Host cell specificity of minute virus of mice in the developing mouse embryo

Productive infection by the murine autonomous parvovirus minute virus of mice (MVM) depends on a dividing cell population and its differentiation state. We have extended the in vivo analysis of the MVM host cell type range into the developing embryo by in utero inoculation followed by further gestation. The fibrotropic p strain (MVMp) and the lymphotropic i strain (MVMi) did not productively infect the early mouse embryo but were able to infect overlapping sets of cell types in the mid- or late-gestation embryo. Both MVMp and MVMi infected developing bone primordia, notochord, central nervous system, and dorsal root ganglia. MVMp exhibited extensive infection in fibroblasts, in the epithelia of lung and developing nose, and, to a lesser extent, in the gut. MVMi also infected endothelium. The data indicated that the host ranges of the two MVM strains consist of overlapping sets of cell types that are broader than previously known from neonate and in vitro infection experiments. The correlation between MVM host cell types and the cell types that activate the transgenic P4 promoter is consistent with the hypothesis that activation of the incoming viral P4 promoter by the host cell is one of the host range determinants of MVM.     

The effect of short, high intensity magnetic field pulses on the healing of skin wounds in rats

The object of this study was to examine the effect of high intensity, short duration pulsed electromagnetic fields (PEMF) on the healing of full thickness skin wounds in rats. Full thickness skin wounds were surgically created in two groups of Sprague-Dawley male rats. The rats were randomly divided into two groups, each containing 20 rats. Animals in the treatment group received treatments with the PEMF device on day 0, 3, 7, 9, 12, 14, 17, and 22, while the rats in the control group were subjected to the same procedure, but with the PEMF device not activated. Photographs of the surgically created wounds were obtained on day 0, 3, 7, 9, 12, 14, 17, and 22. Wound contraction (WC), wound epithelialization (WE), non-healed wound, and contraction-epithelialization (CE) ratio were calculated for each wound. No significant difference was found between the two groups for the parameters of WC, WE, non-healed wound, and CE ratio. A significant group x time interaction was found for WE and CE ratio. This type of PEMF did not have a significantly beneficial effect on wound healing. Wounds in the PEMF treated group were relatively less contracted and showed a compensatory increase in epithelialization in the early stages of wound repair.     

A novel septal protein of multicellular heterocystous cyanobacteria is associated with the divisome

Cyanobacteria are unique among the eubacteria as they possess a hybrid Gram phenotype, having an outer membrane but also a comparably thick peptidoglycan sheet. Furthermore, the cyanobacterial divisome includes proteins specific for both the Gram types as well as cyanobacteria-specific proteins. Cells in multicellular cyanobacteria share a continuous periplasm and their cytoplasms are connected by septal junctions that enable communication between cells in the filament. The localization of septal junction proteins depends on interaction with the divisome, however additional yet unknown proteins may be involved in this process. Here, we characterized Alr3364 (termed SepI), a novel septal protein that interacts with the divisome in the multicellular heterocystous cyanobacterium Anabaena sp. strain PCC 7120. SepI localized to the Z-ring and the intercellular septa but did not interact with FtsZ. Instead, SepI interacted with the divisome proteins ZipN, SepF and FtsI and with the septal protein SepJ. The inactivation of sepI led to a defect in cell filament integrity, colony and cell morphology, septum size, nanopore formation and peptidoglycan biogenesis, and inability to differentiate heterocysts. Our results show that SepI plays a role in intercellular communication and furthermore indicate that SepI functions in the coordination of septal junction localization during cell division.     

Work that body: fin and body movements determine herbivore feeding performance within the natural reef environment

Herbivorous fishes form a keystone component of reef ecosystems, yet the functional mechanisms underlying their feeding performance are poorly understood. In water, gravity is counter-balanced by buoyancy, hence fish are recoiled backwards after every bite they take from the substrate. To overcome this recoil and maintain contact with the algae covered substrate, fish need to generate thrust while feeding. However, the locomotory performance of reef herbivores in the context of feeding has hitherto been ignored. We used a three-dimensional high-speed video system to track mouth and body kinematics during in situ feeding strikes of fishes in the genus Zebrasoma, while synchronously recording the forces exerted on the substrate. These herbivores committed stereotypic and coordinated body and fin movements when feeding off the substrate and these movements determined algal biomass removed. Specifically, the speed of rapidly backing away from the substrate was associated with the magnitude of the pull force and the biomass of algae removed from the substrate per feeding bout. Our new framework for measuring biting performance in situ demonstrates that coordinated movements of the body and fins play a crucial role in herbivore foraging performance and may explain major axes of body and fin shape diversification across reef herbivore guilds.     

