PR-Set7 is Degraded in a Conditional Cul4A Transgenic Mouse Model of Lung Cancer.

BackgroundMaintenance of genomic integrity is essential to ensure normal organismal development and to prevent diseases such as cancer. PR-Set7 (also known as Set8) is a cell cycle regulated enzyme that catalyses monomethylation of histone 4 at Lys20 (H4K20me1) to promote chromosome condensation and prevent DNA damage. Recent studies show that CRL4CDT2-mediated ubiquitylation of PR-Set7 leads to its degradation during S phase and after DNA damage. This might occur to ensure appropriate changes in chromosome structure during the cell cycle or to preserve genome integrity after DNA damage.MethodsWe developed a new model of lung tumor development in mice harboring a conditionally expressed allele of Cul4A. We have therefore used a mouse model to demonstrate for the first time that Cul4A is oncogenic in vivo. With this model, staining of PR-Set7 in the preneoplastic and tumor lesions in AdenoCre-induced mouse lungs was performed. Meanwhile we identified higher protein level changes of γ-tubulin and pericentrin by IHC.ResultsThe level of PR-Set7 down-regulated in the preneoplastic and adenocarcinomous lesions following over-expression of Cul4A. We also identified higher levels of the proteins pericentrin and γ-tubulin in Cul4A mouse lungs induced by AdenoCre.ConclusionsPR-Set7 is a direct target of Cul4A for degradation and involved in the formation of lung tumors in the conditional Cul4A transgenic mouse model

Lifetime Earnings Variability and Retirement Wealth

This paper explores how earnings variability is related to retirement wealth. Past research has demonstrated that the average American household on the verge of retirement would need to save substantially more, in order to preserve consumption flows in old age. While several socioeconomic factors have been examined that might explain such problems, prior studies have not assessed the role of earnings variability over the lifetime as a potential explanation for poor retirement prospects. Thus two workers having identical levels of average lifetime earnings might have had very different patterns of earnings variability over their lifetimes. Such differences could translate into quite different retirement wealth outcomes. This paper evaluates the effect of earnings variability on retirement wealth using information supplied by respondents to the Health and Retirement Study (HRS). This is a rich and nationally representative dataset on Americans on the verge of retirement, with responses linked to administrative records from the Social Security Administration. Our research illuminates the key links between lifetime earnings variability and retirement wealth.

Electrodynamics of Media

Contains reports on four research projects.Joint Services Electronics Program (Contract DAAB07-76-C-1400)California Institute of Technology (Contract 953524)National Science Foundation (Grant ENG76-01654)National Aeronautics and Space Administration (Contract NAS5-24139

Electrodynamics of Media

Contains research objectives and summary of research.Joint Services Electronics Program (Contract DAAB07-71-C-0300)California Institute of Technology (Contract 953524

Ethical perspectives on advances in biogerontology

Worldwide populations are aging with economic development as a result of public health initiatives and advances in therapeutic discoveries. Since 1850, life expectancy has advanced by 1 year for every four. Accompanying this change is the rapid development of anti‐aging science. There are three schools of thought in the field of aging science. One perspective is the life course approach, which considers that aging is a good and natural process to be embraced as a necessary and positive aspect of life, where the aim is to improve the quality of existing lifespan and “compress” morbidity. Another view is that aging is undesirable, and that rejuvenation and indeed immortality are possible since the biological basis of aging is understood, and therefore, strategies are possible for engineering negligible senescence. Finally, a hybrid approach is that life span can be extended by anti‐aging medicines but with uncertain effects on health. While these advances offer much promise, the ethical perspectives are seldom discussed in cross‐disciplinary settings. This article discusses some of the key ethical issues arising from recent advances in biogerontology

Distinct mechanisms of Drosophila CRYPTOCHROME-mediated light-evoked membrane depolarization and in vivo clock resetting.

Drosophila CRYPTOCHROME (dCRY) mediates electrophysiological depolarization and circadian clock resetting in response to blue or ultraviolet (UV) light. These light-evoked biological responses operate at different timescales and possibly through different mechanisms. Whether electron transfer down a conserved chain of tryptophan residues underlies biological responses following dCRY light activation has been controversial. To examine these issues in in vivo and in ex vivo whole-brain preparations, we generated transgenic flies expressing tryptophan mutant dCRYs in the conserved electron transfer chain and then measured neuronal electrophysiological phototransduction and behavioral responses to light. Electrophysiological-evoked potential analysis shows that dCRY mediates UV and blue-light-evoked depolarizations that are long lasting, persisting for nearly a minute. Surprisingly, dCRY appears to mediate red-light-evoked depolarization in wild-type flies, absent in both cry-null flies, and following acute treatment with the flavin-specific inhibitor diphenyleneiodonium in wild-type flies. This suggests a previously unsuspected functional signaling role for a neutral semiquinone flavin state (FADH•) for dCRY. The W420 tryptophan residue located closest to the FAD-dCRY interaction site is critical for blue- and UV-light-evoked electrophysiological responses, while other tryptophan residues within electron transfer distance to W420 do not appear to be required for light-evoked electrophysiological responses. Mutation of the dCRY tryptophan residue W342, more distant from the FAD interaction site, mimics the cry-null behavioral light response to constant light exposure. These data indicate that light-evoked dCRY electrical depolarization and clock resetting are mediated by distinct mechanisms

