Astrocytes undergo an inflammatory transition after infections, acute injuries and chronic neurodegenerative diseases. How this transition is affected by time and sex, its heterogeneity at the ...single-cell level and how sub-states are spatially distributed in the brain remains unclear. In this study, we investigated transcriptome changes of mouse cortical astrocytes after an acute inflammatory stimulus using the bacterial cell wall endotoxin lipopolysaccharide. We identified fast transcriptomic changes in astrocytes occurring within hours that drastically change over time. By sequencing ~80,000 astrocytes at single-cell resolution, we show that inflammation causes a widespread response with subtypes of astrocytes undergoing distinct inflammatory transitions with defined transcriptomic profiles. We also attribute key sub-states of inflammation-induced reactive astrocytes to specific brain regions using spatial transcriptomics and in situ hybridization. Together, our datasets provide a powerful resource for profiling astrocyte heterogeneity and will be useful for understanding the biological importance of regionally constrained reactive astrocyte sub-states.
Human impacts on Earth are now so great that they have led to the concept of a new geological epoch defined by this global human influence: the Anthropocene. While not universally accepted, the term ...is increasingly popular and widely used. However, even among proponents, there is considerable debate regarding when the epoch may have started, from coeval with the Holocene, through the Industrial Revolution, to the mid-20th century when unprecedented human activities resulted in exponential increases in population, resource consumption, and pollutant emission. Recently, this latter period, known as the Great Acceleration, appears to be becoming the more widely accepted start date. To define any start point, a global stratigraphic marker or Global Boundary Stratotype Section and Point (GSSP) is typically required. Here, spheroidal carbonaceous fly ash particles (SCPs), byproducts of industrial fossil-fuel combustion, are proposed as a primary marker for a GSSP at the time of the Great Acceleration. Data from over 75 lake sediment records show a global, synchronous, and dramatic increase in particle accumulation starting in c. 1950 driven by the increased demand for electricity and the introduction of fuel-oil combustion, in addition to coal, as a means to produce it. SCPs are morphologically distinct and solely anthropogenic in origin, providing an unambiguous marker. This is a clear signal of great stratigraphic utility representing a primary driving force for global anthropogenic change.
Knight and Cavusgil's award-winning article has played an important role in the development of the growing body of research on companies that internationalize early and rapidly. These "born global" ...firms represent important contributors to many economies, often as key players in ecosystems that support large multinational enterprises. Despite their growing importance, our understanding of how and why these firms develop and implement their internationalization strategies, and what makes them successful, remains incomplete. Addressing such questions has contributed substantially to the development of the research domain of international entrepreneurship (IE), which focuses on entrepreneurial aspects of doing business across borders, in the context of both small and large firms. While IE is much broader than born globals, these firms are central to the IE domain and the impact of the Knight and Cavusgil paper has helped to develop a stronger awareness of the important linkages and intersections between IE and the wider international business research community. We reflect on the important contribution of this paper, and suggest some directions for the future development of research into firms that choose to operate internationally practically from the start of their operations.
Quantum memories for light will be essential elements in future long-range quantum communication networks. These memories operate by reversibly mapping the quantum state of light onto the quantum ...transitions of a material system. For networks, the quantum coherence times of these transitions must be long compared to the network transmission times, approximately 100 ms for a global communication network. Due to a lack of a suitable storage material, a quantum memory that operates in the 1,550 nm optical fibre communication band with a storage time greater than 1 μs has not been demonstrated. Here we describe the spin dynamics of 167 Er3+ : Y2 SiO5 in a high magnetic field and demonstrate that this material has the characteristics for a practical quantum memory in the 1,550 nm communication band. We observe a hyperfine coherence time of 1.3 s. We also demonstrate efficient spin pumping of the entire ensemble into a single hyperfine state, a requirement for broadband spin-wave storage. With an absorption of 70 dB cm-1 at 1,538 nm and Λ transitions enabling spin-wave storage, this material is the first candidate identified for an efficient, broadband quantum memory at telecommunication wavelengths.
Free Time Rose, Julie L
2016, 2016., 20161101, 2016-11-08
eBook
Recent debates about inequality have focused almost exclusively on the distribution of wealth and disparities in income, but little notice has been paid to the distribution of free time. Free time is ...commonly assumed to be a matter of personal preference, a good that one chooses to have more or less of. Even if there is unequal access to free time, the cause and solution are presumed to lie with the resources of income and wealth. InFree Time, Julie Rose argues that these views are fundamentally mistaken. First, Rose contends that free time is a resource, like money, that one needs in order to pursue chosen ends. Further, realizing a just distribution of income and wealth is not sufficient to ensure a fair distribution of free time. Because of this, anyone concerned with distributive justice must attend to the distribution of free time.
On the basis of widely held liberal principles, Rose explains why citizens are entitled to free time-time not committed to meeting life's necessities and instead available for chosen pursuits. The novel argument that the just society must guarantee all citizens their fair share of free time provides principled grounds to address critical policy choices, including work hours regulations, Sunday closing laws, public support for caregiving, and the pursuit of economic growth.
Delving into an original topic that touches everyone,Free Timedemonstrates why all citizens have, in the words of early labor reformers, a right to "hours for what we will."
The K = 2 conundrum Janes, Jasmine K.; Miller, Joshua M.; Dupuis, Julian R. ...
