The interferon-stimulated gene IFITM3 restricts West Nile virus infection and pathogenesis

The interferon-induced transmembrane protein (IFITM) family of proteins inhibit infection of several different enveloped viruses in cell culture by virtue of their ability to restrict entry and fusion from late endosomes. As few studies have evaluated the importance of Ifitm3 in vivo in restricting viral pathogenesis, we investigated its significance as an antiviral gene against West Nile virus (WNV), an encephalitic flavivirus, in cells and mice. Ifitm3(−/−) mice were more vulnerable to lethal WNV infection, and this was associated with greater virus accumulation in peripheral organs and central nervous system tissues. As no difference in viral burden in the brain or spinal cord was observed after direct intracranial inoculation, Ifitm3 likely functions as an antiviral protein in nonneuronal cells. Consistent with this, Ifitm3(−/−) fibroblasts but not dendritic cells resulted in higher yields of WNV in multistep growth analyses. Moreover, transcomplementation experiments showed that Ifitm3 inhibited WNV infection independently of Ifitm1, Ifitm2, Ifitm5, and Ifitm6. Beyond a direct effect on viral infection in cells, analysis of the immune response in WNV-infected Ifitm3(−/−) mice showed decreases in the total number of B cells, CD4(+) T cells, and antigen-specific CD8(+) T cells. Finally, bone marrow chimera experiments demonstrated that Ifitm3 functioned in both radioresistant and radiosensitive cells, as higher levels of WNV were observed in the brain only when Ifitm3 was absent from both compartments. Our analyses suggest that Ifitm3 restricts WNV pathogenesis likely through multiple mechanisms, including the direct control of infection in subsets of cells. IMPORTANCE As part of the mammalian host response to viral infections, hundreds of interferon-stimulated genes (ISGs) are induced. The inhibitory activity of individual ISGs varies depending on the specific cell type and viral pathogen. Among ISGs, the genes encoding interferon-induced transmembrane protein (IFITM) have been reported to inhibit multiple families of viruses in cell culture. However, few reports have evaluated the impact of IFITM genes on viral pathogenesis in vivo. In this study, we characterized the antiviral activity of Ifitm3 against West Nile virus (WNV), an encephalitic flavivirus, using mice with a targeted gene deletion of Ifitm3. Based on extensive virological and immunological analyses, we determined that Ifitm3 protects mice from WNV-induced mortality by restricting virus accumulation in peripheral organs and, subsequently, in central nervous system tissues. Our data suggest that Ifitm3 restricts WNV pathogenesis by multiple mechanisms and functions in part by controlling infection in different cell types

Effects of Organic and Inorganic Fertilizers on Marigold Growth and Flowering

Two experiments were conducted to evaluate the growth and flowering responses of greenhouse-grown French marigold (Tagetes patula L. ‘Janie Deep Orange’) to two non-composted broiler chicken litter-based organic fertilizers, 4-2-2 and 3-3-3, and one commonly used synthetic controlled-release fertilizer, 14-14-14. In both experiments, fertilizer 4-2-2 was applied at four rates of 1%, 2%, 4%, and 6% (by volume); 3-3-3 was applied at four rates of 1.34%, 2.67%, 5.34%, and 8.0% (by volume); and 14-14-14 was applied at rates of 0.99, 1.98, 3.96, and 5.94 kg·m−3. In general, substrate containing different rates and types of fertilizers had a pH within the recommended range of 5.0 to 6.5. Electrical conductivity (EC) was similar among substrates containing different rates of 14-14-14; however, EC increased with increasing fertilizer rate for substrates containing 4-2-2 and 3-3-3. Substrate EC within each treatment was generally higher earlier in the experiment. For the fertilizer rates used in these two experiments, increasing 14-14-14 fertilizer rate increased plant growth and flowering performance. However, low to intermediate rates of 4-2-2 and 3-3-3 in general produced the highest plant growth index, shoot dry weight, number of flowers per plant, total flower dry weight, and root rating. Plants grown at high rates of 4-2-2 and 3-3-3 showed symptoms associated with excessive fertilization. Plant tissue nitrogen (N), phosphorus (P), and potassium (K) concentrations increased linearly or quadratically with increasing fertilizer rates for all three fertilizers. In general, plants receiving 4-2-2 and 3-3-3 had higher concentrations of N, P, and K than plants receiving 14-14-14. Results from this study indicated that broiler litter-based 4-2-2 and 3-3-3 have the potential to be used as organic fertilizer sources for container production of marigolds in greenhouses. However, growers need to be cautious with the rate applied. Because different crops may respond differently to these natural fertilizers, it is important for growers to test any new fertilizers before incorporating them into their production practices

