Relaunching Nurses to the Forefront of the COVID-19 Pandemic: Heeding the Call Through an RN Refresher Program.

Nursing remains the largest health care profession in the nation and RNs comprise one of the largest segments of the U.S. workforce with just under 4 million RNs nationwide. Despite the large number of nurses in practice, a variety of factors contribute to the availability of RNs able to meet health care-related demands, leading out-of-practice nurses to seek reentry into the workforce. To develop the skills and knowledge needed to deliver safe and effective care, nurses seeking to return to practice need access to formally structured continuing education opportunities. Nursing refresher courses have historically filled this gap, effectively supporting the reemployment of nurses by preparing them for clinical practice. The COVID-19 pandemic is among the most recent factors encouraging nurse reentry, thus furthering the need for continuing education in support of license renewal. This article provides insight into the development of a university-based refresher program for Texas nurses seeking to reactivate licensure and gain the theoretical and clinical knowledge needed to return to nursing considering the health care demands produced by this unprecedented crisis. [J Contin Educ Nurs. 2021;52(2)67-71.].

c-Abl phosphorylation of Yin Yang 1's conserved tyrosine 254 in the spacer region modulates its transcriptional activity.

Yin Yang 1 (YY1) is a multifunctional transcription factor that can activate or repress transcription depending on the promotor and/or the co-factors recruited. YY1 is phosphorylated in various signaling pathways and is critical for different biological functions including embryogenesis, apoptosis, proliferation, cell-cycle regulation and tumorigenesis. Here we report that YY1 is a substrate for c-Abl kinase phosphorylation at conserved residue Y254 in the spacer region. Pharmacological inhibition of c-Abl kinase by imatinib, nilotinib and GZD824, knock-down of c-Abl using siRNA, and the use of c-Abl kinase-dead drastically reduces tyrosine phosphorylation of YY1. Both radioactive and non-radioactive in vitro kinase assays, as well as co-immunoprecipitation in different cell lines, show that the target of c-Abl phosphorylation is tyrosine residue 254. c-Abl phosphorylation has little effect on YY1 DNA binding ability or cellular localization in asynchronous cells. However, functional studies reveal that c-Abl mediated phosphorylation of YY1 regulates YY1's transcriptional ability in vivo. In conclusion, we demonstrate the novel role of c-Abl kinase in regulation of YY1's transcriptional activity, linking YY1 regulation with c-Abl tyrosine kinase signaling pathways.

Deriving Information Requirements for a Smart Nursing System for Intensive Care Units.

The workplace environment for intensive care nursing is highly stressful, with long working hours and a dynamic workload that may induce fatigue. The resulting stress and fatigue may reduce nurses' efficiency and may contribute to medical errors. A smart wearable system is being designed to help nurses who experience high levels of stress and fatigue at work. This article documents the systematic process of deriving information requirements from 2 focus groups conducted separately with nurses and nurse managers working in various Southeastern Texas hospitals. While nurses expected functionality such as memory aid tools, health assessment, and stress-reducing exercises, nurse managers expected information about the overall status of the unit's fatigue/stress levels as well as nurses' communication and movement patterns. The derived information requirements will act as an objective assessment of needs and would set the stage for the design of a stress-monitoring tool.

Aurora A Phosphorylation of YY1 during Mitosis Inactivates its DNA Binding Activity.

Successful execution of mitotic cell division requires the tight synchronisation of numerous biochemical pathways. The underlying mechanisms that govern chromosome segregation have been thoroughly investigated. However, the mechanisms that regulate transcription factors in coordination with mitotic progression remain poorly understood. In this report, we identify the transcription factor YY1 as a novel mitotic substrate for the Aurora A kinase, a key regulator of critical mitotic events, like centrosome maturation and spindle formation. Using in vitro kinase assays, we show that Aurora A directly phosphorylates YY1 at serine 365 in the DNA-binding domain. Using a new phospho-specific antibody, we show that YY1 phosphorylation at serine 365 occurs during mitosis, and that this phosphorylation is significantly reduced upon inhibition of Aurora A. Furthermore, we show, using electrophoretic mobility shift and chromatin immunoprecipitation assays, that phosphorylation of YY1 at this site abolishes its DNA binding activity in vitro and in vivo. In conformity with this loss of binding activity, phosphorylated YY1 also loses its transctivation ability as demonstrated by a luciferase reporter assay. These results uncover a novel mechanism that implicates Aurora A in the mitotic inactivation of transcription factors.

Tambora and the mackerel year: Phenology and fisheries during an extreme climate event.

