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"Wright, Matthew"
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Three-dimensional intact-tissue sequencing of single-cell transcriptional states
RNA sequencing samples the entire transcriptome but lacks anatomical information. In situ hybridization, on the other hand, can only profile a small number of transcripts. In situ sequencing technologies address these shortcomings but face a challenge in dense, complex tissue environments. Wang et al. combined an efficient sequencing approach with hydrogel-tissue chemistry to develop a multidisciplinary technology for three-dimensional (3D) intact-tissue RNA sequencing (see the Perspective by Knöpfel). More than 1000 genes were simultaneously mapped in sections of mouse brain at single-cell resolution to define cell types and circuit states and to reveal cell organization principles. Science , this issue p. eaat5691 ; see also p. 328 Wang et al . describe the development and application of an RNA sequencing technology to define cell types and circuit states in the mouse brain. Retrieving high-content gene-expression information while retaining three-dimensional (3D) positional anatomy at cellular resolution has been difficult, limiting integrative understanding of structure and function in complex biological tissues. We developed and applied a technology for 3D intact-tissue RNA sequencing, termed STARmap (spatially-resolved transcript amplicon readout mapping), which integrates hydrogel-tissue chemistry, targeted signal amplification, and in situ sequencing. The capabilities of STARmap were tested by mapping 160 to 1020 genes simultaneously in sections of mouse brain at single-cell resolution with high efficiency, accuracy, and reproducibility. Moving to thick tissue blocks, we observed a molecularly defined gradient distribution of excitatory-neuron subtypes across cubic millimeter–scale volumes (>30,000 cells) and a short-range 3D self-clustering in many inhibitory-neuron subtypes that could be identified and described with 3D STARmap.
Journal Article
The lost plays of Greek tragedy. Volume 2, Aeschylus, Sophocles and Euripides
The surviving works of Aeschylus, Sophocles and Euripides have been familiar to readers and theatregoers for centuries; but these works are far outnumbered by their lost plays. Between them these authors wrote around two hundred tragedies, the fragmentary remains of which are utterly fascinating. In this, the second volume of a major new survey of the tragic genre, Matthew Wright offers an authoritative critical guide to the lost plays of the three best-known tragedians. The other Greek tragedians and their work are discussed in Volume 1: Neglected Authors. What can we learn about the lost plays of Aeschylus, Sophocles and Euripides from fragments and other types of evidence? How can we develop strategies or methodologies for `reading' lost plays? Why were certain plays preserved and transmitted while others disappeared from view?
BOOK
Diagnosis and management of ventricular tachycardia
Ventricular tachycardia (VT) describes rapid heart rhythms originating from the ventricles. Accurate diagnosis of VT is important to allow prompt referral to specialist services for ongoing management. The diagnosis of VT is usually made based on electrocardiographic data, most commonly 12-lead echocardiography (ECG), as well as supportive cardiac telemetric monitoring. Distinguishing between VT and supraventricular arrhythmias on ECG can be difficult. However, the VT diagnosis frequently needs to be made rapidly in the acute setting. In this review, we discuss the definition of VT, review features of wide-complex tachycardia (WCT) on ECG that might be helpful in diagnosing VT, discuss the different substrates in which VT can occur and offer brief comments on management considerations for patients found to have VT.
Journal Article
\Utter Failure\ or Unity out of Diversity? Debating and Evaluating Policies of Multiculturalism
Across immigrant‐receiving democracies, “multiculturalism” has come under assault by political decision‐makers and commentators. The academic debate, while less fiery, is also heated. We start by outlining the multiple meanings of “multiculturalism”: a term for demographic diversity; a political philosophy of equality or justice; a set of policies to recognize and accommodate ethno‐racial and religious diversity; or a public discourse recognizing and valorizing pluralism. We then review the existing empirical literature and offer some new statistical analyses to assess what we know about the harm or benefits of multicultural policies, focusing on sociopolitical outcomes. We conclude that multicultural policies appear to have some modest positive effects on sociopolitical integration for first‐generation immigrants and likely little direct effect, positive or negative, on those in the second generation. On the question of majority backlash, the limited scholarship is mixed; we speculate that multiculturalism works best in places where both minorities and majority residents see it as part of a common national project. We end by considering the conditions under which this happens and whether there are distinctions between “Anglo‐settler” and other countries.
Journal Article
Gating of social reward by oxytocin in the ventral tegmental area
The reward generated by social interactions is critical for promoting prosocial behaviors. Here we present evidence that oxytocin (OXT) release in the ventral tegmental area (VTA), a key node of the brain’s reward circuitry, is necessary to elicit social reward. During social interactions, activity in paraventricular nucleus (PVN) OXT neurons increased. Direct activation of these neurons in the PVN or their terminals in the VTA enhanced prosocial behaviors. Conversely, inhibition of PVN OXT axon terminals in the VTA decreased social interactions. OXT increased excitatory drive onto reward-specific VTA dopamine (DA) neurons. These results demonstrate that OXT promotes prosocial behavior through direct effects on VTA DA neurons, thus providing mechanistic insight into how social interactions can generate rewarding experiences.
Journal Article
Psychological Well-being Among Older Adults: The Role of Partnership Status
Today's older adults are increasingly unmarried. Some are in cohabiting unions, others are dating, and many remain unpartnered. Unmarried older adults are at risk of poorer well-being than married older adults, but it is unclear whether older cohabitors fare worse than or similar to their married counterparts; nor have well-being differences among cohabitors, daters, and unpartnered persons been considered. Conceptualizing marital status as a continuum of social attachment, data from Waves I and II of the National Social Life, Health, and Aging Project are used to examine how older married, cohabiting, dating, and unpartnered individuals differ across multiple indicators of psychological well-being. Among men, cohabitors appear to fare similarly to the married, and better than daters and the unpartnered. In contrast, there are few differences in psychological well-being by partnership status for women.
Journal Article
Marriage, Cohabitation, and Divorce in Later Life
Older adults are at the forefront of family change as a declining share experiences lifelong marriage and rates of cohabitation and divorce in later life continue to rise. The goal of this article is to review recent scholarship on marriage, cohabitation, and divorce among older adults and identify directions for future research. The varied family experiences characterizing the later life course demonstrate the importance of moving beyond marital status to capture additional dimensions of the marital biography, including transitions, timing, duration, and sequencing. Cohabitation operates as an alternative to marriage for older adults and is increasingly replacing remarriage following divorce or widowhood. The gray divorce rate has doubled in recent decades as older adults abandon marriage in favor of unmarried partnerships or singlehood. The retreat from marriage among older adults raises important questions about the ramifications of family change for health and well-being as well as access to caregivers given that spouses historically have been the primary source of care.
Journal Article
Repartnering Following Gray Divorce: The Roles of Resources and Constraints for Women and Men
The doubling of the gray divorce rate (i.e., divorce at age 50 or older) over the past few decades portends growth in later-life repartnering, yet little is known about the mechanisms undergirding decisions to repartner after gray divorce. Using data from the 1998-2014 Health and Retirement Study, we examined women's and men's likelihoods of forming a remarriage or cohabiting union following gray divorce by estimating competing risk multinomial logistic regression models using discrete-time event history data. About 22 % of women and 37 % of men repartnered within 10 years after gray divorce. Repartnering more often occurred through cohabitation than remarriage, particularly for men. Resources such as economic factors, health, and social ties were linked to repartnering, but constraints captured by the contours of the marital biography were also salient, underscoring the distinctive features of union formation in later life.
Journal Article