2,585 research outputs found

    Complete genome sequence of Torque teno indri virus 1, a novel anellovirus in blood from a free-living lemur

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    ABSTRACT We identified Torque teno indri virus 1 (TTIV1), the first anellovirus in a free-living lemur ( Indri indri ). The complete circular 2,572-nucleotide (nt) TTIV1 genome is distantly related to torque teno sus virus. Phylogenetic and sequence analyses support TTIV1 as a putative member of a new genus within the Anelloviridae family. </jats:p

    Long term in vitro expansion of epithelial stem cells enabled by pharmacological inhibition of PAK1-ROCK-Myosin II and TGF-β signaling

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    Summary: Despite substantial self-renewal capability in vivo, epithelial stem and progenitor cells located in various tissues expand for a few passages in vitro in feeder-free condition before they succumb to growth arrest. Here, we describe the EpiX method, which utilizes small molecules that inhibit PAK1-ROCK-Myosin II and TGF-β signaling to achieve over one trillion-fold expansion of human epithelial stem and progenitor cells from skin, airway, mammary, and prostate glands in the absence of feeder cells. Transcriptomic and epigenomic studies show that this condition helps epithelial cells to overcome stresses for continuous proliferation. EpiX-expanded basal epithelial cells differentiate into mature epithelial cells consistent with their tissue origins. Whole-genome sequencing reveals that the cells retain remarkable genome integrity after extensive in vitro expansion without acquiring tumorigenicity. EpiX technology provides a solution to exploit the potential of tissue-resident epithelial stem and progenitor cells for regenerative medicine. : Zhang et al. screen a small-molecule collection and find that pharmacologic inhibition of TGF-β and PAK1-ROCK-Myosin II, in low calcium conditions, supports extended expansion of epithelial stem cells in 2D format. This approach enhances the potential of tissue-resident epithelial stem cells for cell therapy. Keywords: epithelial stem and progenitor cells, cell culture method, TGF-β, PAK1/ROCK/Myosin II, feeder-free, regenerative medicine, cell therap

    Species-specific transmission of novel picornaviruses in lemurs

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    The roles of host genetics versus exposure and contact frequency in driving cross-species transmission remain the subject of debate. Here, we used a multitaxon lemur collection at the Saint Louis Zoo in the United States as a model to gain insight into viral transmission in a setting of high interspecies contact. Lemurs are a diverse and understudied group of primates that are highly endangered. The speciation of lemurs, which are endemic to the island of Madagascar, occurred in geographic isolation apart from that of continental African primates. Although evidence of endogenized viruses in lemur genomes exists, no exogenous viruses of lemurs have been described to date. Here we identified two novel picornaviruses in fecal specimens of ring-tailed lemurs (Lemur catta) and black-and-white ruffed lemurs (Varecia variegata). We found that the viruses were transmitted in a species-specific manner (lesavirus 1 was detected only in ring-tailed lemurs, while lesavirus 2 was detected only in black-and-white ruffed lemurs). Longitudinal sampling over a 1-year interval demonstrated ongoing infection in the collection. This was supported by evidence of viral clearance in some animals and new infections in previously uninfected animals, including a set of newly born triplets that acquired the infection. While the two virus strains were found to be cocirculating in a mixed-species exhibit of ring-tailed lemurs, black-and-white ruffed lemurs, and black lemurs, there was no evidence of cross-species transmission. This suggests that despite high-intensity contact, host species barriers can prevent cross-species transmissions of these viruses. IMPORTANCE Up to 75% of emerging infectious diseases in humans today are the result of zoonotic transmission. However, a challenge in understanding transmission dynamics has been the limited models of cross-species transmission. Zoos provide a unique opportunity to explore parameters defining viral transmission. We demonstrated that ongoing virus transmission in a mixed lemur species exhibit was species specific. This suggests that despite high contact intensity, host species barriers contribute to protection from cross-species transmission of these viruses. While the combinations of species might differ, most zoological parks worldwide commonly feature mixed-species exhibits. Collectively, this report demonstrates a widely applicable approach toward understanding infectious disease transmission

