Temporal Proteome and Lipidome Profiles Reveal Hepatitis C Virus-Associated Reprogramming of Hepatocellular Metabolism and Bioenergetics

Proteomic and lipidomic profiling was performed over a time course of acute hepatitis C virus (HCV) infection in cultured Huh-7.5 cells to gain new insights into the intracellular processes influenced by this virus. Our proteomic data suggest that HCV induces early perturbations in glycolysis, the pentose phosphate pathway, and the citric acid cycle, which favor host biosynthetic activities supporting viral replication and propagation. This is followed by a compensatory shift in metabolism aimed at maintaining energy homeostasis and cell viability during elevated viral replication and increasing cellular stress. Complementary lipidomic analyses identified numerous temporal perturbations in select lipid species (e.g. phospholipids and sphingomyelins) predicted to play important roles in viral replication and downstream assembly and secretion events. The elevation of lipotoxic ceramide species suggests a potential link between HCV-associated biochemical alterations and the direct cytopathic effect observed in this in vitro system. Using innovative computational modeling approaches, we further identified mitochondrial fatty acid oxidation enzymes, which are comparably regulated during in vitro infection and in patients with histological evidence of fibrosis, as possible targets through which HCV regulates temporal alterations in cellular metabolic homeostasis

Host Genetics and HIV-1: The Final Phase?

This is a crucial transition time for human genetics in general, and for HIV host genetics in particular. After years of equivocal results from candidate gene analyses, several genome-wide association studies have been published that looked at plasma viral load or disease progression. Results from other studies that used various large-scale approaches (siRNA screens, transcriptome or proteome analysis, comparative genomics) have also shed new light on retroviral pathogenesis. However, most of the inter-individual variability in response to HIV-1 infection remains to be explained: genome resequencing and systems biology approaches are now required to progress toward a better understanding of the complex interactions between HIV-1 and its human host

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Control of Flowering and Cell Fate by LIF2, an RNA Binding Partner of the Polycomb Complex Component LHP1

Polycomb Repressive Complexes (PRC) modulate the epigenetic status of key cell fate and developmental regulators in eukaryotes. The chromo domain protein LIKE HETEROCHROMATIN PROTEIN1 (LHP1) is a subunit of a plant PRC1-like complex in Arabidopsis thaliana and recognizes histone H3 lysine 27 trimethylation, a silencing epigenetic mark deposited by the PRC2 complex. We have identified and studied an LHP1-Interacting Factor2 (LIF2). LIF2 protein has RNA recognition motifs and belongs to the large hnRNP protein family, which is involved in RNA processing. LIF2 interacts in vivo, in the cell nucleus, with the LHP1 chromo shadow domain. Expression of LIF2 was detected predominantly in vascular and meristematic tissues. Loss-of-function of LIF2 modifies flowering time, floral developmental homeostasis and gynoecium growth determination. lif2 ovaries have indeterminate growth and produce ectopic inflorescences with severely affected flowers showing proliferation of ectopic stigmatic papillae and ovules in short-day conditions. To look at how LIF2 acts relative to LHP1, we conducted transcriptome analyses in lif2 and lhp1 and identified a common set of deregulated genes, which showed significant enrichment in stress-response genes. By comparing expression of LHP1 targets in lif2, lhp1 and lif2 lhp1 mutants we showed that LIF2 can either antagonize or act with LHP1. Interestingly, repression of the FLC floral transcriptional regulator in lif2 mutant is accompanied by an increase in H3K27 trimethylation at the locus, without any change in LHP1 binding, suggesting that LHP1 is targeted independently from LIF2 and that LHP1 binding does not strictly correlate with gene expression. LIF2, involved in cell identity and cell fate decision, may modulate the activity of LHP1 at specific loci, during specific developmental windows or in response to environmental cues that control cell fate determination. These results highlight a novel link between plant RNA processing and Polycomb regulation

A buccaneer's atlas: Basil Ringrose's South Sea waggoner: a sea atlas and sailing directions of the Pacific coast of the Americas, 1682

On July 29, 1681, a band of English buccaneers that had been terrorizing Spanish possessions on the west coast of the Americas captured a Spanish ship, from which they obtained a derrotero , or book of charts and sailing directions. When they arrived back in England, the Spanish ambassador demanded that the buccaneers be brought to trial. The derrotero was ordered to be brought to King Charles II, who apparently appreciated its great intelligence value. The buccaneers were acquitted, to the chagrin of the king of Spain, who had the English ambassador expelled from the court at Madrid on a seemingly trumped-up charge.The derrotero was subsequently translated, and one of the buccaneers, Basil Ringrose, added a text to the compilation and information to the Spanish charts. The resulting atlas, consisting of 106 pages of charts and 106 pages of text, is published in full for the first time in this volume. Covering the coast from California to Tierra del Fuego, the Galapagos, and Juan Fernandes, Basil Ringrose's south sea waggoner is a rich source of geographical information, with observations on navigational, physical, biological, and cultural features as well as on ethnography, customs, and folklore.After almost exactly three hundred years, this secret atlas is now made available to libraries and individuals. The editors have provided an extensive introduction on historical, geographical, and navigational aspects of the atlas, as well as annotations to the charts and text, and they have plotted the coverage of the charts on modern map bases

Normative cruelties and gender deviants : the performative effects of bully discourses for girls and boys in school

Since the 1990s the educational community has witnessed a proliferation of ‘bullying’ discourses, primarily within the field of educational developmental social psychology. Drawing on ethnographic and qualitative interview data of primary and secondary school girls and boys, this article argues that the discourse ‘bullying’ operates to simplify and individualise complex gendered/classed/sexualised/racialised power relations embedded in children’s school‐based cultures. Using a feminist post‐structural approach, this article critically traces the discursive production of how the signifiers ‘bully’ and ‘victim’ are implicated in the ‘normative cruelties’ of performing and policing ‘intelligible’ heteronormative masculinities and femininities. It shows how these everyday gender performances are frequently passed over by staff and pupils as ‘natural’. The analysis also illustrates how bully discourses operate in complex racialised and classed ways that mark children out as either gender deviants, or as not adequately performing normative ideals of masculinity and femininity. In conclusion, it is argued that bully discourses offer few symbolic resources and/or practical tools for addressing and coping with everyday school‐based gender violence, and some new research directions are suggested