Early Xenopus laevis embryogenesis is a robust system for investigating mechanisms of developmental timing. After a series of rapid cell divisions with concomitant reductions in cell size, the first ...major developmental transition is the midblastula transition (MBT), when zygotic transcription begins and cell cycles elongate 1–3. Whereas the maintenance of a constant nuclear-to-cytoplasmic (N/C) volume ratio is a conserved cellular property 4–7, it has long been recognized that the N/C volume ratio changes dramatically during early Xenopus development 8. We investigated how changes in nuclear size and the N/C volume ratio during early development contribute to the regulation of MBT timing. Whereas previous studies suggested a role for the N/C volume ratio in MBT timing 1, 9–13, none directly tested the effects of altering nuclear size. In this study, we first quantify blastomere and nuclear sizes in X. laevis embryos, demonstrating that the N/C volume ratio increases prior to the MBT. We then manipulate nuclear volume in embryos by microinjecting different nuclear scaling factors, including import proteins, lamins, and reticulons. Using this approach, we show that increasing the N/C volume ratio in pre-MBT embryos leads to premature activation of zygotic gene transcription and early onset of longer cell cycles. Conversely, decreasing the N/C volume ratio delays zygotic transcription and leads to additional rapid cell divisions. Whereas the DNA-to-cytoplasmic ratio has been implicated in MBT timing 1, 9–18, our data show that nuclear size also contributes to the regulation of MBT timing, demonstrating the functional significance of nuclear size during development.
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•The N/C volume ratio increases prior to the MBT during Xenopus development•Nuclear size and the N/C volume ratio can be manipulated in Xenopus embryos•Altering the N/C volume ratio changes the timing of zygotic gene transcription•Altering the N/C volume ratio changes the timing of cellular hallmarks of the MBT
Whereas nuclear size is a tightly regulated cellular parameter, little is known about how nuclear size impacts cell function. By manipulating nuclear size in Xenopus embryos, Jevtić and Levy show that the nuclear-to-cytoplasmic volume ratio contributes to proper timing of zygotic transcription and cellular hallmarks of the midblastula transition.
Recombinant adeno-associated virus (rAAV) gene therapy has the potential to transform the lives of patients with certain genetic disorders by increasing or restoring function to affected tissues. ...Following the initial establishment of transgene expression, it is unknown how long the therapeutic effect will last, although animal and emerging human data show that expression can be maintained for more than 10 years. The durability of therapeutic response is key to long-term treatment success, especially since immune responses to rAAV vectors may prevent re-dosing with the same therapy. This review explores the non-immunological and immunological processes that may limit or improve durability and the strategies that can be used to increase the duration of the therapeutic effect.
Durable transgene expression following rAAV gene therapy is key to long-term treatment success; however, it is currently unknown how long the therapeutic effect will last. In this review, Gao and colleagues explore non-immunological and immunological factors that may affect durability, and strategies to potentially optimize the duration of therapeutic effect.
Societies' relative use of private and public services is an abiding and significant issue of scholarly and policy interest. For higher education, however, there has hitherto been no comprehensive ...dataset and, accordingly, no extensive, reliable analysis of the private-public distribution. As this article provides both the dataset and the analysis, it allows us to discover both the size and geographical shape of global private higher education. Having grown greatly for decades, the private sector now holds a third (32.9%) of the world's total higher education enrollment. We find striking patterns of concentration and dispersion. The several largest country systems account for much of the private enrollment but, simultaneously, private sectors now exist in all but a few systems; a stunning 97.6% of the world's present enrollment is in systems with dual-sector provision. Societies no longer rely exclusively on public provision. We discover too that private enrollment concentrates mostly in developing regions, though it is noteworthy in developed regions as well. Asia and Latin America are the twin giants but in all regions, at least 10% of students are in the private sector. (HRK / Abstract übernommen).
Estimating the burden of SARS-CoV-2 in France Salje, Henrik; Tran Kiem, Cécile; Lefrancq, Noémie ...
Science (American Association for the Advancement of Science),
07/2020, Volume:
369, Issue:
6500
Journal Article
Peer reviewed
Open access
France has been heavily affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and went into lockdown on 17 March 2020. Using models applied to hospital and death data, ...we estimate the impact of the lockdown and current population immunity. We find that 2.9% of infected individuals are hospitalized and 0.5% of those infected die (95% credible interval: 0.3 to 0.9%), ranging from 0.001% in those under 20 years of age to 8.3% in those 80 years of age or older. Across all ages, men are more likely to be hospitalized, enter intensive care, and die than women. The lockdown reduced the reproductive number from 2.90 to 0.67 (77% reduction). By 11 May 2020, when interventions are scheduled to be eased, we project that 3.5 million people (range: 2.1 million to 6.0 million), or 5.3% of the population (range: 3.3 to 9.3%), will have been infected. Population immunity appears to be insufficient to avoid a second wave if all control measures are released at the end of the lockdown.