The applicability of physical optics in the millimetre and sub-millimetre spectral region. Part II: Application to a three-component model of ice cloud and its evaluation against the bulk single-scattering properties of various other aggregate models

The bulk single-scattering properties of various randomly oriented aggregate ice crystal models are com- pared and contrasted at a number of frequencies between 89 and 874 GHz. The model ice particles consist of the ten-branched plate aggregate, five-branched plate aggregate, eight-branched hexagonal aggregate, Voronoi ice aggregate, six-branched hollow bullet rosette, hexagonal column of aspect ratio unity, and the ten-branched hexagonal aggregate. The bulk single-scattering properties of the latter two ice particle models have been calculated using the light scattering methods described in Part I, which represent the two most extreme members of an ensemble model of cirrus ice crystals. In Part I, it was shown that the method of physical optics could be combined with the T-matrix at a size parameter of about 18 to compute the bulk integral ice optical properties and the phase function in the microwave to sufficient ac- curacy to be of practical value. Here, the bulk single-scattering properties predicted by the two ensemble model members and the Voronoi model are shown to generally bound those of all other models at fre- quencies between 89 and 874 GHz, thus representing a three-component model of ice cloud that can be generally applied to the microwave, rather than using many differing ice particle models. Moreover, the Voronoi model and hollow bullet rosette scatter similarly to each other in the microwave. Furthermore, from the various comparisons, the importance of assumed shapes of the particle size distribution as well as cm-sized ice aggregates is demonstrated.Peer reviewedFinal Accepted Versio

Dark matter annihilation and non-thermal Sunyaev-Zel'dovich effect: II. dwarf spheroidal galaxy

We calculate the CMB temperature distortion due to the energetic electrons and positrons produced by dark matter annihilation (Sunyaev-Zel'dovich effect), in dwarf spheroidal galaxies (dSphs). In the calculation we have included two important effects which were previously ignored. First we show that the electron-positron pairs with energy less than GeV, which were neglected in previous calculation, could contribute a significant fraction of the total signal. Secondly we also consider the full effects of diffusion loss, which could significantly reduce the density of electron-positron pairs at the center of cuspy halos. For neutralinos, we confirm that detecting such kind of SZ effect is beyond the capability of the current or even the next generation experiments. In the case of light dark matter (LDM) the signal is much larger, but even in this case it is only marginally detectable with the next generation of experiment such as ALMA. We conclude that similar to the case of galaxy clusters, in the dwarf galaxies the SZ_2DM} effect is not a strong probe of DM annihilations.Comment: 22 pages, 9 figures, version accepted by JCA

Gamma rays from dark matter annihilation in the Draco and observability at ARGO

The CACTUS experiment recently observed a gamma ray excess above 50 GeV from the direction of the Draco dwarf spheroidal galaxy. Considering that Draco is dark matter dominated the gamma rays may be generated through dark matter annihilation in the Draco halo. In the framework of the minimal supersymmetric extension of the standard model we explore the parameter space to account for the gamma ray signals at CACTUS. We find that the neutralino mass is constrained to be approximately in the range between 100 GeV ~ 400 GeV and a sharp central cuspy of the dark halo profile in Draco is necessary to explain the CACTUS results. We then discuss further constraints on the supersymmetric parameter space by observations at the ground based ARGO detector. It is found that the parameter space can be strongly constrained by ARGO if no excess from Draco is observed above 100 GeV.Comment: 15 pages, 4 figure

Detecting the dark matter annihilation at the ground EAS detectors

In this paper we study the possibility of detecting gamma rays from dark matter annihilation in the subhalos of the Milky Way by the ground based EAS detectors within the frame of the minimal supersymmetric standard model. Based on the Monte Carlo simulation we also study the properties of two specific EAS detectors, the ARGO and HAWC, and the sensitivities of these detectors on the detection of dark matter annihilation. We find the ground EAS detectors have the possibility to observe such signals. Conversely if no signal observed we give the constraints on the supersymmetric parameter space, which however depends on the subhalos properties.Comment: 23 pages, 9 figures, accepted by NP

Questionnaire study to gain an insight into the manufacturing and fitting process of artificial eyes in children: an ocularist perspective