Colonization dynamics of Pantoea agglomerans in the wheat root habitat

Plants are colonized by microbial communities that have diverse implications for plant development and health. The establishment of a stable plant–bacteria interaction depends on a continuous coexistence over generations. Transmission via the seed is considered as the main route for vertical inheritance of plant-associated bacteria. Nonetheless, the ecological principles that govern the plant colonization by seed endophytes remain understudied. Here we quantify the contribution of arrival time and colonization history to bacterial colonization of the wheat root. Establishing a common seed endophyte, Pantoea agglomerans, and wheat as a model system enabled us to document bacterial colonization of the plant roots during the early stages of germination. Using our system, we estimate the carrying capacity of the wheat roots as 10⁸ cells g⁻¹, which is robust among individual plants and over time. Competitions in planta reveal a significant advantage of early incoming colonizers over late-incoming colonizers. Priming for the wheat environment had little effect on the colonizer success. Our experiments thus provide empirical data on the root colonization dynamics of a seed endophyte. The persistence of seed endophyte bacteria with the plant population over generations may contribute to the stable transmission that is one route for the evolution of a stable host-associated lifestyle.     

Quantitative proteomic analysis after neuroprotective MyD88 inhibition in the retinal degeneration 10 mouse

Progressive photoreceptor death occurs in blinding diseases such as retinitis pigmentosa. Myeloid differentiation primary response protein 88 (MyD88) is a central adaptor protein for innate immune system Toll-like receptors (TLR) and induces cytokine secretion during retinal disease. We recently demonstrated that inhibiting MyD88 in mouse models of retinal degeneration led to increased photoreceptor survival, which was associated with altered cytokines and increased neuroprotective microglia. However, the identity of additional molecular changes associated with MyD88 inhibitor-induced neuroprotection is not known. In this study, we used isobaric tags for relative and absolute quantification (iTRAQ) labelling followed by LC-MS/MS for quantitative proteomic analysis on the rd10 mouse model of retinal degeneration to identify protein pathways changed by MyD88 inhibition. Quantitative proteomics using iTRAQ LC-MS/MS is a high-throughput method ideal for providing insight into molecular pathways during disease and experimental treatments. Forty-two proteins were differentially expressed in retinas from mice treated with MyD88 inhibitor compared with control. Notably, increased expression of multiple crystallins and chaperones that respond to cellular stress and have anti-apoptotic properties was identified in the MyD88-inhibited mice. These data suggest that inhibiting MyD88 enhances chaperone-mediated retinal protection pathways. Therefore, this study provides insight into molecular events contributing to photoreceptor protection from modulating inflammation.     

CXCR4 or CXCR7 antagonists treat endometriosis by reducing bone marrow cell trafficking

Adult stem cells have a major role in endometrial physiology, including remodelling and repair. However, they also have a critical role in the development and progression of endometriosis. Bone marrow‐derived stem cells engraft eutopic endometrium and endometriotic lesions, differentiating to both stromal and epithelial cell fates. Using a mouse bone marrow transplantation model, we show that bone marrow‐derived cells engrafting endometriosis express CXCR4 and CXCR7. Targeting either receptor by the administration of small molecule receptor antagonists AMD3100 or CCX771, respectively, reduced BM‐derived stem cell recruitment into endometriosis implants. Endometriosis lesion size was decreased compared to vehicle controls after treatment with each antagonist in both an early growth and established lesion treatment model. Endometriosis lesion size was not effected when the local effects of CXCL12 were abrogated using uterine‐specific CXCL12 null mice, suggesting an effect primarily on bone marrow cell migration rather than a direct endometrial effect. Antagonist treatment also decreased hallmarks of endometriosis physiopathology such as pro‐inflammatory cytokine production and vascularization. CXCR4 and CXCR7 antagonists are potential novel, non‐hormonal therapies for endometriosis.     

Phase-dependent immune evasion of herpesviruses

Viruses employ various modes to evade immune detection. Two possible evasion modes are a reduction of the number of epitopes presented and the mimicry of host epitopes. The immune evasion efforts are not uniform among viral proteins. The number of epitopes in a given viral protein and the similarity of the epitopes to host peptides can be used as a measure of the viral attempts to hide this protein. Using bioinformatics tools, we here present a genomic analysis of the attempts of four human herpesviruses (herpes simplex virus type 1-human herpesvirus 1, Epstein-Barr virus-human herpesvirus 4, human cytomegalovirus-human herpesvirus 5, and Kaposi's sarcoma-associated herpesvirus-human herpesvirus 8) and one murine herpesvirus (murine herpesvirus 68) to escape from immune detection. We determined the full repertoire of CD8 T-lymphocyte epitopes presented by each viral protein and show that herpesvirus proteins present many fewer epitopes than expected. Furthermore, the epitopes that are presented are more similar to host epitopes than are random viral epitopes, minimizing the immune response. We defined a score for the size of the immune repertoire (the SIR score) based on the number of epitopes in a protein. The numbers of epitopes in proteins expressed in the latent and early phases of infection were significantly smaller than those in proteins expressed in the lytic phase in all tested viruses. The latent and immediate-early epitopes were also more similar to host epitopes than were lytic epitopes. A clear trend emerged from the analysis. In general, herpesviruses demonstrated an effort to evade immune detection. However, within a given herpesvirus, proteins expressed in phases critical to the fate of infection (e.g., early lytic and latent) evaded immune detection more than all others. The application of the SIR score to specific proteins allows us to quantify the importance of immune evasion and to detect optimal targets for immunotherapy and vaccine development.