    Endogenization of a prosimian retrovirus during lemur evolution

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    Studies of viruses that coevolved with lemurs provide an opportunity to understand the basal traits of primate viruses and provide an evolutionary context for host-virus interactions. Germline integration of endogenous retroviruses (ERVs) are fossil evidence of past infections. Hence, characterization of novel ERVs provides insight into the ancient precursors of extant viruses and the evolutionary history of their hosts. Here, we report the discovery of a novel endogenous retrovirus present in the genome of a lemur, Coquerel\u27s sifaka

    Spatiotemporal complexity of a ratio-dependent predator-prey system

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    In this paper, we investigate the emergence of a ratio-dependent predator-prey system with Michaelis-Menten-type functional response and reaction-diffusion. We derive the conditions for Hopf, Turing and Wave bifurcation on a spatial domain. Furthermore, we present a theoretical analysis of evolutionary processes that involves organisms distribution and their interaction of spatially distributed population with local diffusion. The results of numerical simulations reveal that the typical dynamics of population density variation is the formation of isolated groups, i.e., stripelike or spotted or coexistence of both. Our study shows that the spatially extended model has not only more complex dynamic patterns in the space, but also chaos and spiral waves. It may help us better understand the dynamics of an aquatic community in a real marine environment.Comment: 6pages, revtex

    Influenza virus differentially activates mTORC1 and mTORC2 signaling to maximize late stage replication

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    <div><p>Influenza A virus usurps host signaling factors to regulate its replication. One example is mTOR, a cellular regulator of protein synthesis, growth and motility. While the role of mTORC1 in viral infection has been studied, the mechanisms that induce mTORC1 activation and the substrates regulated by mTORC1 during influenza virus infection have not been established. In addition, the role of mTORC2 during influenza virus infection remains unknown. Here we show that mTORC2 and PDPK1 differentially phosphorylate AKT upon influenza virus infection. PDPK1-mediated phoshorylation of AKT at a distinct site is required for mTORC1 activation by influenza virus. On the other hand, the viral NS1 protein promotes phosphorylation of AKT at a different site via mTORC2, which is an activity dispensable for mTORC1 stimulation but known to regulate apoptosis. Influenza virus HA protein and down-regulation of the mTORC1 inhibitor REDD1 by the virus M2 protein promote mTORC1 activity. Systematic phosphoproteomics analysis performed in cells lacking the mTORC2 component Rictor in the absence or presence of Torin, an inhibitor of both mTORC1 and mTORC2, revealed mTORC1-dependent substrates regulated during infection. Members of pathways that regulate mTORC1 or are regulated by mTORC1 were identified, including constituents of the translation machinery that once activated can promote translation. mTORC1 activation supports viral protein expression and replication. As mTORC1 activation is optimal midway through the virus life cycle, the observed effects on viral protein expression likely support the late stages of influenza virus replication when infected cells undergo significant stress.</p></div

    The influence of palatal harvesting technique on the donor site vascular injury: A splitâ mouth comparative cadaver study

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    BackgroundThe aim of this study was to evaluate the influence of two harvesting approaches on the donor site vascular injury.MethodsA splitâ mouth cadaver study was designed on 21 fresh donor heads. Every hemiâ palate was assigned to receive the trapâ door harvesting technique (TDT) or the epithelialized free gingival graft harvesting technique (FGGT). A soft tissue graft was harvested from each side for histology analyses. Betadine solution was used to inject the external carotid artery and a collagen sponge was positioned over the harvested area to compare the amount of â leakage.â ResultsThe mean leakage observed was 16.56 ± 3.01 µL in the FGGTâ harvested sites, and 69.21 ± 7.08 µL for the TDT group, a ratio of 4.18 (P < 0.01). Regression analyses demonstrated a trend for more leakage at thinner palatal sites for the FGGT group (P = 0.09), and a statistically significant correlation for the TDTâ harvest sites (P = 0.02). Additionally, a shallow palatal vault height (PVH) was associated with a higher leakage in both harvesting groups (P = 0.02). The histomorphometric analyses revealed that grafts harvested with TDT exhibited a significantly higher mean number of medium (ø = 0.1 to 0.5 mm, P = 0.03), and large vessels (ø â ¥ 0.5 mm, P = 0.02).ConclusionsWithin the limitations of the present research, the TDT resulted in a significantly higher leakage than the FGGT, which was also correlated with the histology analyses where a greater number of medium and large vessels were observed in the harvested grafts.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153658/1/jper10394.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153658/2/jper10394_am.pd
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