Molecular ecology,
July 2017, Letnik:
26, Številka:
14
Journal Article
Recenzirano
Odprti dostop
Assessments of population genetic structure have become an increasing focus as they can provide valuable insight into patterns of migration and gene flow. structure, the most highly cited of several ...clustering‐based methods, was developed to provide robust estimates without the need for populations to be determined a priori. structure introduces the problem of selecting the optimal number of clusters, and as a result, the ΔK method was proposed to assist in the identification of the “true” number of clusters. In our review of 1,264 studies using structure to explore population subdivision, studies that used ΔK were more likely to identify K = 2 (54%, 443/822) than studies that did not use ΔK (21%, 82/386). A troubling finding was that very few studies performed the hierarchical analysis recommended by the authors of both ΔK and structure to fully explore population subdivision. Furthermore, extensions of earlier simulations indicate that, with a representative number of markers, ΔK frequently identifies K = 2 as the top level of hierarchical structure, even when more subpopulations are present. This review suggests that many studies may have been over‐ or underestimating population genetic structure; both scenarios have serious consequences, particularly with respect to conservation and management. We recommend publication standards for population structure results so that readers can assess the implications of the results given their own understanding of the species biology.
Plant secondary metabolites (PSMs) are ubiquitous in plants and playmany ecological roles. Each compound can vary in presence and/or quantity, and the composition of the mixture of chemicals can ...vary, such that chemodiversity can be partitioned within and among individuals. Plant ontogeny and environmental and genetic variation are recognized as sources of chemical variation, but recent advances in understanding the molecular basis of variation may allow the future deployment of isogenic mutants to test the specific adaptive function of variation in PSMs. An important consequence of high intraspecific variation is the capacity to evolve rapidly. It is becoming increasingly clear that trait variance linked to both macro- and micro-environmental variation can also evolve and mayrespond more strongly to selection than mean trait values. This research, which is in its infancy in plants, highlights what could be a missing piece of the picture of PSM evolution. PSM polymorphisms are probably maintained by multiple selective forces acting across many spatial and temporal scales, but convincing examples that recognize the diversity of plant population structures are rare. We describe how diversity can be inherently beneficial for plants and suggest fruitful avenues for future research to untangle the causes and consequences of intraspecific variation.
Summary
This review focuses on the disclosure decisions faced by employees with concealable stigmatized identities—one of the most challenging decisions these individuals must make on a day‐to‐day ...basis. Indeed, multiple theoretical frameworks have provided a foundation for understanding the antecedents and outcomes associated with the decision to disclose or not to disclose a stigmatized identity. What is less clear, however, is the extent to which these frameworks have been empirically supported. This systematic review serves to unify the extant literature and prompt continued research related to employees with concealable stigmatized identities. Specifically, we draw upon multiple fields of study, including applied psychology, management, social psychology, and occupational health as a means to systematically synthesize the existing empirical research related to disclosure of stigmatized identities at work. In addition to advancing the scholarly knowledge of disclosure, this review also provides practical utility to organizations as they continue to create work environments that foster inclusion of all stigmatized and nonstigmatized employees.
The ATR replication checkpoint ensures that stalled forks remain stable when replisome movement is impeded. Using an improved iPOND protocol combined with SILAC mass spectrometry, we characterized ...human replisome dynamics in response to fork stalling. Our data provide a quantitative picture of the replisome and replication stress response proteomes in 32 experimental conditions. Importantly, rather than stabilize the replisome, the checkpoint prevents two distinct types of fork collapse. Unsupervised hierarchical clustering of protein abundance on nascent DNA is sufficient to identify protein complexes and place newly identified replisome-associated proteins into functional pathways. As an example, we demonstrate that ZNF644 complexes with the G9a/GLP methyltransferase at replication forks and is needed to prevent replication-associated DNA damage. Our data reveal how the replication checkpoint preserves genome integrity, provide insights into the mechanism of action of ATR inhibitors, and will be a useful resource for replication, DNA repair, and chromatin investigators.
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•iPOND-SILAC-MS across experimental perturbations identifies protein complexes•ZNF644 forms a complex with G9a/GLP at replication forks•Replisome stabilization is not a major function of the replication checkpoint•The replication checkpoint prevents two distinct types of fork collapse
Dungrawala et al. use quantitative iPOND-mass spectrometry analysis of proteins associated with nascent DNA during replication stress to understand how the replication checkpoint controls the replisome and replication stress response.
•Rationale for defining exosome protein cargo is presented.•Methods for global exosome protein identification are described.•Quantitative proteomics methods, both global and targeted, are ...discussed.•Specific proteomics protocols are provided.
Characterization of exosomal cargo is of significant interest because this cargo can provide clues to exosome biogenesis, targeting, and cellular effects and may be a source of biomarkers for disease diagnosis, prognosis and response to treatment. With recent improvements in proteomics technologies, both qualitative and quantitative characterization of exosomal proteins is possible. Here we provide a brief review of exosome proteomics studies and provide detailed protocols for global qualitative, global quantitative, and targeted quantitative analysis of exosomal proteins. In addition, we provide an example application of a standard global quantitative analysis followed by validation via a targeted quantitative analysis of urine exosome samples from human patients. Advantages and limitations of each method are discussed as well as future directions for exosome proteomics analysis.
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