marital dissolution. We use a sample of 2,701 marriages from the Health ...and Retirement Study to examine the role of serious physical illness onset in subsequent marital dissolution via either divorce or widowhood. We use a series of discrete time event history models with competing risks to estimate the impact of husband’s and wife’s physical illness onset on risk of divorce and widowhood. We find that only measures of wife’s illness onset are associated with elevated risk of divorce, while measures of either spouse’s illness onset is associated with elevated risk of widowhood. Further, in the case of heart problems, we find that this gender difference is statistically significant. These findings suggest health as a determinant of marital dissolution in later life via both biological and gendered social pathways.
We investigated, experimentally, the contention that the folk
view
, or naïve
theory
, of time, amongst the population we investigated (i.e. U.S. residents) is dynamical. We found that amongst that ...population, (i) ~ 70% have an extant theory of time (the theory they deploy after some reflection, whether it be naïve or sophisticated) that is more similar to a dynamical than a non-dynamical theory, and (ii) ~ 70% of those who deploy a naïve theory of time (the theory they deploy on the basis of naïve interactions with the world and not on the basis of scientific investigation or knowledge) deploy a naïve theory that is more similar to a dynamical than a non-dynamical theory. Interestingly, while we found stable results across our two experiments regarding the percentage of participants that have a dynamical or non-dynamical extant theory of time, we did not find such stability regarding which
particular
dynamical or non-dynamical theory of time they take to be most similar to our world. This suggests that there might be two extant theories in the population—a broadly dynamical one and a broadly non-dynamical one—but that those theories are sufficiently incomplete that participants do not
stably
choose the
same
dynamical (or non-dynamical) theory as being most similar to our world. This suggests that while appeals to the ordinary view of time may do some work in the context of adjudicating disputes between dynamists and non-dynamists, they likely cannot do any such work adjudicating disputes between particular brands of dynamism (or non-dynamism).
This research tests whether childhood conditions are associated with trajectories of chronic conditions among older adults.
Using data from the Health and Retirement Study (1992-2008), a series of ...hierarchical linear models are used to estimate number of chronic conditions at survey midpoint and the rate of increase in chronic conditions across 18 years of data.
Results suggest that lower childhood socioeconomic status (SES) and poor childhood health are associated with increased number of chronic conditions; however, childhood SES is no longer associated with chronic conditions after adjustment for adult SES and adult health. Poor childhood health continues to be associated with total number of chronic conditions after adjustment for adult SES and health. Rate of change in chronic conditions was not associated with childhood conditions. Results from a multinomial logistic regression model further indicated that the association between childhood conditions and adult multimorbidity increased at higher levels of multimorbidity.
This research adds to the evidence that early life conditions have a lasting influence on adult health, and that their influence may be independent of adult health and SES.
Abstract
We present the results of a spectroscopic monitoring program of the Pleiades region aimed at completing the census of spectroscopic binaries in the cluster, extending it to longer periods ...than previously reachable. We gathered 6104 spectra of 377 stars between 1981 and 2021, and merged our radial velocities with 1151 measurements from an independent survey by others started three years earlier. With the combined data spanning more than 43 yr, we have determined orbits for some 30 new binary and multiple systems, more than doubling the number previously known in the Pleiades. The longest period is 36.5 yr. A dozen additional objects display long-term trends in their velocities, implying even longer periods. We examine the collection of orbital elements for cluster members, and find that the shape of the incompleteness-corrected distribution of periods (up to 10
4
days) is similar to that of solar-type binaries in the field, while that of the eccentricities is different. The mass-ratio distribution is consistent with being flat. The binary frequency in the Pleiades for periods up to 10
4
days is 25% ± 3% after corrections for undetected binaries, which is nearly double that of the field up to the same period. The total binary frequency including known astrometric binaries is at least 57%. We estimate the internal radial velocity dispersion in the cluster to be 0.48 ± 0.04 km s
−1
. We revisit the determination of the tidal circularization period, and confirm its value to be 7.2 ± 1.0 days, with an improved precision compared to an earlier estimate.