Formation of the postmitotic nuclear envelope from extended ER cisternae precedes nuclear pore assembly

During mitosis, the nuclear envelope merges with the endoplasmic reticulum (ER), and nuclear pore complexes are disassembled. In a current model for reassembly after mitosis, the nuclear envelope forms by a reshaping of ER tubules. For the assembly of pores, two major models have been proposed. In the insertion model, nuclear pore complexes are embedded in the nuclear envelope after their formation. In the prepore model, nucleoporins assemble on the chromatin as an intermediate nuclear pore complex before nuclear envelope formation. Using live-cell imaging and electron microscope tomography, we find that the mitotic assembly of the nuclear envelope primarily originates from ER cisternae. Moreover, the nuclear pore complexes assemble only on the already formed nuclear envelope. Indeed, all the chromatin-associated Nup 107–160 complexes are in single units instead of assembled prepores. We therefore propose that the postmitotic nuclear envelope assembles directly from ER cisternae followed by membrane-dependent insertion of nuclear pore complexes

Web Workouts and consumer well-being: The role of digital-physical activity during the UK COVID-19 lockdown

By using three areas of well-being, psychological, physical and social (Grant, Christianson and Price, 2007) this study aims to explore the perceptions of consumers engaging in digital-physical platforms and communities during the UK COVID-19 lockdown and the impact such participation had on their well-being. 90 people were recruited via an online study, all were using online workouts, and self-selected to participate. The use of virtual ethnography gave a further insight into the functions of these platforms and their role in social connection. Participants discussed the benefits to their mental health, the provision of structure to their day, the social connection it provided and the alleviation of feelings of isolation. The findings also demonstrate how numerous consumer groups in society could use digital-physical platforms as a potential way of connecting those who are unable to engage in face-to-face settings

Near surface properties of mixtures of propylammonium nitrate with n-alkanols 1. Nanostructure

In situ amplitude modulated-atomic force microscopy (AM-AFM) has been used to probe the nanostructure of mixtures of propylammonium nitrate (PAN) with n-alkanols near a mica surface. PAN is a protic ionic liquid (IL) which has a bicontinuous sponge-like nanostructure of polar and apolar domains in the bulk, which becomes flatter near a solid surface. Mixtures of PAN with 1-butanol, 1-octanol, and 1-dodecanol at 10–70 vol% n-alkanol have been examined, along with each pure n-alkanol, to reveal the effect of composition and n-alkanol chain length. At low concentrations the butanol simply swells the PAN near-surface nanostructure, but at higher concentrations the nanostructure fragments. Octanol and dodecanol first lower the preferred curvature of the PAN near-surface nanostructure because, unlike n-butanol, their alkyl chains are too long to be accommodated alongside the PAN cations. At higher concentrations, octanol and dodecanol self-assemble into n-alkanol rich aggregates in a PAN rich matrix. The concentration at which aggregation first becomes apparent decreases with n-alkanol chain length

Nucleocytoplasmic transport: a thermodynamic mechanism

The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.Comment: in press at HFSP Journal, vol 3 16 text pages, 1 table, 4 figures, plus Supplementary Material include

Political Branding: The Tea Party and Its Use of Participation Branding

The emergence of the Tea Party movement in 2009 witnessed the surfacing of a populist, anti-Obama libertarian mobilization within the United States. The Tea Party, a movement that brought together a number of disparate groups—some new, some established—utilized participation branding where the consumer attributed the movement its own identity and brand. Its consumer-facing approach, lack of one single leader, and lack of a detailed party platform, in combination with its impact on the 2010 election races in America, earmarks it as a contemporary and unconventional brand phenomenon worthy of investigation. Copyright © Taylor & Francis Group, LLC

Eosinophils Are Recruited in Response to Chitin Exposure and Enhance Th2-Mediated Immune Pathology in Aspergillus fumigatus Infection

In patients infected with the fungus Aspergillus fumigatus, Th1 responses are considered protective, while Th2 responses are associated with increased morbidity and mortality. How host-pathogen interactions influence the development of these protective or detrimental immune responses is not clear. We compared lung immune responses to conidia from two fungal isolates that expressed different levels of the fungal cell wall component chitin. We observed that repeated aspirations of the high-chitin-expressing isolate Af5517 induced increased airway eosinophilia in the lungs of recipient mice compared to the level of eosinophilia induced by isolate Af293. CD4+ T cells in the bronchoalveolar lavage fluid (BALF) of Af5517-aspirated mice displayed decreased gamma interferon secretion and increased interleukin-4 transcription. In addition, repeated aspirations of Af5517 induced lung transcription of the Th2-associated chemokines CCL11 (eotaxin-1) and CCL22 (macrophage-derived chemokine). Eosinophil recruitment in response to conidial aspiration was correlated with the level of chitin exposure during germination and was decreased by constitutive lung chitinase expression. Moreover, eosinophil-deficient mice subjected to multiple aspirations of Af5517 prior to neutrophil depletion and infection exhibited decreased morbidity and fungal burden compared to the levels of morbidity and fungal burden found in wild-type mice. These results suggest that exposure of chitin in germinating conidia promotes eosinophil recruitment and ultimately induces Th2-skewed immune responses after repeated aspiration. Furthermore, our results suggest that eosinophils should be examined as a potential therapeutic target in patients that mount poorly protective Th2 responses to A. fumigatus infection

