Blending Learning: The Evolution of Online and Face-to-Face Education from 20082015

In 2008, iNACOL produced a series of papers documenting promising practices identified throughout the field of K–12 online learning. Since then, we have witnessed a tremendous acceleration of transformative policy and practice driving personalized learning in the K–12 education space. State, district, school, and classroom leaders recognize that the ultimate potential for blended and online learning lies in the opportunity to transform the education system and enable higher levels of learning through competency-based approaches.iNACOL's core work adds significant value to the field by providing a powerful practitioner voice in policy advocacy, communications, and in the creation of resources and best practices to enable transformational change in K–12 education.We worked with leaders throughout the field to update these resources for a new generation of pioneers working towards the creation of student-centered learning environments.This refreshed series, Promising Practices in Blended and Online Learning, explores some of the approaches developed by practitioners and policymakers in response to key issues in K–12 education, including:Blended Learning: The Evolution of Online and Face-to-Face Education from 2008-2015;Using Blended and Online Learning for Credit Recovery and At-Risk Students;Oversight and Management of Blended and Online Programs: Ensuring Quality and Accountability; andFunding and Legislation for Blended and Online Education.Personalized learning environments provide the very best educational opportunities and personalized pathways for all students, with highly qualified teachers delivering world-class instruction using innovative digital resources and content. Through this series of white papers, we are pleased to share the promising practices in K–12 blended, online, and competency education transforming teaching and learning today

Dss1 is a 26S proteasome ubiquitin receptor

The ubiquitin-proteasome system is the major pathway for protein degradation in eukaryotic cells. Proteins to be degraded are conjugated to ubiquitin chains that act as recognition signals for the 26S proteasome. The proteasome subunits Rpn10 and Rpn13 are known to bind ubiquitin, but genetic and biochemical data suggest the existence of at least one other substrate receptor. Here, we show that the phylogenetically conserved proteasome subunit Dss1 (Sem1) binds ubiquitin chains linked by K63 and K48. Atomic resolution data show that Dss1 is disordered and binds ubiquitin by binding sites characterized by acidic and hydrophobic residues. The complementary binding region in ubiquitin is composed of a hydrophobic patch formed by I13, I44, and L69 flanked by two basic regions. Mutations in the ubiquitin-binding site of Dss1 cause growth defects and accumulation of ubiquitylated proteins

From START to FINISH : the influence of osmotic stress on the cell cycle

Peer reviewedPublisher PD

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

Fighting viral infections and virus-driven tumors with cytotoxic CD4+ T cells

CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors

Between “Voluntary Migrants” and War Refugees: The Health of the Shan Burmese Migrant Workers in Northern Thailand

The Shan are a large migrant group from Burma (Myanmar) found within Thailand. While some Shan migrate to escape the civil war within Burma, others migrate for economic opportunity. Despite the size of this population, little is known about their health. Our study highlights the need for expanded access to primary care among this Shan population. Despite the arduous and trying journeys of these Shan migrants, they do not display the level of health sometimes attributed to health selection among immigrant groups

The caspase-3-p120-RasGAP module generates a NF-κB repressor in response to cellular stress.

The nuclear factor κB (NF-κB) transcription factor is a master regulator of inflammation. Short-term NF-κB activation is generally beneficial. However, sustained NF-κB might be detrimental, directly causing apoptosis of cells or leading to a persistent damaging inflammatory response. NF-κB activity in stressed cells needs therefore to be controlled for homeostasis maintenance. In mildly stressed cells, caspase-3 cleaves p120 RasGAP, also known as RASA1, into an N-terminal fragment, which we call fragment N. We show here that this fragment is a potent NF-κB inhibitor. Fragment N decreases the transcriptional activity of NF-κB by promoting its export from the nucleus. Cells unable to generate fragment N displayed increased NF-κB activation upon stress. Knock-in mice expressing an uncleavable p120 RasGAP mutant showed exaggerated NF-κB activation when their epidermis was treated with anthralin, a drug used for the treatment of psoriasis. Our study provides biochemical and genetic evidence of the importance of the caspase-3-p120-RasGAP stress-sensing module in the control of stress-induced NF-κB activation

The future of evapotranspiration : global requirements for ecosystem functioning, carbon and climate feedbacks, agricultural management, and water resources

The fate of the terrestrial biosphere is highly uncertain given recent and projected changes in climate. This is especially acute for impacts associated with changes in drought frequency and intensity on the distribution and timing of water availability. The development of effective adaptation strategies for these emerging threats to food and water security are compromised by limitations in our understanding of how natural and managed ecosystems are responding to changing hydrological and climatological regimes. This information gap is exacerbated by insufficient monitoring capabilities from local to global scales. Here, we describe how evapotranspiration (ET) represents the key variable in linking ecosystem functioning, carbon and climate feedbacks, agricultural management, and water resources, and highlight both the outstanding science and applications questions and the actions, especially from a space-based perspective, necessary to advance them