Regulation of the retinoblastoma proteins by the human herpesviruses

Viruses are obligate intracellular parasites that alter the environment of infected cells in order to replicate more efficiently. One way viruses achieve this is by modulating cell cycle progression. The main regulators of progression out of G0, through G1, and into S phase are the members of the retinoblastoma (Rb) family of tumor suppressors. Rb proteins repress the transcription of genes controlled by the E2F transcription factors. Because the expression of E2F-responsive genes is required for cell cycle progression into the S phase, Rb arrests the cell cycle in G0/G1. A number of viral proteins directly target Rb family members for inactivation, presumably to create an environment more hospitable for viral replication. Such viral proteins include the extensively studied oncoproteins E7 (from human papillomavirus), E1A (from adenovirus), and the large T (tumor) antigen (from simian virus 40). Elucidating how these three viral proteins target and inactivate Rb has proven to be an invaluable approach to augment our understanding of both normal cell cycle progression and carcinogenesis. In addition to these proteins, a number of other virally-encoded inactivators of the Rb family have subsequently been identified including a surprising number encoded by human herpesviruses. Here we review how the human herpesviruses modulate Rb function during infection, introduce the individual viral proteins that directly or indirectly target Rb, and speculate about what roles Rb modulation by these proteins may play in viral replication, pathogenesis, and oncogenesis

Digestive plasticity of the small intestine and the fermentative hindgut in a marsupial herbivore, the tammar wallaby (Macropus eugenii)

We investigated the effects of a ground, pelleted diet versus natural forage on the gross morphology of the gastrointestinal tract of a medium- sized (5 - 7 kg body mass) macropodid marsupial, the tammar wallaby ( Macropus eugenii). The empty wet mass ( g) of the small intestine of tammar wallabies maintained on a pelleted diet for 6 weeks was 22% greater than that of animals maintained on natural forage, once body mass was taken into account by ANCOVA. Similarly, the body-mass-adjusted length of the tammar wallaby caecum and proximal colon combined was 25% longer in animals maintained on the pelleted diet compared with those maintained on forage. Our data suggest that food particle size may be directly involved in controlling the size of the post-gastric alimentary tract in tammar wallabies, and thus in their diet choice and nutritional ecology. Notably, this is the first study that links phenotypic plasticity of the gut directly to diet in a marsupial and we conclude that the tammar wallaby is an excellent model for exploring the causes and consequences of digestive plasticity in macropodid marsupials

Recent advances in marburgvirus research [version 1; peer review: 3 approved]

Marburgviruses are closely related to ebolaviruses and cause a devastating disease in humans. In 2012, we published a comprehensive review of the first 45 years of research on marburgviruses and the disease they cause, ranging from molecular biology to ecology. Spurred in part by the deadly Ebola virus outbreak in West Africa in 2013–2016, research on all filoviruses has intensified. Not meant as an introduction to marburgviruses, this article instead provides a synopsis of recent progress in marburgvirus research with a particular focus on molecular biology, advances in animal modeling, and the use of Egyptian fruit bats in infection experiments

Cloning and expression of feline colony stimulating factor receptor (CSF-1R) and analysis of the species specificity of stimulation by colony stimulating factor-1 (CSF-1) and interleukin-34 (IL-34).

AbstractColony stimulating factor (CSF-1) and its receptor, CSF-1R, have been previously well studied in humans and rodents to dissect the role they play in development of cells of the mononuclear phagocyte system. A second ligand for the CSF-1R, IL-34 has been described in several species. In this study, we have cloned and expressed the feline CSF-1R and examined the responsiveness to CSF-1 and IL-34 from a range of species. The results indicate that pig and human CSF-1 and human IL-34 are equally effective in cats, where both mouse CSF-1 and IL-34 are significantly less active. Recombinant human CSF-1 can be used to generate populations of feline bone marrow and monocyte derived macrophages that can be used to further dissect macrophage-specific gene expression in this species, and to compare it to data derived from mouse, human and pig. These results set the scene for therapeutic use of CSF-1 and IL-34 in cats

Coleoptera of Canada

The beetle fauna of Canada was assessed, including estimates of yet unreported diversity using information from taxonomists and COI sequence clusters in a BOLD (Barcode of Life Datasystems) COI dataset comprising over 77,000 Canadian records. To date, 8302 species of Coleoptera have been recorded in Canada, a 23% increase from the first assessment in 1979. A total of 639 non-native beetle species have become established in Canada, with most species in the Staphylinidae (153 spp.), Curculionidae (107 spp.), Chrysomelidae (56 spp.) and Carabidae (55 spp.). Based on estimates from the taxonomic community and our BOLD dataset, we estimate that slightly more than 1000 beetle species remain to be reported from Canada, either as new records or undescribed species. Renewed enthusiasm toward and financial support for surveys, especially in the central and western provinces of Canada will be critical for detecting, documenting and describing these species. The Barcode of Life database is still far from comprehensive for Canadian Coleoptera but substantial progress has been made and the number of Barcode Index Numbers (BINs) (as candidate species) has reached nearly 70% of the number of species reported from Canada. Comparison of BINs to observed species in a group of Canadian Staphylinidae suggests that BINs may provide a good estimate of species diversity within the beetles. Histeridae is a diverse family in Canada that is notably underrepresented in BOLD. Families such as Mordellidae, Scraptiidae, Latridiidae, Ptiliidae and Scirtidae are poorly known taxonomically in Canada and are represented in our BOLD dataset by many more BINs than recorded species

David Hume on Banking and Hoarding

David Hume opposes banks and favors hoarding. The only bank he reluctantly approves of is a public, 100% reserve bank. Other banks increase money supply and prices, hindering exports and economic growth. For Hume, a 100% reserve public bank would lead to ‘‘the destruction of paper-credit’’ ([1752] 1985, p. 285), fostering economic growth instead by preventing inflation. Additionally, a 100% reserve bank hoards a large quantity of gold and silver, which is available in case of national emergency

The Prosensory Function of Sox2 in the Chicken Inner Ear Relies on the Direct Regulation of Atoh1

The proneural gene Atoh1 is crucial for the development of inner ear hair cells and it requires the function of the transcription factor Sox2 through yet unknown mechanisms. In the present work, we used the chicken embryo and HEK293T cells to explore the regulation of Atoh1 by Sox2. The results show that hair cells derive from Sox2-positive otic progenitors and that Sox2 directly activates Atoh1 through a transcriptional activator function that requires the integrity of Sox2 DNA binding domain. Atoh1 activation depends on Sox transcription factor binding sites (SoxTFBS) present in the Atoh1 3′ enhancer where Sox2 directly binds, as shown by site directed mutagenesis and chromatin immunoprecipitation (ChIP). In the inner ear, Atoh1 enhancer activity is detected in the neurosensory domain and it depends on Sox2. Dominant negative competition (Sox2HMG-Engrailed) and mutation of the SoxTFBS abolish the reporter activity in vivo. Moreover, ChIP assay in isolated otic vesicles shows that Sox2 is bound to the Atoh1 enhancer in vivo. However, besides activating Atoh1, Sox2 also promotes the expression of Atoh1 negative regulators and the temporal profile of Atoh1 activation by Sox2 is transient suggesting that Sox2 triggers an incoherent feed-forward loop. These results provide a mechanism for the prosensory function of Sox2 in the inner ear. We suggest that sensory competence is established early in otic development through the activation of Atoh1 by Sox2, however, hair cell differentiation is prevented until later stages by the parallel activation of negative regulators of Atoh1 function