Involvement in surface antigen expression by a moonlighting FG-repeat nucleoporin in trypanosomes

Components of the nuclear periphery coordinate a multitude of activities, including macromolecular transport, cell-cycle progression, and chromatin organization. Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport, mRNA processing, and transcriptional regulation, and NPC components can define regions of high transcriptional activity in some organisms at the nuclear periphery and nucleoplasm. Lineage-specific features underpin several core nuclear functions and in trypanosomatids, which branched very early from other eukaryotes, unique protein components constitute the lamina, kinetochores, and parts of the NPCs. Here we describe a phenylalanine-glycine (FG)-repeat nucleoporin, TbNup53b, that has dual localizations within the nucleoplasm and NPC. In addition to association with nucleoporins, TbNup53b interacts with a known trans-splicing component, TSR1, and has a role in controlling expression of surface proteins including the nucleolar periphery-located, procyclin genes. Significantly, while several nucleoporins are implicated in intranuclear transcriptional regulation in metazoa, TbNup53b appears orthologous to components of the yeast/human Nup49/Nup58 complex, for which no transcriptional functions are known. These data suggest that FG-Nups are frequently co-opted to transcriptional functions during evolution and extend the presence of FG-repeat nucleoporin control of gene expression to trypanosomes, suggesting that this is a widespread and ancient eukaryotic feature, as well as underscoring once more flexibility within nucleoporin function

ALADIN is Required for the Production of Fertile Mouse Oocytes

Asymmetric cell divisions depend on the precise placement of the spindle apparatus. In mammalian oocytes, spindles assemble close to the cell's center, but chromosome segregation takes place at the cell periphery where half of the chromosomes are expelled into small, nondeveloping polar bodies at anaphase. By dividing so asymmetrically, most of the cytoplasmic content within the oocyte is preserved, which is critical for successful fertilization and early development. Recently we determined that the nucleoporin ALADIN participates in spindle assembly in somatic cells, and we have also shown that female mice homozygously null for ALADIN are sterile. In this study we show that this protein is involved in specific meiotic stages, including meiotic resumption, spindle assembly, and spindle positioning. In the absence of ALADIN, polar body extrusion is compromised due to problems in spindle orientation and anchoring at the first meiotic anaphase. ALADIN null oocytes that mature far enough to be fertilized in vitro are unable to support embryonic development beyond the two-cell stage. Overall, we find that ALADIN is critical for oocyte maturation and appears to be far more essential for this process than for somatic cell divisions

Pore timing:the evolutionary origins of the nucleus and nuclear pore complex

The name “eukaryote” is derived from Greek, meaning “true kernel”, and describes the domain of organisms whose cells have a nucleus. The nucleus is thus the defining feature of eukaryotes and distinguishes them from prokaryotes (Archaea and Bacteria), whose cells lack nuclei. Despite this, we discuss the intriguing possibility that organisms on the path from the first eukaryotic common ancestor to the last common ancestor of all eukaryotes did not possess a nucleus at all—at least not in a form we would recognize today—and that the nucleus in fact arrived relatively late in the evolution of eukaryotes. The clues to this alternative evolutionary path lie, most of all, in recent discoveries concerning the structure of the nuclear pore complex. We discuss the evidence for such a possibility and how this impacts our views of eukaryote origins and how eukaryotes have diversified subsequent to their last common ancestor

Mothers doing doctorates part-time – why do we make it harder than it needs to be?

If universities really want mature students with families to succeed they’ll need to completely rethink the traditional image of the “doctoral student”. Widening access isn’t enough, say Sue Cronshaw, Peter Stokes, and Alistair McCulloch. Doing a PhD is hard. It’s hard even when everything goes right with your research project and it’s hard even when everything is set up to support you through three years of full-time study. Put simply, it’s hard because it involves an intensive period of what has been called the ‘highest learning’ and because it involves mastering the advanced knowledge and skills necessary to be welcomed into the relevant disciplinary community. It’s hard because learning and managing a long term-project is hard. But doing a PhD is even harder if study is undertaken on a part-time basis (completion rates for part-time PhD students are woefully low), and if there are social and personal barriers that have to be overcome in addition to the requirements of high-level research learning and research writing. Because public and institutional policy and institutional process are designed largely on the basis of the stereotypical “traditional” student (young, full-time, and without dependents), studying as a “non-traditional” student may not be easy