Purpose To gain an insight into the manufacturing and fitting of artificial eyes in children and potential improvements to the process. Method An online qualitative survey was distributed to 39 ocularists/prosthetists in Europe and Canada. Participants were recruited through purposive sampling, specifically maximum variation sampling from the researcher’s contacts and an online search. Results The findings highlighted the current impression technique as being the most difficult yet most important part of the current process for both the ocularist and child patient. Negatively affecting obtaining a good impression, the child patients distress can be reduced by their parents by providing encouragement, reassurance, practicing the insertion and removal of the artificial eye and being matter of fact. Whilst improvements to the current process provided mixed views, the incorporation of current technology was perceived as not being able to meet the requirements to produce aesthetically pleasing artificial eyes. Conclusion The current artificial eye process can be seen as an interaction with its success being dependent on the child patient’s acceptance and adjustment which is dependent on the factors associated to the process. Investigation into the needs of the patient and whether technology can improve the process are the next steps in its advancement

Determining the Topic Evolution and Sentiment Polarity for Albinism in a Chinese Online Health Community: Machine Learning and Social Network Analysis

There are more than 6000 rare diseases in existence today, with the number of patients with these conditions rapidly increasing. Most research to date has focused on the diagnosis, treatment, and development of orphan drugs, while few studies have examined the topics and emotions expressed by patients living with rare diseases on social media platforms, especially in online health communities (OHCs). Objective This study aimed to determine the topic categorizations and sentiment polarity for albinism in a Chinese OHC, Baidu Tieba, using multiple methods. The OHC was deeply mined using topic mining, social network analysis, and sentiment polarity analysis. Through these methods, we determined the current situation of community construction, identifying the ongoing needs and problems experienced by people with albinism in their daily lives. Methods We used the albinism community on the Baidu Tieba platform as the data source in this study. Term frequency–inverse document frequency, latent dirichlet allocation models, and naive Bayes were employed to mine the various topic categories. Social network analysis, which was completed using the Gephi tool, was employed to analyze the evolution of the albinism community. Sentiment polarity analysis was performed using a long short-term memory algorithm. Results We identified 8 main topics discussed in the community: daily sharing, family, interpersonal communication, social life and security, medical care, occupation and education, beauty, and self-care. Among these topics, daily sharing represented the largest proportion of the discussions. From 2012 to 2019, the average degree and clustering coefficient of the albinism community continued to decline, while the network center transferred from core communities to core users. A total of 68.43% of the corpus was emotional, with 35.88% being positive and 32.55% negative. There were statistically significant differences in the distribution of sentiment polarity between topics (P Conclusions The study reveals insights into the emotions expressed by people with albinism in the Chinese OHC, Baidu Tieba, providing health care practitioners with greater appreciation of the current emotional support needed by patients and the patient experience. Current OHCs do not exert enough influence due to limited effective organization and development. Health care sectors should take greater advantage of OHCs to support vulnerable patients with rare diseases to meet their evidence-based needs. </jats:sec

Mechanical Stress Inference for Two Dimensional Cell Arrays

Many morphogenetic processes involve mechanical rearrangement of epithelial tissues that is driven by precisely regulated cytoskeletal forces and cell adhesion. The mechanical state of the cell and intercellular adhesion are not only the targets of regulation, but are themselves likely signals that coordinate developmental process. Yet, because it is difficult to directly measure mechanical stress {\it in vivo} on sub-cellular scale, little is understood about the role of mechanics of development. Here we present an alternative approach which takes advantage of the recent progress in live imaging of morphogenetic processes and uses computational analysis of high resolution images of epithelial tissues to infer relative magnitude of forces acting within and between cells. We model intracellular stress in terms of bulk pressure and interfacial tension, allowing these parameters to vary from cell to cell and from interface to interface. Assuming that epithelial cell layers are close to mechanical equilibrium, we use the observed geometry of the two dimensional cell array to infer interfacial tensions and intracellular pressures. Here we present the mathematical formulation of the proposed Mechanical Inverse method and apply it to the analysis of epithelial cell layers observed at the onset of ventral furrow formation in the {\it Drosophila} embryo and in the process of hair-cell determination in the avian cochlea. The analysis reveals mechanical anisotropy in the former process and mechanical heterogeneity, correlated with cell differentiation, in the latter process. The method opens a way for quantitative and detailed experimental tests of models of cell and tissue mechanics