Global warming has increased the frequency of extreme climate events, yet responses of biological and human communities are poorly understood, particularly for aquatic ecosystems and fisheries. Retrospective analysis of known outcomes may provide insights into the nature of adaptations and trajectory of subsequent conditions. We consider the 1815 eruption of the Indonesian volcano Tambora and its impact on Gulf of Maine (GoM) coastal and riparian fisheries in 1816. Applying complex adaptive systems theory with historical methods, we analyzed fish export data and contemporary climate records to disclose human and piscine responses to Tambora's extreme weather at different spatial and temporal scales while also considering sociopolitical influences. Results identified a tipping point in GoM fisheries induced by concatenating social and biological responses to extreme weather. Abnormal daily temperatures selectively affected targeted fish species-alewives, shad, herring, and mackerel-according to their migration and spawning phenologies and temperature tolerances. First to arrive, alewives suffered the worst. Crop failure and incipient famine intensified fishing pressure, especially in heavily settled regions where dams already compromised watersheds. Insufficient alewife runs led fishers to target mackerel, the next species appearing in abundance along the coast; thus, 1816 became the "mackerel year." Critically, the shift from riparian to marine fisheries persisted and expanded after temperatures moderated and alewives recovered. We conclude that contingent human adaptations to extraordinary weather permanently altered this complex system. Understanding how adaptive responses to extreme events can trigger unintended consequences may advance long-term planning for resilience in an uncertain future.

Revisiting the logistic map: A closer look at the dynamics of a classic chaotic population model with ecologically realistic spatial structure and dispersal.

There is an ongoing debate about the applicability of chaotic and nonlinear models to ecological systems. Initial introduction of chaotic population models to the ecological literature was largely theoretical in nature and difficult to apply to real-world systems. Here, we build upon and expand prior work by performing an in-depth examination of the dynamical complexities of a spatially explicit chaotic population, within an ecologically applicable modeling framework. We pair a classic chaotic growth model (the logistic map) with explicit dispersal length scale and shape via a Gaussian dispersal kernel. Spatio-temporal heterogeneity is incorporated by applying stochastic perturbations throughout the spatial domain. We witness a variety of population dynamics dependent on the growth rate, dispersal distance, and domain size. Dispersal serves to eliminate chaotic population behavior for many of the parameter combinations tested. The model displays extreme sensitivity to changes in growth rate, dispersal distance, or domain size, but is robust to low-level stochastic population perturbations. Large and temporally consistent perturbations can lead to a change in population dynamics. Frequent switching occurs between chaotic/non-chaotic behaviors as dispersal distance, domain size, or growth rate increases. Small changes in these parameters are easy to imagine in real populations, and understanding or anticipating the abrupt resulting shifts in population dynamics is important for population management and conservation.

The transcription factor YY1 is a novel substrate for Aurora B kinase at G2/M transition of the cell cycle.

Yin Yang 1 (YY1) is a ubiquitously expressed and highly conserved multifunctional transcription factor that is involved in a variety of cellular processes. Many YY1-regulated genes have crucial roles in cell proliferation, differentiation, apoptosis, and cell cycle regulation. Numerous mechanisms have been shown to regulate the function of YY1, such as DNA binding affinity, subcellular localization, and posttranslational modification including phosphorylation. Polo-like kinase 1(Plk1) and Casein kinase 2α (CK2 α) were the first two kinases identified to phosphorylate YY1. In this study, we identify a third kinase. We report that YY1 is a novel substrate of the Aurora B kinase both in vitro and in vivo. Serine 184 phosphorylation of YY1 by Aurora B is cell cycle regulated and peaks at G2/M and is rapidly dephosphorylated, likely by protein phosphatase 1 (PP1) as the cells enter G1. Aurora A and Aurora C can also phosphorylate YY1 in vitro, but at serine/threonine residues other than serine 184. We present evidence that phosphorylation of YY1 in the central glycine/alanine (G/A)-rich region is important for DNA binding activity, with a potential phosphorylation/acetylation interplay regulating YY1 function. Given their importance in mitosis and overexpression in human cancers, Aurora kinases have been identified as promising therapeutic targets. Increasing our understanding of Aurora substrates will add to the understanding of their signaling pathways.

Phosphorylation of the transcription factor YY1 by CK2α prevents cleavage by caspase 7 during apoptosis.

In this report, we describe the phosphorylation of Yin Yang 1 (YY1) in vitro and in vivo by CK2α (casein kinase II), a multifunctional serine/threonine protein kinase. YY1 is a ubiquitously expressed multifunctional zinc finger transcription factor implicated in regulation of many cellular and viral genes. The products of these genes are associated with cell growth, the cell cycle, development, and differentiation. Numerous studies have linked YY1 to tumorigenesis and apoptosis. YY1 is a target for cleavage by caspases in vitro and in vivo as well, but very little is known about the mechanisms that regulate its cleavage during apoptosis. Here, we identify serine 118 in the transactivation domain of YY1 as the site of CK2α phosphorylation, proximal to a caspase 7 cleavage site. CK2α inhibitors, as well as knockdown of CK2α by small interfering RNA, reduce S118 phosphorylation in vivo and enhance YY1 cleavage under apoptotic conditions, whereas increased CK2α activity by overexpression in vivo elevates S118 phosphorylation. A serine-to-alanine substitution at serine 118 also increases the cleavage of YY1 during apoptosis compared to wild-type YY1. Taken together, we have discovered a regulatory link between YY1 phosphorylation at serine 118 and regulation of its cleavage during programmed cell death.

Global mitotic phosphorylation of C2H2 zinc finger protein linker peptides.