Summary On Sept 29, 2013, the Framingham Heart Study will celebrate 65 years since the examination of the first volunteer in 1948. During this period, the study has provided substantial insight into ...the epidemiology and risk factors of cardiovascular disease. The origins of the study are closely linked to the cardiovascular health of President Franklin D Roosevelt and his premature death from hypertensive heart disease and stroke in 1945. In this Review we describe the events leading to the foundation of the Framingham Heart Study, and provide a brief historical overview of selected contributions from the study.
During early embryogenesis, as cells divide in the developing embryo, the size of intracellular organelles generally decreases to scale with the decrease in overall cell size. Organelle size scaling ...is thought to be important to establish and maintain proper cellular function, and defective scaling may lead to impaired development and disease. However, how the cell regulates organelle size and organization are largely unanswered questions. In this review, we summarize the process of size scaling at both the cell and organelle levels and discuss recently discovered mechanisms that regulate this process during early embryogenesis. In addition, we describe how some recently developed techniques and Xenopus as an animal model can be used to investigate the underlying mechanisms of size regulation and to uncover the significance of proper organelle size scaling and organization.
Orienting of visual attention in aging Erel, Hadas; Levy, Daniel A.
Neuroscience and biobehavioral reviews,
October 2016, 2016-Oct, 2016-10-00, 20161001, Volume:
69
Journal Article
Peer reviewed
•Orienting attention in space enables effective perception and action.•Orienting of attention is sometimes reported to be affected by healthy aging.•Aging effects on orienting are specific to certain ...task, cue, and timing conditions.•Aging effects on orienting may be a function of ancillary cognitive factors.•Multiple brain substrates of orienting may explain the diversity of aging effects.
Changes in attention are among the most important cognitive shifts associated with aging, with implications for maintenance of vocational competencies, participation in social interactions, and successful execution of activities of daily living. An important facet of attention is orienting, the ability to selectively attend a location or modality and thereby engender perceptual augmentation. Orienting also involves shifting of the focus of attention in response to unanticipated salient events. Aging may impact orienting through a variety of neurocognitive mechanisms and the interactions between them. We review findings regarding factors that mediate the impact of aging on orienting, including overt vs. covert attending, exogenous vs. endogenous processes, orienting benefits vs. reorienting costs, cue-target onset asynchrony (SOA), post-orienting task factors, and stage of aging. We also consider aging-related changes in the brain substrates of orienting, including cortical and white matter integrity, laterality, connectivity, neuromodulatory functions, and compensatory activity. Taken together, these findings suggest that healthy aging impacts performance on orienting tasks less through direct effects than via interactions with additional cognitive processes.
Nuclear shape influences cell migration, gene expression and cell cycle progression, and is altered in disease states like laminopathies and cancer. What factors and forces determine nuclear shape? ...We find that nuclei assembled in Xenopus egg extracts in the presence of dynamic F-actin exhibit a striking bilobed nuclear morphology with distinct membrane compositions in the two lobes and accumulation of F-actin at the inner nuclear envelope. The addition of Lamin A (encoded by lmna), which is absent from Xenopus eggs, results in rounder nuclei, suggesting that opposing nuclear F-actin and Lamin A forces contribute to the regulation of nuclear shape. Nuclear F-actin also promotes altered nuclear shape in Lamin A-knockdown HeLa cells and, in both systems, abnormal nuclear shape is driven by formins and not Arp2/3 or myosin. Although the underlying mechanisms might differ in Xenopus and HeLa cells, we propose that nuclear F-actin filaments nucleated by formins impart outward forces that lead to altered nuclear morphology unless Lamin A is present. Targeting nuclear actin dynamics might represent a novel approach to rescuing disease-associated defects in nuclear shape.
Punishment as a response to impairment of individual or group welfare may be found not only among humans but also among a wide range of social animals. In some cases, acts of punishment serve to ...increase social cooperation among conspecifics. Such phenomena motivate the search for the biological foundations of punishment among humans. Of special interest are cases of pro-social punishment of individuals harming others. Behavioral studies have shown that in economic games people punish exploiters even at a cost to their own welfare. Additionally, neuroimaging studies have reported activity during the planning of such punishment in brain areas involved in the anticipation of reward. Such findings hint that there is an evolutionarily honed basic drive to punish social offenders. I argue that the transfer of punishment authority from the individual to the group requires that social offenders be punished as a public good, even if such punishment is not effective as retribution or deterrent. Furthermore, the social need for punishment of offenders has implications for alternatives to incarceration, publicity of punishment, and judicial structure.
Sizes of intracellular structures are important for function, yet mechanisms underlying subcellular size control are largely unexplored. A new study reveals how differences in tubulin populations ...between two related Xenopus frog species influence microtubule dynamics and spindle length.
Sizes of intracellular structures are important for function, yet mechanisms underlying subcellular size control are largely unexplored. A new study reveals how differences in tubulin populations between two related Xenopus frog species influence microtubule dynamics and spindle length.
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