A review of the trend of microlearning

Purpose Microlearning has been considered as a promising topic in work-based learning. This paper aims to review the trends of microlearning in terms of related publications and internet searches. Hopefully, the findings can serve as a reference for the education sector, government, business and academia, to promote, design and use microlearning. Design/methodology/approach In this study, two sets of analysis were conducted. Firstly, we analysed the publication trend of microlearning. Second, we analysed the trend of internet searches related to microlearning. More specifically, we analysed 14-years real-world data obtained from Scopus and Google Trends for the purpose. These data include the first relevant publication found in the database. Findings In total, 476 relevant publication have been identified during 2006 to 2019. According to the findings from analysing the identified publications, microlearning is a relevant new and emerging global topic involving authors, affiliations and funding sponsors from different countries. Moreover, many microlearning related publications were conducted from perspectives of elearning or mobile learning. Furthermore, we notice higher education was the most frequently mentioned education level in the identified publications. On the other hand, language learning (i.e. second language, vocabulary learning) had been mentioned more times in the titles and abstracts then other subject areas. Overall, the increasing trend of publications on ‘microlearning’ (as a knowledge supply) is in line with the established increasing internet searches of ‘microlearning’ (as a practical demand) in recent years. Practical implications From the work-based learning perspective, microlearning has been considered as one of the key topics in talent development topics. Policymakers, educators, researchers and participators, have the responsibility to explore how to promote, design and use microlearning to help people to learn in the right direction through valid knowledge with ethical consideration. Originality/value Although many works had been done on microlearning, there is a lack of comprehensive studies reviewing the trends of microlearning in terms of related publications and internet searches. This study aims to fill this gap by analysing real-world data obtained from Scopus and Google Trends - these data include the first relevant publication found in the database. We believe this is the first time that a study has been conducted to comprehensively review the development trends of microlearning. Hopefully, this study can shed some light on related research

Electrodynamics of Media

Contains reports on three research projects.Joint Services Electronics Program (Contract DAAB07-75-C-1346

Distinctive Mechanisms and Patterns of Exudative Versus Tractional Intraretinal Cystoid Spaces as Seen With Multimodal Imaging.

PurposeTo determine clear-cut distinctions between tractional and exudative intraretinal cystoid spaces subtypes.DesignRetrospective, multicenter, observational case series.MethodsA cohort of patients diagnosed with intraretinal cystoid spaces and imaged with optical coherence tomography (OCT), fluorescein angiography (FA), blue fundus autofluorescence (BFAF), en face OCT, and OCT angiography (OCT-A) was included in the study. All images were qualitatively and quantitatively evaluated.ResultsIn this study were included 72 eyes of 69 patients. Exudative intraretinal cystoid spaces (36/72 eyes, 50%) displayed a "petaloid" morphology as seen with en face OCT, FA, and BFAF. Tractional intraretinal cystoid spaces (24/72 eyes, 33.3%), displayed a radial "spoke-wheel" en face OCT pattern. There was no leakage with FA and BFAF did not reveal specific patterns. Eyes with full-thickness macular hole (FTMH, 12/72 eyes, 16.7%) displayed a "sunflower" en face OCT appearance. FTMH showed OCT, OCT-A, and BFAF features of both exudative and tractional cystoid spaces, but without any FA leakage. Inner nuclear layer (INL) thickness was significantly lower in tractional cystoid spaces (P < .001). There were a greater number of INL cystoid spaces in both the exudative and FTMH subgroups (P = .001). The surface area of INL cystoid spaces was significantly lower in the tractional subgroup (P < .001). There was a significant reduction of the microvascular density in eyes with exudative vs tractional (P = .002) and FTMH (P < .001) subgroups.ConclusionsExudative and tractional intraretinal cystoid spaces displayed characteristic multimodal imaging features and they may represent 2 different pathologic conditions with equally different clinical implications