Cessation of transcriptional activity is a hallmark of cell division. Many biochemical pathways have been shown and proposed over the past few decades to explain the silence of this phase. In particular, many individual transcription factors have been shown to be inactivated by phosphorylation. In this report, we show the simultaneous phosphorylation and mitotic redistribution of a whole class of modified transcription factors. C(2)H(2) zinc finger proteins (ZFPs) represent the largest group of gene expression regulators in the human genome. Despite their diversity, C(2)H(2) ZFPs display striking conservation of small linker peptides joining their adjacent zinc finger modules. These linkers are critical for DNA binding activity. It has been proposed that conserved phosphorylation of these linker peptides could be a common mechanism for the inactivation of the DNA binding activity of C(2)H(2) ZFPs, during mitosis. Using a novel antibody, raised against the phosphorylated form of the most conserved linker peptide sequence, we are able to visualize the massive and simultaneous mitotic phosphorylation of hundreds of these proteins. We show that this wave of phosphorylation is tightly synchronized, starting in mid-prophase right after DNA condensation and before the breakdown of the nuclear envelope. This global phosphorylation is completely reversed in telophase. In addition, the exclusion of the phospho-linker signal from condensed DNA clearly demonstrates a common mechanism for the mitotic inactivation of C(2)H(2) ZFPs.

The transcription factor YY1 is a substrate for Polo-like kinase 1 at the G2/M transition of the cell cycle.

Yin-Yang 1 (YY1) is an essential multifunctional zinc-finger protein. It has been shown over the past two decades to be a critical regulator of a vast array of biological processes, including development, cell proliferation and differentiation, DNA repair, and apoptosis. YY1 exerts its functions primarily as a transcription factor that can activate or repress gene expression, dependent on its spatial and temporal context. YY1 regulates a large number of genes involved in cell cycle transitions, many of which are oncogenes and tumor-suppressor genes. YY1 itself has been classified as an oncogene and was found to be upregulated in many cancer types. Unfortunately, our knowledge of what regulates YY1 is very minimal. Although YY1 has been shown to be a phosphoprotein, no kinase has ever been identified for the phosphorylation of YY1. Polo-like kinase 1 (Plk1) has emerged in the past few years as a major cell cycle regulator, particularly for cell division. Plk1 has been shown to play important roles in the G/M transition into mitosis and for the proper execution of cytokinesis, processes that YY1 has been shown to regulate also. Here, we present evidence that Plk1 directly phosphorylates YY1 in vitro and in vivo at threonine 39 in the activation domain. We show that this phosphorylation is cell cycle regulated and peaks at G2/M. This is the first report identifying a kinase for which YY1 is a substrate.

Identification of G1-regulated genes in normally cycling human cells.

BACKGROUND: Obtaining synchronous cell populations is essential for cell-cycle studies. Methods such as serum withdrawal or use of drugs which block cells at specific points in the cell cycle alter cellular events upon re-entry into the cell cycle. Regulatory events occurring in early G1 phase of a new cell cycle could have been overlooked. METHODOLOGY AND FINDINGS: We used a robotic mitotic shake-off apparatus to select cells in late mitosis for genome-wide gene expression studies. Two separate microarray experiments were conducted, one which involved isolation of RNA hourly for several hours from synchronous cell populations, and one experiment which examined gene activity every 15 minutes from late telophase of mitosis into G1 phase. To verify synchrony of the cell populations under study, we utilized methods including BrdU uptake, FACS, and microarray analyses of histone gene activity. We also examined stress response gene activity. Our analysis enabled identification of 200 early G1-regulated genes, many of which currently have unknown functions. We also confirmed the expression of a set of genes candidates (fos, atf3 and tceb) by qPCR to further validate the newly identified genes. CONCLUSION AND SIGNIFICANCE: Genome-scale expression analyses of the first two hours of G1 in naturally cycling cells enabled the discovery of a unique set of G1-regulated genes, many of which currently have unknown functions, in cells progressing normally through the cell division cycle. This group of genes may contain future targets for drug development and treatment of human disease.

Identification of genes periodically expressed in the human cell cycle and their expression in tumors.

The genome-wide program of gene expression during the cell division cycle in a human cancer cell line (HeLa) was characterized using cDNA microarrays. Transcripts of >850 genes showed periodic variation during the cell cycle. Hierarchical clustering of the expression patterns revealed coexpressed groups of previously well-characterized genes involved in essential cell cycle processes such as DNA replication, chromosome segregation, and cell adhesion along with genes of uncharacterized function. Most of the genes whose expression had previously been reported to correlate with the proliferative state of tumors were found herein also to be periodically expressed during the HeLa cell cycle. However, some of the genes periodically expressed in the HeLa cell cycle do not have a consistent correlation with tumor proliferation. Cell cycle-regulated transcripts of genes involved in fundamental processes such as DNA replication and chromosome segregation seem to be more highly expressed in proliferative tumors simply because they contain more cycling cells. The data in this report provide a comprehensive catalog of cell cycle regulated genes that can serve as a starting point for functional discovery. The full dataset is available at http://genome-www.stanford.edu/Human-CellCycle/HeLa/.